Podcast appearances and mentions of paul wang

Send us a textWhat if awe begins with remembering? In this episode, co-hosts Belinda Liu and Omar Brownson are joined by Dr. Paul Wang to explore the seasonal shift from budding to blooming—and how the heart holds the wisdom to navigate both. Rooted in Daoist philosophy, plant medicine, and the Gratitude Blooming card of Simplicity, this conversation offers a gentle invitation to slow down, feel more, and choose what truly matters.Don't miss the guided somatic practice at the end of this episode to support your emotional resilience and heart-centered mindfulness this spring.

Send us a textHow might simplifying your focus create space for what truly matters to flourish in your life this spring? A delightful spring energy infuses this conversation as co-host Omar Brownson shares his transformative experience with the Ubuntu Climate Initiative in South Carolina's Gullah Geechee lowcountry. His beautiful poem "Purple Sarongs" captures the essence of gathering on historically significant land where Dr. King dreamed his "I Have a Dream" speech—a powerful setting for visioning 150 years into our collective future.The synchronicity of simplicity emerges as an unexpected through-line when co-host Belinda Liu reflects on her annual community spring equinox experience in Mount Shasta.  She picked the simplicity card in the opening ritual when exploring the threads between money, resources and exchanging in community.Dr. Paul Wang, our special guest for this season, illuminates Daoist cosmology's approach to seasonal change, explaining how April serves as an intentional transitional month and rite of passage towards flowering through the process of budding.  This cycle is an ideal time for us to reconnect with our values and honor what's shifting within and around us. He describes spring's budding energy as concentrated potential—focused rather than dispersed—and offers a powerful three-step simplification process: 1) essentialize core values, 2) eliminate what doesn't align, and 3) embrace what remains by braiding it into unity.When they collectively choose the Gratitude Blooming card represented by the Nasturtium flower with its theme of friendship, the conversation deepens around how self-friendship forms the foundation for authentic community connection. Omar visualizes this as a vessel—a "friendship" carrying us forward together through periods of growth and change. They reflect on how trust accelerates transformation, noting that "change moves at the speed of trust," and how the clearer we can envision possibilities beyond current challenges, the more effectively we can practice that world today.Join us for our first Gratitude Blooming retreats in Mt. Shasta and on the Big Island. Use this promo code to get 20% off your retreat ticket >> BIGTHANKSWhether you're seeking to navigate personal transitions, deepen your connection with natural cycles, or find community in uncertain times, our podcast and in-personal gatherings offer practical wisdom for concentrating your energy where it matters most. -------Create an intentional practice with your own Gratitude Blooming card deck, notecards, candle and much much more at our shop at www.gratitudeblooming.com. Your purchase helps us sustain this podcast, or you can also sponsor us here. Learn more about our co-hosts and special guest: Belinda Liu | Hestia Retreat Centers Omar Brownson | Trickster's Guide to Immortality on Substack Dr. Paul Wang | The Dao CenterIf you enjoyed this episode, please take a moment to leave us a 5-star rating and review. Your feedback is valuable to us and helps us grow. Share your thoughts and comments by emailing us at hello@gratitudeblooming.com. We love hearing from our listeners!

Advancements in arrhythmia care are transforming patient outcomes and reshaping clinical practices. Join Dr. Sanjiv Narayan, Professor of Medicine at Stanford University, and Dr. Paul Wang, Professor of Medicine and of Bioengineering at Stanford University, as they explore the evolving field of electrophysiology, highlighting the importance of early detection and best practices in the management of common electrical abnormalities. Discover how a patient-centered approach can enhance care and outcomes for those with irregular heart rhythms. Read Transcript CME Information: https://stanford.cloud-cme.com/medcastepisode99 Claim CE: https://stanford.cloud-cme.com/Form.aspx?FormID=3229

Send us a textWhat if we could harness the wisdom of nature to transform our lives? Join us as we explore this intriguing question with our esteemed guest, Dr. Paul Wang, whose expertise in Chinese medicine and Daoism guides us through the profound themes of grief, gratitude, and self-care. Reflecting on the recent natural disasters in Los Angeles, we delve into the crucial importance of aligning with nature and fostering a sense of collective well-being. Discover the tools of pausing, noticing, and community as we navigate the challenges of rebuilding and reimagining our connection with the environment.As we venture into the intriguing realm of cosmic and personal cycles, prepare to be captivated by the solar polar flip and its potential effects on our natural world. This cosmic event sets the stage for a broader conversation on life's small signals—those subtle cues that can have a significant impact if left unaddressed. With the help of the Gratitude Blooming Card deck, we reflect on the importance of friendship as a source of resilience and balance, drawing parallels to our personal experiences of feeling overwhelmed and the necessity of self-care to prevent burnout.We then transition into a vibrant exploration of friendship as an ecosystem, reflecting on the diversity of human experiences and the interconnectedness of our relationships. The colorful nasturtium flowers serve as a metaphor for the beauty and complexity of our communities, while ancient symbols like the Rod of Asclepius remind us of the healing power of companionship. As we embrace the sweetness and bitterness of life, we invite you to tune into your own seeds of intention, nurturing them as we all prepare for the growth and transformation that lies ahead. If you'd like to practice seasonal living with us to navigate change and challenge with more wholeness, sign up for our new online Change Well Series launching Feb 23 to Mar 16, 2025.  Together, we will embark on a special journey to prepare for the spring cycle through physical, mental, emotional and spiritual alchemy.  REGISTER HERE:https://www.gratitudeblooming.com/changewell-------Create an intentional practice with your own Gratitude Blooming card deck, notecards, candle and much much more at our shop at www.gratitudeblooming.com. Your purchase helps us sustain this podcast, or you can also sponsor us here. If you enjoyed this episode, please take a moment to leave us a 5-star rating and review. Your feedback is valuable to us and helps us grow. Share your thoughts and comments by emailing us at hello@gratitudeblooming.com. We love hearing from our listeners!

Send us a textDiscover the profound insights of seasonal living with the esteemed Dr. Paul Wang, whose extensive experience in martial, medical, and mystical practices illuminates the path to a life in harmony with nature's cycles. Join us as Dr. Wang reveals the art of dancing through life's changes, emphasizing the importance of aligning with the natural rhythms of birth, growth, maturation, and dormancy also known as spring, summer, fall and winter. Explore the necessity of stillness and the magic of connecting with one's center, as we reflect on the releasing time of fall. Together, we challenge the influences of technology and artificial light, urging a return to rest and the inner world.We also delve into the dynamic balance of yin and yang during seasonal transitions, examining its impact on our communities and personal relationships. Through the symbolism of nasturtium in the Gratitude Blooming Card deck, we invite you to embrace the darkness and the hidden treasures it can unveil in your life. As we navigate the powerful emotion of fear, Dr. Wang shares strategies to not only face it but thrive amidst uncertainty, drawing on astrological insights and the guiding intelligences of mind, intuition, and instinct. Finally, we celebrate the concept of fearless gratitude, underscoring the role of self-trust and inner confidence in personal transformation and resilience.-------Create an intentional practice with your own Gratitude Blooming card deck, notecards, candle and much much more at our shop at www.gratitudeblooming.com. Your purchase helps us sustain this podcast, or you can also sponsor us here. If you enjoyed this episode, please take a moment to leave us a 5-star rating and review. Your feedback is valuable to us and helps us grow. Share your thoughts and comments by emailing us at hello@gratitudeblooming.com. We love hearing from our listeners!

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Danielle Haanschoten, Hein Wellens and Associates aim to examine survival benefit of prophylactic implantable cardioversion defibrillator (ICD) implantation in early selected high-risk patients with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk primary PCI patients based on one of the following factors: Left ventricular ejection fraction (LVF) less than 30% within four days of STEMI, primary ventricular fibrillation, Killip class 2 or greater and/or TEMI flow less than three after PCI. ICD was implanted 30 to 60 days after MI, myocardial infarction, primary endpoint was all cause mortality three years of follow-up. The trial was prematurely ended after inclusion of 266 patients, 38% of the calculated sample size. Additional survival assessments was performed in February 2019 for the primary endpoint. A total of 266 patients, 78.2% male with a mean age of 60.8 years were enrolled. 131 were randomized to the ICD arm and 135 patients to the control arm. All cause mortality was significantly lower in the ICD group, five versus 13, hazard ratio of 0.37 after three years follow-up. Appropriate ICD therapy occurred in nine patients at three years follow-up, 5 within the first eight months after implantation. After median long-term follow-up of nine years, total mortality (18% versus 38%, hazard ratio of 0.58) and cardiac mortality (hazard ratio of 0.52) was significantly lower in the ICD group. Non-cardiac death was not significantly different between the groups. LVEF increased 10% or more in the 46.5% of patients during follow-up and the extent of improvement was similar in both study groups. The authors concluded that in this prematurely terminated and thus underpowered randomized trial early prophylactic ICD implantation demonstrated lower total and cardiac mortality in high-risk STEMI patients treated with primary PCI.   In our next paper Felipe Bisbal, Eva Benito and Associates aim to test the efficacy of ablating, cardiac magnetic resonance, CMR detected atrial fibrosis plus pulmonary vein isolation (PVI). This was an open label, parallel group, randomized controlled trial. Patients with symptomatic drug refractory AF paroxysmal or persistent undergoing first or repeat ablation were randomized one-to-one basis to receive PVI plus CMR-guided fibrosis ablation, the CMR group or PVI alone, the PVI alone group. The primary endpoint was a rate of recurrence greater than 30 seconds at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6 and 12 months. The analysis was conducted by intention to treat. In total 155 patients, 71% male, age 59, CHADS2-VASc 1.3, 54% paroxysmal AF were allocated to the PVI group alone (n=76) or CMR group(n=79). First ablation was performed in 80% and 71% in the PVI alone and CMR groups respectively. The mean atrial fibrosis burden was 12%, only approximately 50% of patients had fibrosis outside the pulmonary vein area. 100% and 99% of patients received the assigned intervention in the PVI alone and CMR group. Primary outcome was achieved in 21 patients (27.6%) in the PVI alone group and 22 patients (27.8%) in the CMR group (Odds ratio 0.01, P=0.976). There was no differences in the rate of adverse events, three in the CMR group and two in the PVI alone group. The authors concluded that a pragmatic ablation approach targeting CMR detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing AF ablation with low fibrosis burden.   In the next paper, Vivek Reddy and Associates tested a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. 15 subjects admitted for defibrillator implantation (ejection fraction≤35%) on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 hertz, 4 ms pulse width, and less than or equal to 20 milliamperes. Changes in the maximum positive dP/dt, the dP/dtMax indicated change in ventricular contractility. Of 15 enrolled patients, five were not studied due to equipment failure or abnormal pulmonary artery anatomy. In the remaining patients dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt, dP/dtMin, mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, the authors demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures.   In our next paper, Jorge Romero, Luigi Di Biase, and Associates, in their study investigated the incremental benefit of left atrial appendage electrical isolation (LAAEI) in patients undergoing catheter ablation for nonparoxysmal atrial fibrillation (AF). Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Authors identified 1842 patients who underwent catheter ablation for nonparoxysmal atrial fibrillation. Propensity score matching yielded 1092 patients, 546 with LAAEI, and 546 without LAAEI. At five years follow-up, overall freedom from all arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation (p

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries. In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies. In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection. In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation. In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; P

I speak with Singapore-based educator and artist Paul Wang about the way he dances, using line and color, across the page. Paul finds art in the middle of urban chaos and he paints it with dramatic colors and meandering lines. His composition is informed by his education in interior design and theatre production. He tries to tell a story with every piece, and that influences every artistic decision on the page - color and line, conflict and collaboration, work and play. Paul and Suhita Shirodkar have been running the aptly-named Sketching Play Lab since March, with participants from around the world meeting over Zoom. We talk about his work as an educator and urban-sketching instructor, the different ways he encourages people to approach their art practice to find joy, as well as the things he has learned from being in the USk community. Follow Paul's work on IG or visit his website to see his art + get info on the Sketching Play Lab. To see SneakyArt, visit my website, check out my IG or Linktree. Read a transcript of this conversation and find related links on sneakyartist.com/podcast. Support my work with a cup of coffee!

Paul J. Wang: Welcome to the monthly podcast, On the BEAT, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. Paul J. Wang: Albert Feeny and Associates used unsupervised machine learning of electrocardiogram [ECG] waveforms to identify cardiac resynchronization therapy [CRT] subgroups to differentiate outcomes beyond QRS duration and left bundle branch block. They retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis [PCA] dimensionality reduction obtained a 2-dimensional representation of pre-CRT 12-lead QRS waveforms. K-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified two patient subgroups [QRS PCA groups]. Vectorcardiographic QRS area was also calculated. They examined two primary outcomes: (1) composite endpoint of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction [LVEF] change after CRT. Compared to QRS PCA group 2 (n = 425), Group 1 (n=521) had a lower risk for achieving the composite endpoint (hazard ratio of 0.44, P < 0.001) and experienced greater mean LVEF improvement (11.1% versus 4.8%, P < 0.001), even among left bundle branch block patients with QRS duration, 150 milliseconds or greater (hazard ratio 0.45, P < 0.001; mean LVF change 12.5% versus 7.3%, P=0.001). A stratification scheme combining QRS area and QRS PCA group identified left bundle branch block patients with similar outcomes as non left bundle branch block patients (hazard ratio 1.32, mean difference LVEF change 0.8%). That stratification scheme also identified left bundle branch block patients with QRS duration less than 150 ms is comparable outcomes to left bundle branch patients with QRS duration 150 ms or greater (hazard ratio 0.93, mean difference in LVF change -0.2%). The authors concluded that unsupervised machine learning of ECG waveforms identified CRT subgroups with relevance beyond left bundle branch block and QRS duration. Paul J. Wang: In our next paper, Julie Shade, Rheeda Ali and Associates combined machine learning [ML] and personalized computational modeling to predict, prior to pulmonary vein isolation [PVI], which patients are most likely to experience atrial fibrillation [AF] recurrence after PVI. The single center retrospective proof of concept study included 32 patients with documented paroxysmal AF who underwent PVI and had pre-procedural late gadolinium enhanced magnetic resonance imaging [LGE MRI]. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing features were derived from pre-PVI LG MRI images and from results of simulations [SIM] AF. The most predictive features used to input to a quadratic discrimination analysis ML classifier, which was trained, optimized, and evaluated with a 10-fold nested cross validation to predict the probability of AF recurrence post PVI. In the cohort, the ML classifier predicted probability of AF recurrence with an average validation, sensitivity, and specificity of 82% and 89% respectively, and a validation AUC of 0.82. Dissecting the relative contributions of simulations SIM AF and raw images to the predictive capability of the ML classifier, they found that only when features from simulation SIM AF were used to train the ML classifier, its performance retained similar (validation AUC equals 0.81). However, when only features classified from raw images were used for training, the validation AUC significantly decreased (0.47). Paul J. Wang: In our next paper, Sarah Vermij and Associates examined sodium channel NaV 1.5 localization and function mutations in the gene and coding the sodium channel NaV 1.5 caused various cardiac arrhythmias. The authors use novel single-molecule localization [S-M-L-M] and computational modeling to define nanoscale features of NaV 1.5 localization and distribution at the lateral membrane [L-M], the LM groove, and T-tubules in cardiomyocytes from wild-type (N=3), dystrophin-deficient (mdx; N=3) mice, and mice expressing C-terminally truncated NaV 1.5 (ΔSIV; N=3). The authors assessed T-tubules sodium current by recording whole-cell sodium currents in control (N=5) in detubulated (N=5) wild-type cardiomyocytes. The authors found that NaV 1.5 organizes as distinct clusters in the groove and T-tubules which density, distribution, and organization partially depend on SIV and dystrophin. They found that overall reduction in NaV 1.5 expression expressed in mdx and ΔSIV cells result in a non-uniform distribution with NaV 1.5 being specifically reduced at the groove ΔSIV and increased in T-tubules of mdx cardiomyocytes. A T-tubules sodium current could, however, not be demonstrated. The authors concluded that NaV 1.5 mutations may site-specifically affect NaV 1.5 localization and distribution at the lateral membrane and T-tubules, depending on site-specific interacting proteins. Paul J. Wang: In our next paper, Sharan Sharma, Mohit Turagam, and associates studied strategies to improve patient comfort related to pericardial access. They conducted a multi-centered retrospective study, including 104 patients who underwent epicardial ventricular tachycardia [VT] ablation and Lariat left atrial appendage occlusion. They compared 53 patients who received post-procedural intrapericardial liposomal bupivacaine (LB)+oral colchicine (LB group) and 51 patients who received colchicine alone (non-LB group). Lyposomal bupivacaine was associated with significant lowering of median pain scale at 6 hours (1.0 versus 8.0, P

Paul J. Wang: Welcome to the monthly podcast! On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief. With some of the key highlights from this month's issue. Paul J. Wang: In our first paper, Demilade Adedinsewo and associates assess the accuracy of an artificial intelligence-enabled electrocardiogram [AI-ECG] to identify patients presenting with dyspnea who have left ventricular LV systolic function (defined as LV ejection fraction ≤35%) in the emergency department [ED]. Patients were included if they had at least one standard 12-lead electrocardiogram [ECG] acquired on the date of the ED visit and an echocardiogram performed within 30 days of presentation. Patients with prior LV systolic dysfunction were excluded. A total of 1,606 patients were included. Meantime from ECG echocardiogram was one day. The AI-ECG algorithm identified LV systolic dysfunction with an area under the curve [AUC] of 0.89 and accuracy of 85.9%. Sensitivity was 74%, specificity 87%, negative predictive value 97%, and positive predictive value 40%. To identify an ejection fraction less than 50%, the AUC was 0.85, sensitivity 86%, sensitivity 63%, and specificity 91%. NT-proBNP alone with a cutoff greater than 800 identified LV systolic function with an AUC of 0.80 by comparison. Paul J. Wang: In our next paper, Mahmood Alhusseini and associates hypothesize that convolutional neural networks [CNN] may enable objective analysis of intracardiac activation in atrial fibrillation [AF]. They perform panoramic recording of bi-atrial electrical signals in AF and use the Hilbert-transform to produce 175,000 image grids in 35 patients labeled for a rotational activation by experts who showed consistency, but with variability (kappa [κ]=0.79). In each patient, ablation terminated atrial fibrillation. A CNN was developed and trained on 100,000 AF image grids validated on 25,000 grids, and then tested on a separate 50,000 grids. They found in a separate test cohort of 50,000 grids, CNN reproducibly classified AF image grids into those with or without rotational sites with 95.0% accuracy. This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, they applied gradient weighted class activation mapping, which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). The authors concluded that convolutional neural networks improve the classification of intercardiac AF maps compared to other analyses and agreed with expert evaluation. Paul J. Wang: In our next paper, Kenji Okubo and associates examined whether late potential LP, abolition and ventricular tachycardia [VT] non-inclusive ability predicted long-term outcomes in patients with non-ischemic cardiomyopathy [NICM] undergoing VT ablation. The total 403 patients with NICM (523 procedures) who underwent VT ablation from 2010 to 2016 were included. The underlying structural disease consists of dilated cardiomyopathy (DCM, 49%), arrhythmogenic right ventricular cardiomyopathy (ARVD 17%), postmyocarditis (14%), valvular heart disease (8%), congenital heart disease (2%), hypertrophic cardiomyopathy (2%), and others (5%). Epicardial access was performed in 57% of patients. At baseline, the LPs were present in 60% of patients, and a VT was either inducible or sustained/incessant in 85% of the cases. At the end of the procedure LP abolition was achieved in 79% of cases in VT noninducability in 80%. After a multivariate analysis, the combination of LP abolition and VT noninducibility was independently associated with free survival from VT (hazard ratio, 0.45, p = 0.0002) and cardiac death (hazard ratio 0.38, P = 0.005). The benefit of LP abolition of preventing the VT recurrence in ARVD and postmyocarditis appeared superior to that observed for DCM. Paul J. Wang: In our next paper, Domenico Corradi, Jeffrey Saffitz and associates hypothesize that structural molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict postoperative atrial fibrillation [POAF] may identify new molecular pathways and targets for prevention of this common morbid complication. Right atrial appendage [RAA] samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial. 35.2% of patients experienced POAF compared to the non-POAF group. They were significantly older and more likely to have chronic obstructive pulmonary disease or heart failure. They had a higher Euro score and more often underwent valve surgery. No differences in atrial size were observed between POAF and non-POAF patients. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen storage, or connection 43 distribution at the time of surgery, was not significantly associated with the incidents of POAF. None of these histopathological abnormalities were correlated with level of NT pro-BNP, hs-cTnT, CRP, or oxidative stress biomarkers. The authors concluded that in sinus rhythm patients undergoing cardiac surgery, histopathological changes in RAA do not predict POAF. They did not also correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Paul J. Wang: In our next paper, Mark McCauley, Liang Hong, Arvind Sridhar, and associates hypothesize that obesity decreases sodium channel NAF 1.5 expression via enhanced oxidative stress, thus reducing the sodium current and enhancing susceptibility to atrial fibrillation [AF]. They studied a diet induced obese [DIO] mouse model. Pacing induced AF in 100% of DIO mice versus 25% in controls (P 20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia during measurements. LVA ablation was performed in the LA-LVA patients during the follow-up period of a mean of 62 weeks, the EP test-guided group had a significantly lower recurrence rate (19%,11/57 versus 41%, 22/54, P=0.012) and a higher Kaplan-Meier AF/AT-free survival curve compared with controls (P=0.01). No significant differences in the recurrence, and AF/AT-free survival curves between PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analysis identified EP test-guided ablation as a factor, reducing recurrence rates. The recurrence rates in LA-LVA ablation group and EP test-guided group were similar. Paul J. Wang: In our next study, Jinxuan Lin and associates assess whether simultaneous pacing of the left and right bundle branch areas may achieve more synchronous ventricular activation than just bundle pacing alone. In symptomatic bradycardia patients, the distal electrode of the bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing [BBBP] was achieved by stimulating the cathode and anode in various configurations. BBBP was successfully performed in 22 out of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3 vs 118.4 ms, P < 0.001). LBBP resulted in paced RBBB configuration with a DRVAT of 115 ms and interventricular conduction delay of 34.0 ms. BBBP fully resolved the RBBB morphology in 18 patients. In the remaining 4 patients, RBBP pacing partially corrected the right bundle branch block. Paul J. Wang: In our next paper, Ramanathan Parameswaran, Jonathan Kalman, Geoffrey Lee and associates recorded 2-minute long segments of simultaneous inter-operative mapping of endo- and epicardial lateral right atrial [RA] wall in patients with persistent atrial fibrillation [AF] using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms [EGMS] of continuous 2-minute AF recordings and electrodes locations were exported for phase analysis. They defined endocardial-epicardial dissociation [EED] as phase differences of ≥20 ms between paired endo- and epi electrodes. Wavefronts [WF] were classified as single rotations, that is single wavefront, focal waves, or disorganized activity as per standard criteria. Endo-Epi wave fronts were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with directional changes occupying at least 70% of the sample area. 14 patients with persistent AF underwent cardiac surgery are included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (endo 41.3%, epi 46.8%, P = 0.0194) and single wave (endo 31.3 versus epi 28.1, P = 0.129) were the dominant patterns. Transient rotations (endo 22%, epi 19.2%, P = 0.169, mean duration 590 ms) and non-sustained focal waves (endo 1.2% and epi 1.6%, P = 0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P < 0.0001). The authors concluded that simultaneous endo-epi phase mapping of prolonged human persistent AF recordings showed significant EED marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insights into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Paul J. Wang: In our next paper, Andrew Beaser and associates hypothesize that intravascular ultrasound [IVUS] could accurately visualize and quantify intravascular lead adherence and degree of intravascular lead adherence correlates with transvenous lead extraction difficulty. Serial imaging of leads occurred prior to transvenous lead extraction using IVUS. Intravascular lead adherence areas were classified as high or low grade. Degree of extraction difficulty was assessed using 2 metrics and correlated with intravascular lead adherence grade. Lead extraction difficulty was calculated for each patient and compared to IVUS findings. 158 vascular segments in 60 patients were analyzed: 141 (89%) low grade versus 17 (11%) high grade. Median extraction time (low = 0 versus high grade 97 seconds, P < 0.001) and median laser pulsations delivered (low = zero versus high grade 5,852, P < 0.001) were significantly higher in the high-grade segments. Most patients with low lead extraction difficulty score had low intravascular lead adherence grades. 86% of patients with high lead extraction difficulty score had low IVUS grade, and the degree of transvenous lead extraction difficulty was similar to patients with low IVUS grades and lead extraction difficulty scores. Paul J. Wang: In our next paper, András Bratincsák, and associates sought to create the foundation of normative ECG standards in the young using Z-scores. 102 ECG variables were collected from a retrospective cohort of 27,085 study subjects with no known heart conditions, age zero to 39 years. The cohort was divided into 16 age groups by gender. Median interquartile range and range were calculated for each variable adjusted to body surface area. Normative standards were developed for all 102 ECG variables, including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between negative 2.5 and 2.5 were calculated to establish the upper and lower limits of normal. Historical ECG interpretive concepts were reassessed and new concepts observed. The author summarized that electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Paul J. Wang: In our next paper, Jungmin Hwang and associates hypothesize that suppressing the late sodium current may counterbalance the reduced repolarization reserve in long QT syndrome [LQTS] and prevent early depolarization [EAD] and polymorphic ventricular tachycardia [PVT]. They tested the effects of selective late sodium channel blocker GS967 on polymorphic ventricular tachycardia [PVT] induction in a transgenic rabbit model of type two using intact heart optical mapping, cellular electrophysiology, and confocal calcium imaging and computer modeling. They found that GS967 reduced ventricular fibrillation [VF] induction under a rapid pacing protocol (7 out of 14 hearts in control versus 1 out of 14 at 100 nanomolar) without altering action potential duration [APD] or restitution and dispersion. GS967 suppressed PVT incidents by reducing calcium mediated EADs and focal activity during isoproterenol perfusion (at 30 nanomolar, 7 out of 12 and a 100 nanomolar, 8 out of 12 without EADs and PVTs). Confocal calcium imaging of LQT myocytes revealed GS967 shortened calcium transient duration by accelerating sodium calcium exchanger mediated calcium efflux from cytosol, thereby reducing EADs. Computer modeling revealed the inward late sodium current potentiates EADs in the LQT setting through providing additional depolarizing currents through action potential plateau phase, and increasing intracellular sodium that decreases the depolarizing sodium calcium exchanger, thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier current, IKS. Suggesting important roles in the late sodium current in regulating intracellular sodium. Thus, the authors concluded that selective late sodium channel blockade by GS967 prevents EADs and abolishes PVT in LQT rabbits by counterbalancing the reduced repolarization reserve and normalizing intracellular sodium. Paul J. Wang: In our next paper, Pietro Lazzerini, Mohamed Boutjdir and associates, hypothesize that systemic inflammation per se can significantly prolong QTc during infection via cytokine-mediated changes in potassium channel expression. They found in patients with acute infections, regardless of concomitant QT-prolonging anti-microbial therapy, QTc was significantly prolonged but rapidly normalized in parallel to C-reactive protein [CRP] and cytokine level reduction. Consistently, in Torsades de Pointes cohort, concomitant acute infections were prevalent 30% despite only a minority (25%) of these cases were treated with QT-prolonging anti-microbials. KCN J2, potassium channel expression in peripheral blood mononuclear cells was strongly correlated to that in ventricles, inversely associated to CRP and interleukin one changes in acute infection patients. The authors concluded that acute infection, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless of concomitant antimicrobial therapy. Paul J. Wang: In a research letter, Christophe Beyls and associates examined the risk of bradycardia and critically ill COVID-19 patients treated with Lopinavir [LPV], a protease inhibitor of HIV-1, and Ritonavir [RTV], another protease inhibitor that strongly inhibits hepatic cytochrome P 450 [CYP3A4] activity in order to increase the Lopinavir plasma concentration. During the first month of the outbreak, patients admitted to the ICU with positive PCR for COVID-19 received LPV (200 mg)/RVT (50 mg) twice daily for 10 days. Bradycardia was defined as heart rate below 60 for a period of more than 24 hours. All patients were monitored 24 hours a day for all hemodynamic parameters, including heart rate with a five-lead ECG. Monitors were linked to a computerized system allowing to extract hemodynamic data. LPV/RTV plasma concentration was monitored using analytic method, combining high propensity performance, liquid chromatography and tandem mass spectrometry at 72 hours and every 72 hours. They prospectively included 41 COVID-19 patients who received LPV/RTV treatment. Nine or 22% patients experienced bradycardia. No patients had a pre-existing nodal pathology on the ECG on admission. Among the 9 patients with bradycardia, 8 or 88% were sinus bradycardia and one (12%) third-degree AV block. Causality may be considered as bradycardia occurred at least 48 hours after LPV/RTV initiation, bradycardia resolved after discontinuation or dose reduction and no alternative cause was found. Patients who presented with bradycardia were older, had a higher RTV plasma concentration and a lower lymphocyte count. In our study, no correlation was found between RTV plasma concentration, LPV plasma concentration, and mean heart rate at day three. No patient had bradycardia in the first 48 hours after LPV/RTV administration. For patients with LPV RTV plasma level overdose, the dose of LPV RTV was divided by two until the next dose. For the patient with third degree AV block LPV/RTV was stopped. None of the patients had any known cytochrome CYP3A4-inhibiting drugs. The authors concluded that the results suggest that RTV plasma overdose in elderly critical ill patients may increase the risk of bradycardia. Paul J. Wang: In a research letter, Emily Zeitler and associates surveyed cardiac implantable device [CID] patients. A total of 109 patients were approached to participate, nine declined. Most respondents were white (79%), male (60%) with a mean age of 73 years. The median number of correct responses to the 11 factual questions was six. Respondents held some common misconceptions. For example, 25% of respondents believe that FDA determines the cost of the device. Trust in the FDA was high; 67% of respondents agreed "I trust the FDA". Respondents mostly agreed "the FDA would not approve my device unless it was a hundred percent safe". Only 6% of respondents agreed, "we would be better off if there was no FDA," and a similarly small fraction disagreed with "when it comes to medical devices, the U.S. does the best job in the world at keeping people safe". Most respondents, 69% demonstrated fear of device recalls by agreeing with "if there was a recall of all are part of my device, I think I would be worried or scared." On average, respondents were comfortable sacrificing some privacy for device surveillance, 75% agreed with "once the device has been approved, the FDA should continue to monitor for signs that there are problems with the device even if it means that private health information about me is collected". Respondents seemed to believe that the FDA was risk averse; 56% believed that the FDA does not approve devices unless they're a hundred percent safe. This is in contrast to trends shifting the demonstration of safety to post-approval settings and expanding acceptable forms of data for regulatory approval. Paul J. Wang: In a research letter, Laura Rottner, Christoph Sinning and associates examined novel high resolution imaging system based on a wide band dielectric technology, and reports the first clinical experience of feasibility and reliability of cryoballoon [CB] occlusion tool as compared to fluoroscopic and 3D transesophogeal [TEE] assessment during pulmonary vein isolation [PVI]. In consecutive patients with symptomatic atrial fibrillation [AF], cryoballoon-based ablation was performed with a novel 3D wide-band dielectric imaging system. Pulmonary vein [PV] occlusion was assessed with fluoroscopy in 3D-TEE and concomitantly correlated with the novel CB occlusion tool. The endpoint was defined as persistent PV isolation verified by spiral mapping catheter recordings 30 minutes after the last CB application. A total of 36 (90%) of PVs in 10 patients with paroxysmal (40%) and persistent (60%) were analyzed. In all patients, a normal PV anatomy with four separate PVs was documented. Visualization via 3D-TEE was feasible in 80% septal PVs and 100% of lateral PVs. In 67% of PVs, total PV occlusion was confirmed by all 3 imaging modalities. In 17% of PVs, incomplete PV occlusion was initially demonstrated by TEE and 3D dielectric imaging, whereas fluoroscopy suggested complete occlusion in initial analysis. After repositioning of the CB at 3 PVs, complete PV occlusion was verified by all three modalities. In 3 out of 36 (8%), no occlusion was initially seen by any imaging modality, for which the CB was repositioned resulting in total PV occlusion as confirmed by all three modalities. Two out of 36 PVs (6%) were confirmed to be occluded via fluoroscopy in 3D-TEE, but not by the CB occlusion tool. There was only one out of 36 PVs (3%), which were confirmed to be included by the CB tool and 3D-TEE, but not by fluoroscopy. A negative and positive predictive value of 1.0 and 0.6 was seen when comparing PV occlusion by the novel occlusion tool compared to PV collusion, verified by fluoroscopy and 3D-TEE. Paul J. Wang: In a special report, Jun Hirokami, and associates aim to clarify the spatial correlations between fractionated potential detected by Lumipoint with non-PV trigger. They enrolled 30 symptomatic atrial fibrillation [AF] patients who underwent non pulmonary vein [PV] foci ablation. 4 patients underwent the first procedure, 17 underwent second procedure and eight underwent third procedure, and one underwent a fourth procedure. They highlighted the fractionated signal area in atrial muscle [FAAM] during sinus rhythm and atrial pacing, thereby producing a digital FAAM map. They retrospectively applied Lumipoint to 30 patients in order to clarify the relationship between FAAM and non-pulmonary vein [PV] foci. Non-PV foci were successfully identified in all patients. They identified four patients with multiple non-PV foci. Of these four patients, one had non-PV foci at the superior vena cava and left arterial anterior wall. One had non-PV foci at the SVC and LA bottom wall. And two had non-PV foci at the SVC and interatrial septum. They only analyze 30 non-PV foci unrelated to SVC because the SVC isolation was routinely performed for non-PVC foci at the SVC. In order to analyze the correlation between FAAM and location of non-PV triggers, they determined the cutoff points of peaks slider, which non-PV triggers were completely located within the FAAM in. The accuracy of predicting location of the non-PV triggers was summarized using area under the receiver operating curve, a UROC curve. The optimal cutoff point of peak sliders to predict the location of non-PV was determined by the Youden Index. The Youden Index established the optimal cutoff point of the maximum peaks slider was 7; sensitivity was 0.906 and specificity 0.770. The peaks slider 7 was the most accurate predictor fractionated signals location area to the location of non-PV triggers. (area under the curve 0.902). The mean area of peaks slider 7 was six centimeters squared or 4.3% of the atrium. The authors concluded that the proof-of-concept observational study demonstrated that novel visualization tool of FAAM map successfully identified non-PV triggers that did not induce atrial fibrillation and/or non-PV foci, which potentially serve as substrates for AF maintenance. Paul J. Wang: In a special report, Leslie Saxon and associates update their prior publication providing further detail on mitigation adoption rates for the entirety of the U.S. patient population with implanted cardiac rhythm management devices falling under FDA cyber security advisories from any device manufacturer. They also provided limited data on known cybersecurity mitigation adoption outside the U.S. They report a unique complication resulting for introducing firmware to already implanted devices. Discuss how evolving FDA policies towards firmware mitigation adoption may increasingly determine how and when updates occur. They found that patients under 50 years of age and those over 80 years were less likely to receive the software upgrades, and male versus females had greater rates of upgrades. The upgrade rates varied according to U.S. Region and date of implant. Resynchronization devices were less likely to receive the upgrade, as were pacemaker dependent patient. Those ICD patients initially falling under the battery advisers were upgraded more frequently. The number of advisory patients followed in clinic was a significant predictor for firmware upgrade adoption, particularly for pacemakers that were often upgraded in smaller size clinics. Overall, only 24% of devices for all groups, and 22% of devices not impacted by the battery advisory were upgraded. For Abbott devices, the home communicator cyber security vulnerabilities were mitigated with an automatic software patch that was updated using the Merlin network, and adoption rates were nearly a hundred percent. For the entire patient cohort with impacted pacemaker and ICDs, U.S. and global adoption rates remain low at 24 to 35% with a low rate of complications. Most reported complications for pacemakers and ICD were symptoms (transient palpitations, dizziness, or syncope) that resulted from the temporary change in mode to VVI or transient loss of programmer telemetry while performing the upgrade (pacemaker 0.05%; ICD 0.01%). Globally, a total of 9 pacemakers and 8 ICDs required replacement, as a result of performing the firmware upgrade due to irreversible reversion to a backup pacing mode and loss of defibrillation therapy (ICDs). Analysis of the returned ICD pulse generaotrs found at 7 cases, the cause related to a capacitor bond failure that was exposed only when extended telemetry as required by the upgrade. The failure mechanism was an isolated component failure in the remaining ICD. The programmer based test has recently been FDA approved and can be performed prior to firmware upgrade to identify ICD patients at risk for capacitor bond failure. A total of 256 ICDs were susceptible to loss of RF telemetry after receiving a firmware update, and this has since been mitigated with a software patch. For Medtronic programmers, the initial mitigation responses of cybersecurity advisory was to take the programmers off the network. The network connection was enhanced with one or more security protections provided to the programmers using a flash drive, so the programmers can now be secured from potential cyber intrusion when connected to the network. Medtronic ICDs are currently being upgraded. The upgrade is being provided to impacted patients automatically when the device is interrogated with the programmer during follow-up. Metronic is introducing upgrades in phased approach with all expected to be completed by the beginning of 2021. There are 9% or 55,000 ICDs under this advisory that cannot receive the update due to design or safety constraints. Since the 2017 Abbott advisories identify cybersecurity vulnerabilities in pacemakers and ICDs with the potential for exploits have been increased, including 2 additional FDA advisories issued for another manufacturer. Medtronic's connected communication product and implantable defibrillators in the past 12 months. The authors comment that a recent report and a smaller number of Abbott impacted pacemaker and ICD patients from Canada reported marked differences in mitigation adoption rates between pacemakers and ICDs. This was due to an increase incremental clinical familiarity and comfort with performing the updates as experience and education surrounding these issues evolve. The authors indicate that automating cybersecurity updates without process in place for determining safety, for alerting patients or clinicians that have been delivered, may also be associated with yet unknown risks. Newer generation devices and communication protocols may render cyber security, advisories less frequent as cybersecurity integration is considered an essential aspect of device design. Paul J. Wang: In a review article, Albert Feeny and associates discuss the use of artificial intelligence [AI] and machine learning [ML] in medicine, which are currently areas of intense exploration showing potential to automate human tasks or even perform tasks beyond human capabilities. The first objective of this review is to provide the novice reader with a literacy of AI/ML methods, and to provide a foundation of how one may conduct an ML study. The review provides a technical overview of some of the most commonly used terms, challenges in AI/ML studies with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from the recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology with emphasis on disease detection and diagnosis, prediction, and patient outcomes and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate variation, adoption, and deployment of AI technologies and practice. Paul J. Wang: That's it for this month! We hope that you will find the journal to be the go-to place for everyone interested in the field! See you next time! This program is copyright American Heart Association 2020. Thank you.  

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue.   In our first paper, Vivek Reddy and associates studied a novel, 7.5, French lattice tip catheter with the compressible 9 mm nitinol tip that is able to deliver either focal radio frequency ablation [RFA] or pulsed field ablation [PFA], 2 to 5 second lesions. In a 3 center, single-arm, first in human trial, the catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point by point, pulmonary vein [PV] encirclement was performed using biphasic pulsed field ablation, posteriorly, and either temperature controlled irrigated RFA or pulse field ablation, anteriorly (RF/PF or PF/PF) respectively. Linear lesions were created with either PFA or RFA. The 76 patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation [AF] patients undergoing either RF/PF [pulse field ablation] 40 patients or PF/PF ablation in 36 patients, pulmonary vein isolation therapy duration was 22.6 minutes per patient with a mean of 50.1 RF/PF ablation lesions per patient. Linear lesions included 14 mitral, 34 left atrial roof and 44 cavo-tricuspid isthmus lines with therapy duration times of 5.1, 1.8 and 2.4 min/patient respectively. All lesion sets were acutely successful using 4.7 minutes of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in two of the 36 RF/PF and zero of the 24 PF/PF patients. Post-procedure brain MRI revealed DWI positive flair, negative and DWI positive flare positive asymptomatic lesions in 5 and 3 of the 51 patients respectively.   In our next paper, Moussa Saleh and associates examined whether chloroquine, hydroxychloroquine plus or minus azithromycin lead to a prolongation of the QT interval, possibly increasing the risk of torsades de pointes and sudden death in a hospitalized population of patients with COVID-19. 201 patients were treated for COVID-19 with chloroquine/hydroxychloroquine. 10 patients or 5% received chloroquine, and 191 or 95% received hydroxychloroquine and 119 or 59% also received azithromycin. The primary outcome of Torsades de pointes was not observed in the entire population. Baseline QTC interval did not differ between patients treated with chloroquine or hydroxychloroquine monotherapy versus those treated with combination group chloroquine/hydroxychloroquine and azithromycin (440 ms versus 439.9 ms). The maximum QT during treatment was significantly longer in the combination versus the monotherapy group, 470 ms versus 453 ms (P = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTC prolongation. No arrhythmic deaths were reported.   In our next paper, Mikko Tulppo and associates examine whether the association between leisure time physical activity and the risk of sudden death and non-sudden cardiac death in coronary artery disease patients. 1,946 patients with angiographically verified coronary artery disease were classified into four groups: inactive, irregularly active, active exercise regularly two to three times per week, and highly active, exercise four times or more weekly. During follow-up, median 6.3 years, 52 sudden cardiac death and 49 non-sudden cardiac deaths occurred. Inactive patients had increased risk for sudden cardiac death compared to active patients, hazard ratio 2.45. Leisure time was not associated with sudden cardiac death in patients with Canadian cardiovascular class one, 18 events in 1,107 patients. Among patients with Canadian cardiovascular society, class two or higher, 34 events in 839 patients. An increased risk for sudden cardiac death encountered in highly active patients, hazard ratio 7.46 (P < 0.001). In inactive patients hazard ratio 3.64 as compared to active patients. A linear association was observed between leisure time, physical activity and non-sudden cardiac death. Those with high leisure time physical activity had the lowest risk for non sudden cardiac death.   In our next paper, Jacob Koruth and associates examined the preclinical feasibility and safety of a 9mm lattice tip catheter with focal biphasic pulse field [PF] based thoracic vein isolation and linear ablation combined focal biphasic pulse field and radio-frequency [RF] focal ablation and vocal biphasic pulse field delivered directly on top of the esophagus. They treated two cohorts of six swine with pulse fields at low dose and high dose followed for four weeks and two weeks, respectively to isolate 25 thoracic veins and to create five right atrial low dose PF, six mitral high dose PF, and six roof lines with combined RF and high dose PF. Baseline and follow-up voltage mapping, venus potentials, ostial diameters and phrenic nerve viability were assessed. High dose PF in RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviate esophagus. 100% of thoracic veins, 25 out of 25, were successfully isolated with 12.4 applications per vein with a mean pulse field times of less than 90 seconds per vein. Durable isolation improved from 61.5% in the low dose pulse field to 100% with a high dose pulse field (P = 0.04). And all linear lesions were successfully completed without incurring venous stenosis or phrenic injury. High dose pulse field sections had higher trans mortality rates than low dose pulse field (98.3% versus 88.1%, P = 0.03). Despite greater thickness, 2.5 versus 1.3 mm, pulse field lesions demonstrated homogeneous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, combined RF plus high dose PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation related esophageal and necrosis inflammation and fibrosis were seen in all RF sections as compared to no PF sections.   In our next paper, Hagai Yavin and associates investigated the effects of a novel, lattice tip catheter designed for focal radiofrequency ablation [RFA] or pulse field ablation in 25 swine. In 14 animals, they examined in step one (n = 14) the feasibility to create atrial line of block and described as acute effects on the phrenic nerve and esophagus. In step two (n = 7), they examined the subacute effects of pulse field ablation on block durability, phrenic nerve, and esophagus 2 or more weeks. In 4 animals in step three, they compare the effects of pulse field ablation and RFA on the esophagus using a mechanical deviation model, approximating the esophagus through the right atrium in 4 and direct ablation honest lumen in 4. The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n = 10). Histological analysis were performed. Pulse field ablation produced acute block in 100% of lines achieved with 2.1 applications per centimeter line. Histological analysis following a mean of 35 days showed 100% transmurality (thickness range 0.4 to 3.4 mm) with a lesion width of 19.4 mm. Pulse field ablation selectively affected cardiomyocytes, but spared blood vessels and nervous tissue. Pulse field ablation applied from the posterior atrium to the approximated esophagus produced transmural lesions without esophageal injury. Pulse field ablation applied within the esophageal lumen produced mild edema compared to radiofrequency ablation (13 applications) which produced epithelial ulcerations. Pulse field ablation resulted in no or transient stunning of the phrenic nerve, less than 5 minutes without histological changes while radiofrequency ablation produced paralysis.   In our next paper, Elad Anter and associates investigated the optimal methods to identify arrhythmogenic substrate of scar related VT. They examine how often sites of activation slowing during sinus rhythm co localize with ventricular tachycardia VT circuit. In a multicenter study in patients with infarct-related VT, the left ventricle was mapped during activation from three directions, sinus rhythm, or atrial pacing, right ventricular and left ventricular LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation defined as a sum of all regions with activation time of 40 ms or greater per 10 mm. Hemodynamically tolerated ventricular tachycardias or VT were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death. In 85 patients, the left ventricle was mapped during activation from 2.4 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spacial overlap of activation slowing between sinus rhythm and right ventricular RV pacing was 84.2%, between sinus rhythm and LV pacing was 61.4%, and between right ventricular and left ventricular pacing, 71.3% (P < 0.05) between all comparisons. Mapping during sinus rhythm identified only 66.2% of the entire area of activation slowing and 58% of critical isthmus sites. Activation from other directions, right ventricular or left ventricular stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point incurred in 14 out of 85 or 16.5% of patients. The authors concluded that the spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct.   In our next paper, Georg Gussak and associates identified a novel form of abnormal calcium wave activity in normal and failing dog atrial myocytes, which occurs during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial myocytes, depending on the holding potential. This current could be responsible for action potential (AP) activation during repolarization induced by triggered waves. Modeling studies demonstrate the characteristic properties of triggered calcium waves are potentially arrhythmogenic by promoting both conduction block and reentry arising from the repolarization induced by triggered calcium waves. The authors concluded that triggered calcium waves activate inward sodium calcium exchange and dramatically reduce atrial maximum diastolic potential and prolonged action potential duration establishing the substrate for reentry that could contribute to initiation and maintenance of atrial arrhythmias.   In our next paper Faisal Merchant and Omid Sayadi and associates evaluate the ability of a real-time, closed loop system to record and analyze repolarization alternans from multiple intracardiac leads and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. They examined the ability of this system to control repolarization alternans and reduce arrhythmia susceptibility, in vivo. R-wave trigger pacing can induce repolarization alternans, the magnitude of which can be modulated by varying the amplitude, pulse width, or size of the pacing vector. Using a swine model (n = 9), the authors demonstrated that to induce 1 microvolt change in the alternans voltage on the body surface, coronary sinus or left ventricle, requires a delivery charge of 0.04, 0.05 and 0.06 microcoulombs, respectively, while to induce one unit change of the case score requires a delivery charge of 0.93, 0.32 and 0.33 microcoulombs, respectively. For all body surface and intracardiac leads a Delta alternans voltage and Delta K score between baseline and R-wave triggered pace peaks increases consistently with an increase in the pacing pulse amplitude, pulse width and vector spacing. Additionally, the author showed that the proposed method can be used to suppress spontaneously occurring alternans (n = 7), in the presence of myocardial ischemia. Suppression of repolarization alternans by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by lower S rank score during program ventricular stimulation compared to baseline prior to ischemia.   In a perspective outlining the cardiovascular effects of chloroquine and hydroxychloroquine, Ohad Oren and associates describe their belief that the use of chloroquine and hydroxychloroquine in COVID-19 should be limited to randomized, controlled trials. For critically ill patients, unable to enroll in a trial, selective in-hospital use could be considered with careful clinical monitoring in keeping with the FDA's emergency use authorization. The authors suggested that studies evaluating chloroquine and hydroxychloroquine should systematically collect baseline demographic data, results from electrocardiographic and echocardiographic monitoring prior to and during treatment and rates of adverse cardiovascular events in both the near and long-term.   In a research letter, Federico Migliore and Alessandro Zorzi and associates found a 28% decrease in the number of urgent pacemaker implantations during the six weeks after the first COVID-19 case, from 122 to 88 (P = 0.02), compared to the six weeks before the first COVID-19 case. The proportion of female patients requiring urgent pacemaker implantation after the COVID-19 outbreak decreased from six out of 122 (49%) to 30 out of 88 (34%) (P = 0.03).   In a special report Stephanie Kochav and associates described 4 cases of cardiac arrhythmias in COVID-19, including AV block, atrial fibrillation, polymorphic ventricular tachycardia, and pulseless electrical activity arrest.   In a year in review, Suraj Kapa and associates discuss a number of the many advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies in the past year. Data suggests that secretoneurin may be a marker for patients at risk of ventricular arrhythmias, while natriuretic peptide receptor C may have a role in atrial fibrosis. In atrial specific 2-pore potassium channel TASK-1 may be a therapeutic target for atrial fibrillation. Sensory neurons may play a key role in sleep apnea related to atrial fibrillation. Bariatric surgery is associated with improved atrial fibrillation outcome. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We've seen new tools for collection of patient centered outcomes following catheter ablation. There's been significant advances in the ability to identify ventricular tachycardia termination sites through high density mapping of deceleration zones. We've learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non ischemic cardiomyopathy patients. We've seen further insights in the role of his bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we have new tools to predict arrhythmic event rates in gene carriers. And finally, we've seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.   That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.  

Paul J. Wang: Welcome to the monthly podcast On the Beat for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor In Chief, with some of the key highlights from this month's issue.   Elizabeth Wang and Associates examined the relationship between acute precipitants of atrial fibrillation and long-term recurrence of atrial fibrillation, AF, from a multi-institutional, longitudinal electronic medical record database. Among 10,723 patients with newly diagnosed Afib, age 67.9 years, 41% women, the authors found that 19% had an acute AF precipitant, the most common of which were cardiac surgery in 22%, pneumonia in 20% and non-cardiothoracic surgery in 15%. The cumulative incidence of AF recurrence at five years was 41% among individuals with a precipitant, compared to 52% in those without a precipitant. Adjusted hazard ratio 0.75 P < 0.001. The lowest risk of recurrence among those with precipitants with postoperative atrial fibrillation, five-year incidence 32% in cardiac surgery and 39% in non-cardiothoracic surgery. Regardless of the initial precipitant, recurrent atrial fibrillation was associated with an increased adjusted risk of heart failure, hazard ratio of 2.74 P < 0.001, Stroke, hazard ratio 1.57 P < 0.001 and mortality, hazard ratio 2.96 P < 0.001. Thus, the authors found that atrial fibrillation after acute precipitant frequently recurs and the recurrence is associated with substantial long-term morbidity and mortality.   In the next paper, Jacob Koruth and associates examine the effect of pulse field ablation on the esophagus in a novel in-vivo porcine esophageal injury model. The authors studied 10 animals under general anesthesia while the lower esophagus was deflected towards the inferior vena cava using an esophageal deviation balloon and ablation was formed from within the inferior vena cava at areas of esophageal contact. Six animals received eight pulse field ablation applications per site and four animals received six clusters of irrigated radio frequency ablation applications at 30 Watts for 30 seconds. All animals survived to 25 days, sacrificed, and the esophagus was submitted for a pathological examination including 10 discreet histological sections of the esophagus. The authors found that zero out of six pulse field ablation animals demonstrated esophageal lesions while esophageal injury occurred in all four radio frequency ablation animals, P = 0.005. A mean of 1.5 mucosal lesions per animal, length 21.8 millimeters with 4.9 millimeters were observed, including one esophageal pulmonary fistula, and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by an acute and chronic inflammation and fibrosis. The necrotic radio frequency ablation lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of peri-esophageal nerves, abscess formation and full thickness esophageal wall disruption were seen in the areas of perforation or fistula.   In our next paper, Peter Noseworthy and associates examine whether the ability of deep learning algorithms to detect low left ventricular ejection fraction using the 12 lead electrocardiogram varies by race or ethnicity. The authors used a retrospective cohort analysis and included 97,829 patients with paired electrocardiograms and echocardiograms and used a convolutional neural network to identify patients with a left ventricular ejection fraction less than or equal to 35% from the 12 lead electrocardiogram. The convolutional neural network was previously derived in a homogeneous population, 96.2% non Hispanic white, N = 44,959 which demonstrated consistent performance to detect low left ventricular ejection fraction across a range of racial ethnic subgroups in a separate cohort of 52,870 patients (Non-Hispanic white 44,524 patients with an AUC of 0.93; Asian 557 with an AUC of 0.96; Black/African American N = 651 with an AUC of 0.937; in Hispanic/Latino N = 331 AUC of 0.937; in Native American/Alaskan N = 223 AUC of 0.938). In secondary analysis, a separate neural network was able to discern racial subgroup category, Black/African American AUC 0.84 and white non-Hispanic AUC 0.75 in a five-class classifier. In a network trained only in non-Hispanic whites, from the original derivation cohort, performed similarly well across a range of racial ethnic subgroups in the testing cohort with at least an AUC of 0.93 in all racial ethnic subgroups. The authors concluded that while ECG characteristics vary by race, this did not impact the ability of a convolutional neural network to predict low left ventricular ejection fraction from the ECGs. They recommend reporting of performance against diverse ethnic, racial, age, and gender groups for all new artificial intelligent tools.   In our next paper, Benjamin Shoemaker and associates examine the association between atrial fibrillation or AF genetic susceptibility and recurrence after de novo AF ablation, using a comprehensive polygenic risk score for AF in the 10 centers from the AF genetics consortium. AF genetic susceptibility was measured using a previously described a polygenic risk score, N = 929 snips. The overall arrhythmia recurrence rate between 3 and 12 months was 44% in 3,259 patients. Patients with a higher AF genetic susceptibility were younger and have fewer clinical risk factors for atrial fibrillation. Persistent atrial fibrillation has a ratio of 1.39, left atrial size has a ratio of 1.32, and left ventricular ejection fraction per 10% has a ratio of 0.88, were associated with increased risk of occurrence. In unit varied analysis, the authors found that AF genetic susceptibility had a hazard ratio of 1.08 P = 0.07 and in multivariate analysis hazard ratio 1.06 with a P value 0.13.   In our next paper, Mohit Turagam and associates reported the outcomes of the first inhuman value trial, which uses low intensity collimated ultrasound or LICU guided anatomical mapping in robotic ablation to isolate the pulmonary veins for atrial fibrillation ablation. In 52 paroxysmal atrial fibrillation patients, ultrasound M-mode based left atrial anatomies were successfully created and ablation was performed under robotic control along an operated defined lesion path. The operatives found that acute pulmonary vein isolation was achieved in 98% of pulmonary veins using LICU only in 77% of pulmonary veins and requiring touch-up with a standard radio frequency ablation catheter in 23% of the pulmonary veins. The touch up rate decreased to 5.8% in patients undergoing LICU ablation with an enhanced software. Freedom from atrial relational recurrence was 79.6% at 12 months or 92.3%, 12 out of 13 patients with the enhanced software. Major adverse events occurred in three patients or 5.8%. One had transient diaphragmatic paralysis, one vascular access complication and one had transient ST segment elevation from air-embolism without sequelae.   In our next paper, Miguel Rodrigo and associates mapped electrical patterns of disorganization and reasons of reentrant activity in atrial fibrillation, or AF, from the body surface using electrocardiographic imaging. The author examined the bi-atrial intracardiac electrograms of 47 patients at ablation (30 persistent, 29 males, age 63 years) obtained using 64-pole basket catheters while simultaneously recording 57-lead body surface electrocardiogram. The authors found the body surface mapping showed greater atrial fibrillation organization near intracardiac detected drivers and elsewhere, both in phase singularity density in numbers of drivers, they found that complexity defined as a number of stable AF reentrant sites was concordant between the noninvasive and invasive methods. The subset receiving targeted ablation, AF complexity, showed lower values in those in whom AF terminated than in those in whom AF did not terminate, P < 0.01. The authors concluded that AF complexity, assessed noninvasively, correlates well with organized, disorganized regions detected by intracardiac mapping.   In our next paper, Krystien Lieve and Veronica Dusi and associates examined whether heart rate reduction immediately after exercise is regulated by autonomic reflexes, particularly vagal tone and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia, CPVT. In a retrospective observational study, the authors studied 187 patients mean age 36 years, 68 or 36% symptomatic before diagnosis, pre-exercise stress test heart rate and maximal heart rate were equal amongst symptomatic and asymptomatic patients. Patients that were symptomatic prior to diagnosis had a greater delta HRR one prime after a maximum exercise, 43 versus 25, P < 0.001. Corrected for age, gender, and relatedness, patients in the upper tertile for Delta HRR one prime had an odd ratio of 3.4 of being symptomatic before diagnosis, P < 0.001. In addition, Delta HRR one prime was higher in patients with complex ventricular arrhythmias at exercise stress test, off antiarrhythmic drugs. After diagnosis, patients with a Delta HRR one prime in the upper tertile of its distribution, had significantly more rhythmic events as compared to patients and other tertiles, P=0.045. The authors concluded that CPVT patients with a larger heart rate reduction following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during first exercise stress test off antiarrhythmic drugs.   In our next paper, Balvinder Handa and associates examined whether low spatial resolution, sequentially acquired data can be used to examine the global fibrillation organization, characterizing dominant propagating patterns and identifying rotational drivers. The authors employed ranger causality analysis, an econometric tool for quantifying causal relationships between complex time series, which was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data. Ventricular fibrillation, or VF, optical mapping was performed and Langendorff-perfused Sprague Dawley rat hearts, N = 18. And novel algorithms were developed using Granger causality analysis to quantify causal dependence of neighboring signals and plot Granger causality analysis vectors, quantify global organization using causality pairing index, a measure of neighboring causal signal pairs, and localize rotational drivers by quantifying the circular interdependence of neighboring signals with the circular interdependence value. Granger causality analysis based mapping tools were optimized for low spatial resolution by down sampled optical mapping data validated against high resolution phase mapping analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart LV wedge preparations, N = 12, and adaptive for sequentially acquired intracardiac electric Grande during human persistent atrial relation mapping, N=16. The authors found that global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions in organized VF with high causality pairing index values. Ranger causality analysis vector mapping characterize dominant propagating patterns and localized stable rotational drivers with the circular interdependence value showing a significant difference in driver versus non driver regions, P = 0.0002. These findings were further confirmed in human VF in persistent atrial fibrillation, a positive correlation was found between causality peri-index and presence of stable rotational drivers. 50% of patients had rotational drivers with a low incidence of 0.9 rotational drivers per patient. In a special report, Piotr Futyma and associates report on the use of bipolar radiofrequency ablation of ventricular arrhythmias originating in the vicinity of the His bundle. Bryce Alexander and associates report in a research letter the patient acceptance of cybersecurity upgrade in ICDs.   That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time.   This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.   In our first paper, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy.   They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death.   At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates examine the impact of cardiac implantable electronic device [CIED] infections on mortality, quality of life, healthcare utilization, and cost in the U.S. Healthcare system. They found that the majority CIED infection was associated with increased all-cause mortality, 12-month risk-adjusted hazard ratio 3.41, P < 0.001. An effect that sustained beyond 12 months.   The quality of life was reduced, P = 0.004, and did not normalize for six months. Disruptions in CIED therapy were observed in 36% of infections for a median duration of 184 days. The authors reported that the mean hospital costs were $55,547.   In our next paper, Songwen Chen, Xiaofeng Lu and associates examine the ability to eliminate premature ventricular complexes [PVCs] originating from the proximal left anterior fascicle, safely from the right coronary sinus. The authors mapped the the right coronary sinus and left ventricle in 20 patients with left anterior fascicle PVCs. They found that the earliest activation site with Purkinje potential during both PVC and sinus rhythm was localized at proximal left anterior fascicle in eight patients, the proximal group, or non-proximal left anterior fascicle in 12 groups, the non-proximal group. The Purkinje potentials proceeded PVC-QRS at the earliest activation site in proximal group 32.6 milliseconds was significantly earlier than that in non-proximal group, 28.3 milliseconds P = 0.025. Similar difference in the Purkinje potentials proceeding sinus QRS at the earliest activation site was also observed between proximal and non-proximal group, 35.1 milliseconds versus 25.2 milliseconds, P < 0.001.   In proximal group, the distance between the earliest activation site to the left His-bundle into the right coronary sinus were shorter than that of the non-proximal group 12.3 millimeters versus 19.7, P = 0.002, and 3.9 millimeters versus 15.7 millimeters, P < 0.001, respectively. The authors found no difference in the distance between the right coronary sinus to proximal left anterior fascicle between the two groups. PVCs were successfully eliminated from the right coronary sinus in all proximal group, but at left ventricular earliest activation site for the non-proximal group, the radiofrequency application time, ablation time and procedure time of non-proximal group were longer than that proximal group.   Electrocardiographic analysis showed that when compared to non-proximal group, the PVCs proximal group had a narrower QRS duration, smaller S wave in leads one, V five,and V six; lower R waves in leads one, aVL, aVR, V one, V two, and V four and smaller q wave in leads three and aVF. The QRS duration difference [PVC-QRS and sinus rhythm QRS] < 15 milliseconds predicted the proximal left anterior fascicle origin with high sensitivity and specificity.   In our next paper, Benjamin Steinberg and associates examined the factors that are associated with large improvements in health-related quality of life in patients with atrial fibrillation. The authors assessed factors associated with a one-year increase in quality of life, measured by AFEQT of one standard deviation that is greater and equal to 18 points, three times clinically important difference among patients in the ORBIT-AF one registry. They found that 28% of patients had such a health-related quality improvement compared with patients not showing large health-related quality of life improvement. They were similar age, (median 73 versus 74 years of age), equally likely to be female, (44% versus 48%), but more likely to have newly diagnosed atrial fibrillation [AF] at baseline (18% versus 8%, P = 0.0004) prior antiarrhythmic drug use (52% versus 40%, P = 0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P = 0.045), and more likely to undergo AF related procedures during follow-up (AF ablation 6.6% versus 2.0%, cardioversion 12.2% versus 5.9%). In multivariate analysis, a history of alcohol abuse has a ratio 2.4 and increased baseline diastolic blood pressure has a ratio 1.23 per 10 point increase and greater than 65 millimeters of mercury were associated with large improvements in health-related quality of life at one year. Whereas patients with prior stroke, chronic obstructive pulmonary disease and peripheral artery disease were less likely to improve.   In our next paper, Eiichi Watanabe and associates studied safety and resource consumption of exclusive remote follow-up in pacemaker patients for two years. Consecutive pacemaker patients committed to remote pacemaker management were randomized to either remote follow-up or conventional in-office follow-up at twice yearly intervals.   Remote follow-up patients were only seen if indicated by remote monitoring, all returned to hospital after two years. In 1,274 randomized patients (50.4% female, age 77 years), 558 remote follow-up or 550 conventional in office follow-up patients reached either the primary end point or 24 months follow-up. The primary end point, a composite of death, stroke, or cardiovascular events requiring surgery occurred in 10.9% and 11.8% respectively in the two groups (P = 0.0012) for non-inferiority. The median number of in-office follow-ups was 0.5 in the remote follow-up group and 2.01 in the conventional in-office follow-up per patient year (P < 0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable.   In our next paper, Sarah Strand and associates use fetal magnetocardiography from the University of Wisconsin biomagnetism laboratory to study 39 fetuses with pathogenic variants in long QT syndrome, LQTS genes. 27 carried the family variant, 11 had de novo variants, and one was indeterminant. De novo variants, especially de novo SCN5A variants were strongly associated with a severe rhythm phenotype and perinatal death. Nine or 82% showed signature LQTS rhythms, six showed torsade de pointes, five were still born, and 9% died in infancy. Those that died exhibited novel fetus rythms, including AV block with 3:1 conduction ratio, QRS alternans in 2:1 AV block, long cycle length, torsade de pointes, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with torsade de pointes and perinatal death. Fetuses with familiar variants showed a lower incidence of signature LQTS rhythm, six out of 27 or 22%, including torsade de pointes, and 3 out of 27 or 11% all were live born. The authors concluded that the malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth.   In our next paper, Corina Schram-Serban and associates compare the severity of extensiveness of conduction disorders between obese patients and non-obese patients measured at high resolution scale. They studied 212 patients undergoing cardiac surgery (male:161, mean 63 years of age), who underwent epicardial mapping of the right atrium, Bachmann's bundle, and left atrium during sinus rhythm. Conduction delay [CD] was defined as interelectrode conduction time seven to 11 milliseconds and conduction block [CB] as conduction time ≥ 12 milliseconds. In obese patients, the overall incidence of conduction delay was 3.1% versus 2.6% (P = 0.002), conduction block 1.8% versus 1.2%, and continuous CDCB 2.6% versus 1.9% higher in the obese patients, conduction delay (P = 0.012) and continuous CDCB lines are longer. There were more conduction disorders at Bachman's bundle, and this area has a higher incidence of conduction delay 4.4% versus 3.3% (P = 0.002), conduction block 3.1% versus 1.6% (P < 0.001), continuous conduction block conduction delay 4.6% versus 2.7% and longer conduction delay or conduction delay conduction block lines. Severity of conduction block is also higher, particularly in the Bachmann bundle and pulmonary vein areas. In addition, obese patients have a higher incidence of early de novo postoperative atrial fibrillation. Body mass index and the overall amount of conduction block were independent predictors for the incidents of early postoperative atrial fibrillation.   In our next paper, Ricardo Cardona-Guarache and associates describe five patients with concealed, left-sided nodoventricular in four patients and nodofascicular in one patient accessory pathways. They proved the participation of accessory pathway in tachycardia by delivering His-synchronous premature ventricular complexes that either delayed the subsequent atrial electrogram or terminated the tachycardia, and by observing an increase in ventricular atrial interval coincident with left bundle branch block in two patients. The accessory pathways were not atrioventricular pathways because the septal ventricular atrial interval during tachycardia was less than 70 milliseconds in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing.   Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of accessory pathways was suspected after failed ablation of the right inferior extension of the AV node in 3 cases and by observing VA increase in left bundle branch block in 2 cases. The nodofascicular in 3 of the 4 nodoventricular accessory pathways were successfully ablated from within the proximal coronary sinus guided by recorded potentials at the roof of the coronary sinus, and nodoventricular accessory pathway was ablated via a transseptal approach near the coronary sinus os.   In our next paper, Pierre Qian and associates examined whether an open irrigated microwave catheter ablation can achieve deep myocardial lesions endocardially and epicardially through fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters.   In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patients), whereas 6 patients had PVC induced ventricular fibrillation, VT (29%), and VT could not be induced in 2 patients (9%). Activation mapping was possible in all 13 patients with inducible clinical VTs, substrate modification was performed in 15 patients with scar in 79%. After ablation and scar modification, the arrhythmia was noninducible in 19 patients (91%). Seventeen (81%) were eventually weaned off mechanical support successfully with the majority of patients being discharged home and surviving beyond one year. However, 6 (29%) died during the index admission with persistent cardiogenic shock.   In a research letter, Parveen Garg and associates examined the multi-ethnic study of atherosclerosis [MESA] incident atrial fibrillation a population with 50% African-American or Hispanic. After adjusting for age, race, ethnicity, sex education, income, clinic site, height, body, mass index, cigarette, smoking, diabetes, systolic and diastolic blood pressure, and hypertensive medications, physical activity, alcohol consumption, lipid parameter to lipid lowering therapy, the baseline lipoprotein A level greater or equal to 30 milligram per deciliter was inversely associated with developing atrial fibrillation compared those with lower levels (hazard ratio 0.84). However, the mechanism of this paradoxical association is unclear.   In another research letter, Yoshihide Takahashi and associates reported that 49 patients undergoing ablation of persistent atrial fibrillation had at least one focal site and rotational activation in 57%. Of these, 19 patients underwent a repeat ablation for recurrent atrial fibrillation. AF was mapped in 17 patients and 131 focal activation sites were ablated. There were 105 displayed focal activation sites during the de novo ablation and 89 focal activation sites during the repeat ablation. During the de novo ablation, rotation activation was observed in 19 sites. Of the 19 sites, 12 (63%) displayed rotational activity, also with the repeat ablation. The author suggested focal or rotational activation sites can be classified into two types, ones critical for AF recurrence and the ones that are bystander.   That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.   This program is copyright American Heart Association, 2020.   Correction: In the study by Pierre Qian and associates, the epicardial ablations via subxiphoid access were performed in sheep, not pigs, as previously stated.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue.                                                 In our first paper, in a single‐center observational cohort study, Owen Donnellan and Associates compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery, with those of non-obese patients following atrial fibrillation ablation. In addition to morbidly obese patients who did not undergo bariatric surgery, they matched 51 morbidly obese patients' body mass index, 40 kilograms per meter squared, who had undergone prior bariatric surgery in a two to one manner with 102 non-obese patients, and 102 morbidly obese patients without bariatric surgery on the basis of age, gender, and timing of atrial fibrillation ablation. From the time of bariatric surgery to ablation, bariatric surgery was associated with a significant reduction in BMI. 47.6 to 36.7 and reduction in systolic blood pressure, 145 to 118, P < 0.001.                                                 During a mean follow up of 29 months following ablation, recurrent arrhythmia occurred in 10 out of 51 or 20 patients in a bariatric surgery group, compared to 25 out of 102 patients, 24.5% in a non-obese group, and 56 out of 102 or 55% in the non-bariatric surgery morbidly obese group. No procedural complications were observed in the bariatric surgery group. In our next paper, Martin Andreas and Associates examined whether noninvasive, low-level, transcutaneous electrical stimulation of the greater auricular nerve reduced the risk of postoperative atrial fibrillation, in a pilot of patients undergoing cardiac surgery. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation, amplitude 1-million-amp frequency, one Hertz for 40 minutes, followed by a 20-minute break, was performed for up to two weeks after cardiac surgery. Patients were randomized into sham, N equals 20 or treatment group, N equals 20, for low- level, transcutaneous electrical stimulation. Patients receiving low-level, transcutaneous stimulation had a significant reduced incidence of postoperative atrial fibrillation. Four out of 20, compared to controls 11 out of 20. P equals 0.02.                                                 The median duration of postoperative atrial fibrillation was comparable between the treatment group and control group. No effect on low-level stimulation on CRP or IL-6 levels was detectable. In our next paper, Kazuki Iso and Associates examine whether the vagal response phenomenon is common to patients without atrial fibrillation. Continuous, high- frequent stimulation of the left atrial ganglion and plexus was performed in 42 patients, undergoing ablation for atrial fibrillation. In 21 patients undergoing ablation for left-sided accessory pathway, the high frequency stimulation, 20 Hertz at 25 milliamps of 10 millisecond pulse duration, was applied for five seconds at three sites within the presumed anatomical area of each of the five major left atrial ganglion plexus, for a total of 15 sites per patient. The authors define vagal response to high frequency stimulation, as prolongation of the R interval by > 50% in comparison to the mean pre-high-frequency stimulation RR interval, average over 10 beats.                                                 In active ganglion plexus areas, is areas in which vagal response was elicited. Overall, more active ganglion plexi or GP areas were found in the atrial fibrillation group patients, than in the non-atrial fibrillation group patients. And in all five major GPS, the maximum R interval during high-frequency stimulation was significantly prolonged in atrial fibrillation patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of atrial fibrillation. The authors concluded that the significant increase in vagal responses elicited in patients with atrial fibrillation, compared to responses in non-atrial fibrillation patients, suggests that the vagal responses is to hypercan stimulations, reflect an abnormally increased ganglion plexi activity, specific to atrial fibrillation substrates.                                                 In our next paper, Vidal Essebag and Associates combine the data from the Bruise Control One and Two studies to evaluate the effect of concomitant antiplatelet therapy on clinically significant hematomas, and to understand the relative risk of clinically significant hematomas in patients treated with DOAC versus continued Warfarin. The Bruise Control study demonstrated that perioperative Warfarin continuation, reduced clinically- significant hematomas by 80%, compared to Heparin bridging. 3.5% versus 16%. Bruise Control Two observed a similarly low risk of clinically-significant hematomas when comparing continued versus interrupted direct oral anticoagulant. 2.1% in both groups. A total of 1,343 patients were included in Bruise Control One and Bruise Control Two, the primary outcome for both trials with clinically-significant hematomas. There are 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. Anti-platelet use versus non-use was associated with clinically-significant hematomas in 9.8% versus 4.3%. P less than 0.001 and remained a strong independent predictor with multi-variate adjustment. Odds ratio 1.965, however, multivariate analysis adjusting for anti-platelet use, there was no significant difference in clinically-significant hematomas observed between direct oral anticoagulant use, compared with continued Warfarin.                                                 In our next paper, Markus Rottmann and associates examine the relationship between activation slowing during sinus rhythm, and vulnerability for reentry, and correlated the areas with components of the circuit. In a porcine model of healed infarction, of 15 swine, nine had inducible ventricular tachycardia, 5.2 per animal. While in six swine, VT could not be induced despite stimulation from four RV and LV sites at two drive trains in six extra stimuli down to refract refractoriness. Infarcts with ventricular tachycardia had a greater magnitude of activation slowing, during sinus rhythm, a minimal endocardial activation velocity cutoff, less than 0.1 meters per second. Differentiated inducible from non-inducible infarctions. P equals 0.15. Regions of maximal endocardial slowing during the sinus rhythm corresponded to the VT isthmus. Area under the curve equals 0.84 while bystander sites exhibited near normal activation during sinus rhythm. VT circuits were complex, with 41.7 exhibiting discontinuous propagation with intramural bridges of slow conduction in delayed quasi -simultaneous endocardial activation. Regions forming the VT isthmus borders had facts or activation during sinus rhythm, while regions forming the inner isthmus were activated faster during ventricular tachycardia.                                                 In our next paper, Mary Rooney and Associates sought to define the prevalence of subclinical atrial fibrillation in a community-based elderly population, and to characterize subclinical atrial fibrillation and the incremental diagnostic yield of four versus two weeks of continuous ECG monitoring. They conducted a cross-sectional analysis within the community- based, multi-centered observational atherosclerosis risk in communities. Erik Study, using visit five, 2016 to 2017 data. The 2,616 Erik Study participants who wore a lead-less ambulatory ECG monitor for up to two weeks were age 79 years, 42% men and 26% black. In its subset, 386 participants without clinically-recognized atrial fibrillation wore the monitor twice, each time for two weeks. They characterize the prevalence of subclinical atrial fibrillation, atrial fibrillation detected without clinically recognized atrial relation. Over two weeks of monitoring and the diagnostic yield of four versus two weeks, the authors found that the prevalence of subclinical atrial relation was 2.5%. the prevalence of subclinical each relation was 3.3% among white men, 2.5% among white women, 2.1% among black men and 1.6% among black women.                                                 Subclinical A Fib was mostly intermittent, 75%. Among those with intermittent subclinical atrial fibrillation, 91% had an AF burden of less than or equal to 10%, during the monitoring period. In a subset of 386 patients without clinical atrial fibrillation, 78% more subclinical atrial fibrillation was detected by four weeks versus two weeks of ECG monitoring. In this study, the prevalence of subclinical A Fib was lower than previously reported. And monitoring beyond two weeks provided substantial incremental diagnostic yield.                                                 In our next study, Rafael Ramirez and Yoshio Takemoto and Associates investigated arrhythmic mechanisms of Ranolazine in sheet models, in paroxysmal and persistent atrial fibrillation. Paroxysmal atrial fibrillation was maintained during acute stretch and persistent atrial relation was induced by long-term atrial tachypacing. Isolated Langendorff-perfused sheet parts were optically mapped. In paroxysmal atrial fibrillation, Ranolazine 10 micromolar reduced dominance frequency from 8.3 to 6.2 Hertz. P less than 0.01, before converting to sinus rhythm, decreased singularity point density for 0.07 to 0.039 and left atrial epicardium and prolonged atrial fibrillation cycling. Road or duration tip trajectory in variants of Afib cycle lengths were unaltered. In persistent atrial fibrillation, Ranolazine reduced dominance frequency, prolonged atrial fibrillation cycle length, increased the variance of atrial fibrillation cycling and had no effect on singularity point density, and failed to convert atrial fibrillation to sinus rhythm. Doubling the Ranolazine concentration or supplementing with Dofetilide failed to convert persistent atrial fibrillation to sinus rhythm.                                                 In computer simulations or rotors, reducing the sodium current decreased dominant frequency, increased tip meandering, and produce vortex shedding upon wave interaction with un-excitable regions. Thus, the authors concluded that paroxysmal atrial fibrillation and persistent atrial relation respond differently to Ranolazine. Cardioversion in the paroxysmal atrial fibrillation can be attributed partly to decrease dominant frequency and singularity point density and prolongation of atrial fibrillation cycling. In persistent atrial fibrillation, increased dispersion of atrial-like cycle length and likely vortex shedding, contributes to rotor formation, compensating for any rotor loss, and may underline the inefficacy of Ranolazine to terminate persistent atrial fibrillation.                                                 In our next paper, Pyotr Platonov and Associates assess the risk of atrial fibrillation and its relationship to Long-QT syndrome genotype, and the long-term prognosis in Long-QT syndrome patients. Genotype- positive patients with Long-QT syndrome. 784 with LQT1. 746 with LQT2, and 233 with LQT3, were compared with 2043 genotype-negative family members. In patients followed from birth to 60 years, LQT3 patients had an increased risk of atrial fibrillation compared to genotype-negative family members. Hazard ratio 6.62. While neither LQT1 or LQT2 demonstrated increased atrial fibrillation risk. After the age of 60 years, LQT2 patients had significant lower risk of atrial fibrillation compared with genotype-negative controls. Hazard ratio of 0.07. Atrial fibrillation was a significant predictor of cardiac events in LQT3 patients, through the age of 60. Hazard ratio, 5.38. The authors concluded that there's an increased risk of early-age atrial fibrillation in LQT3 patients and a protective effect of LQT2 genotype, resulting in a decreased risk of atrial fibrillation after the age of 60.                                                 In our next paper, Julia Ramírez and Associates evaluated the cardiovascular prognostic value of T-waves morphology restitution in 55,222 individuals undergoing an exercise stress test in the UK biobank, and identify any genetic contribution. They found that 1,743 or 3.2% of individuals had a cardiovascular event. T-wave morphology restitution during recovery from exercise was significantly associated with cardiovascular events. Hazard ratio 1.11. Independent of clinical variables and other ECG markers, T-wave morphology restitution during recovery from exercise was also associated with all-cause mortality. Hazard ratio 1.1. And ventricular arrhythmias, hazard ratio 1.16. They identified 12 genetic loci, in total for T-wave morphology restitution during exercise, in T wave morphology restitution during recovery, of which nine are associated with another ECG marker. Individuals with the top 20% of T-wave morphology restitution during recovery, genetic risk scores, were significantly more likely to have a cardiovascular in the full UK biobank. 5.3% than individuals in the bottom percent, a 20% hazard ratio of 1.07.                                                 We have two other research letters in a special report. Wassim Mosleh, Sharma Kattel report that Galectin-3 is a predictor of mortality after cardiac arrest. In the next research letter, Jerry Jez and Associates report on remotely-navigated ablations in ventricular myocardium, that result in acute lesion-size, comparable to force sensing manual navigation. In a special report, Sohaib Virk and Saurabh Kumar report on a meta-analysis of remote magnetic versus manual catheter navigation for atrial fibrillation ablation. That's it for this month. We'll hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright, American Heart Association 2019.  

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                 In our first paper, Mark McCauley, Flavia Vitale and associates report that carbon nanotube fibers may improve impaired myocardial conduction. In three sheep, radiofrequency ablation was used to create epicardial conduction delay. In addition, in a rodent model, carbon nanotube fibers were sewn across the atrial ventricular junction. They demonstrated acute ventricular preexcitation, but in chronic studies at four weeks, atrial pacing was required for resumption of AV conduction. Carbon nanotube fibers are conductive, biocompatible with no gross or histopathological evidence of toxicity.                                                 In our next paper, Koichiro Ejima and associates compared outcomes of circumferential pulmonary vein isolation for atrial fibrillation ablation randomized to contact force monitoring or unipolar signal modification in 136 patients with paroxysmal atrial fibrillation. In the unipolar signal modification-guided group, each radiofrequency application was delivered until the development of completely positive unipolar electrograms. In the contact force monitoring-guided group, a contact force of 20 grams, ranged 10 to 30 grams, and a minimum force time integral of 400 gram seconds were the targets for each radiofrequency application. The freedom from atrial tachyarrhythmia recurrence at 12 months was 85% in the unipolar signal modification-guided group and 70% in the contact force monitoring-guided group, P equals 0.031. The radiofrequency time for pulmonary vein isolation was shorter in the unipolar signal modification-guided group than contact force monitoring-guided group, but was not statistically significant, P equals 0.077. The incidence of time-dependent in ATP-provoked early electrical reconnections between the left atrium and pulmonary veins, procedural time, fluoroscopic time, and average force-time integral did not significantly differ between the two groups.                                                 In our next paper, Vishal Luther and associates tested whether ripple mapping is superior to conventional annotation-based local activation time mapping for atrial tachycardia diagnosis. Patients with atrial tachycardia were randomized, either ripple mapping or local activation time mapping. The primary endpoint was atrial tachycardia termination with delivery of the planned ablation lesion set. The inability to terminate atrial tachycardia with the first lesion set, the use of more than one entrainment maneuver, or the need to cross over to the other mapping arm were defined as failure to achieve the primary endpoint. The primary endpoint occurred in 38 of 42 patients or 90% in the ripple mapping group, and 29 of 41 patients, 71%, in the local activation time mapping group, P equals 0.45. The primary endpoint was achieved without any entrainment in 31 out of 42 patients or 74% with ripple mapping, and 18 out of 41 patients or 44% with local activation time mapping, P equals 0.01. Of those patients who failed to achieve the primary endpoint, atrial tachycardia termination was achieved in 9 out of 12 patients or 75% in the local activation time mapping group following crossover to ripple mapping with entrainment, but zero out of four patients, 0%, in ripple mapping group crossing over to local activation time mapping with entrainment, P equals 0.04.                                                 In our next paper, Franziska Fochler and associates examined whether anatomical targeting of late gadolinium enhancement MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent atrial arrhythmias post-atrial fibrillation ablation. The authors studied 102 patients who underwent initial atrial fibrillation ablation and repeat ablation for recurrent atrial arrhythmias within one-year. 46 patients or 45% with atrial fibrillation recurrence were assigned to group one and underwent fibrosis homogenization as the second procedure. 56 patients or 55% with atrial tachycardia recurrence were assigned to group two and underwent late gadolinium enhancement MRI detected scar-based dechanneling. Both groups underwent re-isolation of pulmonary veins, if necessary.                                                 In the first 25 patients from group two, the atrial tachycardia was electroanatomically mapped and a critical isthmus was defined. It was found that those isthmi were located in the regions with non-transmural scarring detected by late gadolinium enhancement MRI. In the last 31 patients from group 2, an empirical late gadolinium enhancement MRI-based dechanneling was performed solely based on late gadolinium enhancement MRI results. During one-year follow-up after the second ablation, 67% of patients group one and 64% of patients group two were free from occurrence. In group two, 64% in the electroanatomic-guided and 65% in the late gadolinium enhancement MRI dechanneling group were free from recurrence. The authors concluded that homogenization of existing scar is appropriate treatment for recurrent atrial fibrillation while dechanneling of existing isthmi seem the appropriate approach for patients recurring with atrial tachycardia.                                                 In our next paper, George Leef, Fatemah Shenasa, Neal Bhatia and associates examined whether wave front field mapping of persistent atrial fibrillation can reveal an underlying network of a small number of spatially anchored rotational and focal sites. They examined unipolar atrial fibrillation electrograms from 64-pole baskets in 54 patients from an international registry in whom persistent atrial fibrillation was terminated by targeted ablation. They identified 4.0, plus or minus 2.1, spatially anchored rotational focal sites in atrial fibrillation that were a single in seven patients type I or paired chiral-antichiral type II rotational drivers that controlled most of the atrial area. Ablation of one or two large drivers terminated all cases of these types of atrial fibrillation. Third, interaction of three to five drivers type III, n equals 42, was present with changing areas of control. Targeted ablation at driver center terminate atrial fibrillation and required more ablation in type III versus I, P equals 0.02 in the left atrium.                                                 In our next paper, Ryan Azarrafiy and associates examined survival after superior vena cava tear using an endovascular balloon. Data were prospectively collected from both a United States Food and Drug Administration-maintained database and physician reports of adverse events as they occurred. Confirmed superior vena cava tears were analyzed for patient demographics, case details, and index hospitalization mortality. Over a period of two years, 116 confirmed superior vena cava events were identified, of which 44% involve proper balloon use and 50% involve no use or improper use. When an endovascular balloon was properly used, 45 of 51 patients, or 88.2%, survived in comparison to 37 out of 65, or 56.9%, when a balloon was not used or improperly used; P equals 0.0002. Furthermore, multivariate regression modeling found that proper balloon deployment was an independent, negative predictor of in-hospital mortality for patients who experienced a superior vena cava laceration, odds ratio of 0.13; P value less than 0.001.                                                 In our next paper, Bharatraj Banavalikar and associates examined 28 patients with focal atrial tachycardia, mean age 34.6 years, females 60.7%, were included in the study. Most common symptoms were palpitations, 85.7%, followed by shortness of breath, 25%. The mean atrial tachycardia rate was 170 beats per minute and mean left ventricular ejection fraction was 54.7%. Overall, 18 or 64.3% patients responded within six hours of the first dose of ivabradine; 13 out of the 18 ivabradine responders subsequently underwent catheter ablation. Focal atrial tachycardia originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites, P equals 0.46.                                                 In our next paper, Takumi Yamada and associates studied 26 consecutive patients with idiopathic origins that were identified at the left ventricular summit. The authors studied 26 consecutive patients with idiopathic left ventricular summit ventricular arrhythmias in the basal and apical left ventricular summit in 15 and 11 patients, respectively. Radiofrequency ablation of the apical left ventricular summit ventricular arrhythmias were successful in the great cardiac vein in nine patients and in the apical left ventricular outflow tract in two. Ablation of the basal left ventricular summit was successful in the aortomitral continuity in nine patients, at the junction of the left and right coronary cusp in 4 and the left coronary cusp in two. Three apical left ventricular summit ventricular arrhythmias exhibited an eccentric endocardial pattern that was from basal to apical left ventricular outflow tract. In 11 basal left ventricular summit ventricular arrhythmias, the activation pattern was eccentric because ventricular activation within the great cardiac vein in the apical left ventricular summit was earlier than that in the basal left ventricular outflow tract. In two left ventricular summit ventricular arrhythmias, the activation was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site. The authors concluded that eccentric activation patterns often occurred during idiopathic left ventricular, ventricular arrhythmias, which could mislead catheter ablation of those arrhythmias.                                                 In our next paper, Anand Thiyagarajah and associates performed a systematic review and meta-analysis of studies performing posterior wall isolation for atrial fibrillation. Of 17 studies, 13 employed box isolation, 3 single ring isolation, and 2 debulking ablation, and included 1,643 patients, of which 31% had paroxysmal atrial fibrillation. The acute procedural success for achieving posterior wall isolation was 94%. Single-procedure 12-month freedom from atrial arrhythmias was 65% overall and 61.9% for persistent atrial fibrillation. Randomized control trials comparing posterior wall isolation to pulmonary vein isolation, three studies in 444 patients, yielded conflicting results and could not confirm incremental benefit to posterior wall isolation; 15 major complications, 0.1%, including two atrio-esophageal fistulas, were reported.                                                 In a research letter, Tadashi Hoshiyama and associates examined the effect of contact vector direction on the ability of pulmonary vein isolation. In a review article, Belinda Gray and associates describes sudden cardiac death in the young, ages 35 years or less. A significant proportion of sudden cardiac deaths in this group may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmic syndromes. Tragically, sudden deaths may be the first manifestation of disease in a family. Both clinical and genetic evaluation of surviving family members becomes important.                                                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.                                                 This program is copyright American Heart Association 2019.  

Paul Wang:         Welcome to the monthly podcast On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Moo-Nyun Jin, Tae-Hoon Kim, and associates examined the 1-year serial changes in cognitive function, with or without atrial fibrillation catheter ablation. They used the Montreal cognitive assessment score in 308 patients undergoing atrial fibrillation ablation, the ablation group and 50 atrial fibrillation patients on medical therapy who met the same indication for atrial fibrillation ablation, the control group at baseline three months and 12 months. Cognitive impairment was defined as a published cutoff score of less than 23 points. Pre-ablation cognitive impairment was a detected in 18.5%. The Montreal cognitive assessment score significantly improved one year after radio frequency ablation. In both the overall ablation group, 24.9 to 26.4 p less than 0.001, and the propensity matched ablation group 25.4 to 26.5, but not in the control group. 25.4 to 24.8 p equals 0.012. Pre-ablation cognitive pyramid odds ratio 13.7, was independently associated with an improvement in one-year post ablation cognitive function. In our next paper, Zian Tseng, James Salazar and associates studied World Health Organization defined sudden cardiac deaths autopsied in the POstmortem Systemic InvesTigation of sudden cardiac death, the POST SCD study to determine whether premortem characteristics could identify autopsy defined sudden arrhythmic death among presumed sudden cardiac deaths. They prospectively identified 615 World Health Organization defined sudden cardiac deaths, of which 144 were witnessed. Autopsy defined sudden arrhythmic death had no extra cardiac or acute heart failure cause of death. Of the 615 presumed sudden critic deaths, 348 or 57% were autopsy defined, sudden arrhythmic deaths. For witness cases, using an emergency medical system model area under the receiver operator curve 0.75, included presenting rhythm of ventricular tech or cardiac fibrillation, pulseless electrical activity, while the comprehensive model, adding medical record data and depression, area under the curve 0.78. If only VTVF witness cases, 48 of those were classified as sudden arrhythmic death. The sensitivity was 0.46, and specificity 0.90. For unwitnessed cases, the emergency medical system model, area under the curve 0.68, included black race, male sex, age, time since last seen normal, while the comprehensive, area into the curve 0.75, added the use of beta blockers, antidepressants, QT prolonging drugs, opiates, illicit drugs and dyslipidemia. If only unwitnessed cases, less than one hour, n equals 59, were classified as sudden arrhythmic deaths, the sensitivities were 0.18, and specificity was 0.95. The authors concluded that models could identify pre-mortem characteristics to better specify autopsy defined sudden arrhythmic deaths, among presumed sudden cardiac arrests. The authors suggest that the World Health Organization definition can be improved by restricting witnessed sudden cardiac deaths to ventricular tachycardia fibrillation or non-pulseless electrical activity rhythms in unwitnessed cases to less than one hour since last normal, at a cost of sensitivity. In our next paper, Rafael Jaimes III and associates performed optical mapping of trends, membrane, voltage and pacing studies on isolated Langendorff-perfused rat hearts to assess the cardiac electrophysiology after mono-2-ethylhexyl phthalate, a phthalate with documented exposure in intensive care patients. The authors found that a 30-minute exposure to mono-2-ethylhexyl phthalate increased the atrioventricular node effector in period 147 milliseconds compared to 170 milliseconds in controls and increased the ventricular effective refractory periods of 117 milliseconds compared to 77.5 milliseconds in controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths. Mono-2-ethylhexyl phthalate exposure also slowed epicardial conduction velocity, 25 centimeters per second compared to 60 centimeters per second in controls. The authors concluded that acute mono-2-ethylhexyl phthalate exposure, at clinically relevant doses, has a significant effect on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications and lead to cardiac arrhythmias. In our next paper, Stephan Willems and associates report the use of a novel, non-contact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measure timing and density of dipolar, ionic activation or charge density across the myocardium to guide ablation of atrial arrhythmias. They conducted a prospective non-randomized study, the UNCOVER AF trial which was conducted at 13 centers across Europe and Canada. In 127 patients with persistent atrial fibrillation who underwent mapping and catheter ablation, acute procedural efficacy of 98% was seen. At 12 months, the single procedure freedom from atrial fibrillation, on or off antiarrhythmic drugs, was 72.5%, with 23% undergoing retreatments following one or two procedures. Freedom from atrial fibrillation was 93.2%. The primary safety outcome was 98% was no device related major adverse events reported. In our next paper, Anne-Floor Quast, Niek Beurskens, and associates describe a novel, completely extracardiac pacing system, with a lead in the anterior mediastinum, outside the pericardium and circulatory system. A total of 166 or 95% out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. Access to the targeted implant location using delivery tool was successful in all five cadavers and three humans, without use of fluoroscopy, with an average lead delivery time of 121 seconds. No damage to the lung, pericardium, heart or internal thoracic vessels occurred. Pacing performance in six human subjects showed a voltage threshold of 4.7 volts in a threshold pulse width of 1.8 milliseconds. In our next paper, Yasuhiro Shirai and associates compare the ability to identify ventricular tachycardia isthmuses in ischemic and nonischemic cardiomyopathies. Of 445 patients, 228 with ischemic cardiomyopathy and 217 with nonischemic cardiomyopathy, undergoing VT ablation. Detailed entrainment mapping of at least one tolerated VT was performed in 111 patients, 71 with ischemic cardiomyopathy and 40 with nonischemic cardiomyopathy. Of 89 nonischemic cardiomyopathy VTs, the isthmus could be identified by endocardial entrainment in 55 or 62%, compared to only eight out of 47 or 17% nonischemic cardiomyopathy VTs, p less than 0.01. With combined endocardial and epicardial mapping, the isthmus could be identified in 56 or 63% ischemic cardiomyopathy VTs, and 12 or 26% of nonischemic cardiomyopathy VTs, p less than 0.01, while a similar proportion of patients any critical component, defined as entrance, isthmus or exit, could be identified in 85% of ischemic cardiomyopathy VTs and 79% of nonischemic cardiomyopathy VTs, p equals 0.3. Complete success, no inducible VT at the end of the procedure was 82% versus 65%, p equals 0.04 and a one-year single procedure VT survival, 82% versus 55%, p less than 0.01. Both higher in patients with ischemic cardiomyopathy. The authors concluded that among mappable ischemic cardiomyopathy VTs, critical circuit components can be usually identified on the endocardium. In contrast, among mappable nonischemic cardiomyopathy VTs, although some critical components can be typically identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location. In our next paper, Miki Yokokawa and associates targeted documented but non-inducible clinical VTs, based on stored, implantable cardioverter defibrillator electrograms. Radio frequency ablation was performed in a consecutive group of 66 postinfarction VTs, in whom clinical VTs were non-inducible during an ablation procedure. In the first 33 patients, the control group, only inducible VTs were targeted. In the second 33 patients, non-inducible clinical VTs were targeted by pace mapping based on stored ICD-electrograms, the ICD electrogram guided ablation group. VT recurred in five patients or 15% in the ICD-electrogram guided approach, and in 13% or 39% in the control group. Freedom from recurrent VT was higher, p equals 0.04, in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or total mortality between groups. In our next paper, Albert Feeny and associates examined whether machine learning could predict cardiac resynchronization therapy or CRT response. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprise the testing cohort. Response was defined as greater than or equal to 10% increase in left ventricular ejection fraction. Machine learning models were developed to predict CRT response using different combinations of classification algorithms in clinical variable sets on the training cohort. 925 patients were included. On the training cohort, the best machine learning model was a naive Bayes classifier using nine variables, QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial LV lead. On the testing cohort, machine learning demonstrated better response prediction than guidelines, area under the curves 0.7 versus 0.65, p equals 0.012, and greater discrimination of event-free survival, concordance index 0.61 versus 0.56, p less than 0.001. The fourth quartile of machine learning model had greatest risk of reaching the composite endpoint, while the first quartile had the least, hazard ratio of 0.34, p less than 0.001. The authors found that machine learning with nine variables incrementally improved prediction of CRT response and survival beyond guidelines, but its performance with not improved by incorporating more variables. In our next paper, Bernhard Kaess, Charlotte Andersson and associates examine the familial clustering of cardiac conduction defects in the Framingham heart study, using multivariable-adjusted logistic regression models to investigate the association of parental AV block, complete bundle branch block, or a pacemaker insertion with occurrence of cardiac conduction abnormalities on offspring. Individuals with at least one effected parent with a conduction defect had at 1.65-fold odds for manifesting AV block, and 1.62-fold odds for developing complete bundle branch block. If at least one parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had 1.62-fold odds for experiencing any of these conditions. The Danish and nationwide administrative registries of nearly 3 million individuals and about five thousand incident pacemaker implantations, individuals with at least one first degree relative with a history of pacemaker insertion, had a multivariable-adjusted 1.68-fold incident rate ratio of undergoing pacemaker insertion. If the affected relative was less than or equal to 45 years of age, the incident rate ratio was markedly increased to 51.0. In our final paper, a review article, Venkat Nagarajan, Siew Ho Yen, and Sabine Ernst provide a detailed discussion of anatomic landmarks and considerations that will aid in his bundle pacing lead implantation. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.  

Dr Amit Khera:                  Welcome to Circulation On The Run. Our weekly podcast summary and backstage pass to the Journal. I'm Dr Amit Khera, associate editor and digital strategies editor from UT Southwestern Medical Center in Dallas, and I had the distinct privilege of standing in for Dr Carolyn Lam and Greg Hundley this week. Twice a year, we are very fortunate to have some unique podcasts when we don't have circulation issues, and in the past we've met with many fellows in training and heard about some interesting studies that they're doing. Today we have a very special podcast we have not done before, and that is one where we had the opportunity to learn about our Circulation Family of Journals, and more importantly to hear from the dynamic editors in chief of these various journals. I think you're really going to enjoy it, we'll walk through and hear from each one of them, hear about some of the innovative things that are happening, some of the future that they see for their journal in their field, and I really enjoyed it, and I'm sure you will as well. So, without further ado, we'll start with our first editor. Dr Sunil Rao:                      I'm Sunil Rao. I'm an intervention cardiologist at Duke, and I'm the Editor-in-Chief for Circulation Cardiovascular Interventions, which is one of the daughter journals of the Circulation Family. We publish articles really related to the broad spectrum of interventional cardiology, from coronary interventions to peripheral arterial disease, and Endovascular interventions to structural heart disease interventions. We also published review articles in all of those areas, as well as any health policy or outcomes studies that are in that space. Dr Amit Khera:                  Tell us what are some of the innovative things that your journal is doing this year. Dr Sunil Rao:                      We're really excited about two things, one is our extremely successful Assistant Editor program that we launched last year at A.H.A. 2018. This is a program where we have five early career individuals that are within five years of completing their fellowship program who joined the editorial team at Circulation Cardiovascular interventions, and in that role they really learn a lot about the mechanics of how scientific publishing works, they commit to doing manuscript reviews, and receive feedback on improving their peer review process, and even independently handles some manuscripts as well, that are in their areas of interest. This is our way, I think, of encouraging the next generation to stay engaged with science, and with the scientific publishing process. It's been extremely successful. Assistant editors are part of our team for a two year term. So, in 2020, we will be selecting the next class of assistant editors, and after their term is ended, they join our editorial board as editorial board members. So, we're really excited about that, it's been an overall positive experience, for I think everybody involved. The second thing that we're really excited about is that we launched a social media presence for the journal, which it previously did not have. So, we have a very active Circulation Cardiovascular Interventions Twitter handle, I encourage all the listeners to join Twitter if you're not on Twitter, and if you are on Twitter please follow at Cirque intervened. It's " at C.I.R.C.I.N.T.V.". That is the official Twitter handle for our journal. Dave Fishman is our social media editor, and Chadi Alraies is our assistant social media editor, and we're not just tweeting out the articles, and providing summaries when the papers get published, we're holding Twitter journal clubs once a month ,and these have been extremely successful, it's an hour long Twitter journal club where the discussion gets very intense, and there's a lot of back and forth. We try to have the authors on as well, so that they can explain the rationale for their study, some of the challenges that they face when they are doing the study, and hopefully provide some implications for clinical practice, and what the next steps are. That's a way for us to engage our readership, it's almost a form of post publication peer review, which I think is becoming very popular. In addition, remember we don't have a print format of our journals, so this is a way to get the readership more engaged with the Web site, and to come to our website and learn what elsewhere publishing, and how they can get involve with the Journal as well, both as authors who submit their work, or if they want a peer review for us, please contact us and let us know. Dr Amit Khera:                  I really love hearing about the Twitter journal club, I know that they are well received, and certainly getting a lot of traction. Tell us about what initiatives or topics you're most excited about this year, and maybe some things that are coming later in the year. Dr Sunil Rao:                      We're really excited about the big areas in interventional cardiology, which are coronary physiology, we've published quite a few papers on looking at different physiological parameters, and how they can drive the appropriate use of PCI and how that affects outcomes. I think that's going to continue to be a huge topic over the next year, Certainly such a heart disease has exploded, and with the data on low risk patients undergoing TAVR, and having really good outcomes, we're seeing a lot more submissions in the low risk TAVR space, the other area that's really exploding right now is Mitral and Tricuspid Valve Interventions, one of the areas that I think has seen a tremendous amount of device innovation. So, we're seeing a lot of submissions from really high quality papers in that space, but I think it's also important to note, that unlike previous iterations of the Journal, we're actually having a review article, we're trying to have a review article every month on a major area that is burgeoning, so that the readership can understand the overall lay of the land, with respect to evidence, how that guy's clinical practice, and what's coming next. So, we've published quite a few review articles already, and there are more to come, and I think that's a really important way for the readership to keep current with what's going on in Interventional Cardiology. Dr Amit Khera:                  What about the advancing aspects of your subspecialty? There's so much going on in interventional cardiology, it's a bit dizzying, just tell us a little bit about some of the ways that your journal's helping advance that mission, not just now but perhaps in the future. Dr Sunil Rao:                      I think one of the challenges that we have at Interventional Cardiology, and maybe this is true across Cardiology, is that the evidence is developed very rapidly, and oftentimes it almost seems like the field is lurching back and forth in certain areas, a prime example of that is the drug coated balloon controversy for Peripheral Interventions. The Journal Of The American Heart Association published a meta-analysis, showing that there may be an association between the use of these devices and increased mortality, that has led to a lot of discussion in the interventional community, and quite frankly I think there's a fair amount of confusion out there about whether we should be using these devices, should we put a moratorium on these devices, is the signal real, if it is, what's the mechanism of death. So, a lot of conversation around that, in fact, it's led to what's going to be a focused FDA meeting in June, specifically on the drug coated balloon controversy. Where I see our journal playing a role is really in trying to, not only publish the latest science, which is rigorous in the field for controversial topics such as this, but also to help provide some context for that science, and I think our integrated strategy of original science review articles, and social media really helps us to communicate with the readership, and with the Interventional Cardiology community writ large, meaning not just physicians, but also Cath lab staff, nurses, noninvasive cardiologists who obviously have patients who are undergoing interventions, and even policymakers, to keep them abreast of what's going on, so that they can have the same level or base of knowledge, so that the conversation is on a level playing field. Dr Amit Khera:                  Okay, well you heard it from Dr Sunil Rao. Thank you for your time. Dr Kiran Musunuru:        I'm Kiran Musunuru, I'm the outgoing Editor-in-Chief of Circulation Genomic and Precision Medicine. Let me start by saying a little bit about the content of the journal, it considers all types of articles related to, as the name implies, Genomic and Precision Medicine, and more specifically, Clinical Genetics, the molecular basis of complex cardiovascular disorders, considered at a variety of levels, that can include a lot of different, what we would call Omics Techniques, from Genomics to Transcriptomics, Proteomics, Metabolomics, Metagenomics, and, so forth. It also deals with big data applications, that includes Electronic Health Record Data, Patient generated data combined with any of the things I've already mentioned, Genome Wide Association Studies, Pharmacogenomics, Gene Therapy, Therapeutic Gene Editing, Systems Biology. So, it's a pretty comprehensive look at all the various topics that would fall under the rubric of Genomic and Precision Medicine. Dr Amit Khera:                  Now, Dr Musunuru, you mentioned the outgoing Editor-in-Chief, let's introduce the incoming Editor-in-Chief, Thatcher Christopherson Semsarian. Dr Chris Semsarian:         I'm the incoming Editor-in-Chief. My name is Chris Semsarian, I'm a cardiologist at the Royal Prince Alfred Hospital in Sydney, Australia. Dr Amit Khera:                  What are some of the innovations you and the Journal are doing this year, or, what are some of the things you see coming in the future? Dr Kiran Musunuru:        Something I'm very excited about, is that we are just starting a pilot project with the American Heart Association's Institute for Precision Cardiovascular Medicine. The institute has a very nice platform called the Precision Medicine platform, and, in brainstorming last year, we realized there was a very nice opportunity to try to create a new type of journal article. There's also a big move in science nowadays to improve transparency, and rigor, and reproducibility, especially in science. The idea being that ideally other investigators should be able to take one team's work, and be able to run through the entire analytical process, and reproduce the original findings, and perhaps even find ways to improve upon those original findings, and, so we realized working with the institute's Precision Medicine Platform, we had the opportunity to actually make a new type of article, we think of, as the paper of tomorrow, a virtual article. The idea would be, that we would have primary data on the Precision Medicine Platform, the analytical tools used to process the data would also be on the Precision Medicine Platform, the analytical plan, in the form of a so-called Jupiter notebook, that basically takes people step by step through exactly which tools were used in which order, in which way, with which parameters, would be on the Precision Medicine Platform, and then there would be some verbal explanation, some background, to explain the context of these analysis, and to really put it into perspective, as how it fits into the body of literature, and so the idea would be, this would live on the Precision Map Platform in a virtual format, and then anyone else who is interested in this work could come, and actually directly interact with the data, and the tools, and the analytical plan, and could actually rerun the entire papers work from scratch, thus reproducing it, and then could actually tweak the analytical plan, or install tools of their own, and be able to build upon the work that had already been done. It's a very different way of thinking about journal articles, more as living entities rather than static work that just lives on a page, and is there as reported, and then never has an opportunity to be fully produced or improved upon. Dr Amit Khera:                  There's so much happening in the space of genomics, and obviously, we hear the word "Precision Medicine" so commonly. Tell us a bit about how your journal in specific is advancing the mission of your area. Dr Kiran Musunuru:        I'll say a little bit, and then maybe turn it over to Chris, give his perspective as the incoming Editor-in-Chief. I think it's a vibrant field, but it's also a very new field, it's evolving rapidly, and I think the Journal has a very important role to play, and not only reporting the results that are coming out of studies in this field, but actually having a role to play in helping to shape the field, helping to define the field, it's very exciting, it's very much in rapid evolution. Just ten years ago or so, when the Journal first started, we were just starting to see the first Genome Wide Association studies, and now we've gone so far beyond that.                                                 Now, again, we're talking about these large bio banks, we're talking about Precision Medicine, we're talking about applying this information in health care, we're talking about combining all of these various streams of data and many levels to be able to do studies, that are, I would even say, exponentially advanced beyond what we able to do just ten years ago, and so, it's very exciting times for the journal, then maybe I can ask Chris to share his thoughts on that. Dr Chris Semsarian:         Yeah Kiran, I mean, it's a great honor system to follow in your amazing footsteps, and what you've done for the Journal, and as the incoming Editor-in-Chief, I really want to sort of try, and build on the platform that you've established over the last few years, and really, one of the areas that I'm particularly interested in is the area of Translation of Genomic Findings. I mean, ultimately what we do in our lives, as clinicians, is to help patients improve diagnosis, to improve the treatment of these patients, and to be able to do studies with very basic understanding of how our genomes work, and how Narcotic Genes interact, and translating those findings into these improved diagnostic approaches, and even in guiding management is really exciting, I think, in terms of clinical medicine, and improving patient care as we look ahead. I really want to be able to continue to publish really, state of the art, novel, innovative, research areas, that you've already covered, Kiran, which would lead to better care of our patients, who are ultimately the beneficiaries of this type of amazing work.                                                 So, I'm really excited looking at the Journal, it's a tremendous area of interest and research, where there's twenty-two thousand genes approximately now genomes, and we really don't understand most of them in terms of their intricate function, and I figured it's a great time ahead, in terms of Precision Medicine. Dr Amit Khera:                  Okay, well, that was Dr Kiran Musunuru, and Christopher Semsarian, we appreciate both of your time today for Circulation on the Run. Dr Paul Wang:                   I'm Dr Paul Wang, I'm the Editor-in-Chief of Circulation Arrhythmia and Electrophysiology. Our Journal covers really the expanse of our field, going from basic mechanisms of arrhythmias, so very basic science work, to really clinical practice, clinical outcomes, to population based studies, and genetic based considerations in our field. So, we really feel we encompass the entire range, and there really isn't any topic within our area, that we don't feel is outside our realm. Dr Amit Khera:                  I know there's so many innovative things you're doing, Dr Wang, with your journal. Why don't you tell us a little bit about your plans for this year. Dr Paul Wang:                   We've been excited; our team has been at the Journal for two years now, and we focused on a number of different areas. So, I think one of our biggest advances, and we've tried to be more responsive to the authors, so we've really reduced the time to first decision very substantially, from over twenty days, to ten days or less, I think we hit a record of 7.8 days in the journal. So, really, we hope we're more responsive, we've involved the editorial board, we've substantially expanded it, so that more of our reviews of greater proportion going to our editorial board, which is a really fabulous, internationally recognized group, with really high quality reviews, so we've been very pleased, with both a level of science that we've received, as well as the level of the reviews that we have. One other area is, we really want to make sure that the reviewers, who do much of the heavy lifting, in addition to our editors for The Journal, and so we've established a new Reviewer Recognition Award System, they can be designated as silver, gold or platinum, and we've reached out to department chairs, or their deans, and recognizing that they won this prestigious award for their performance, and great work with the Journal, so there are a number of different things that, in fact, we think we've made some advances in, the other areas are really that of extending our reach, and so, one of the things we concentrated on, initially with the adding of podcasts, so we do that monthly.                                                 All the articles are now available in review, and then what we're starting at our new initiatives is, we'll be starting a Twitter Journal Club. I've been recording at least two of our articles, as the interview with the authors, and then we're going to be having a journal club, in which we will have the opportunity for people around the world to comment, and have a discussion that will really be exciting, we think. So, there are a number of other areas that we're thinking about, in terms of that kind of work. Dr Amit Khera:                  The field of Electrophysiology seems to be changing by the day, maybe you can tell us a little bit, about how the journal is advancing the mission of the field of electrophysiology. Dr Paul Wang:                   So, one of the things that we focused on is the role the Journal can play, in terms of connecting with other elements of our field, and one of the ways that we've really concentrated on is, in particular, working closely with the American Heart Association, and its committees. We're related to a number of committees, but particularly, there is a committee on Electrocardiography, Electrophysiology, part of the Clinical Cardiology Council, and so, we work very closely with that group, and, in fact, we've invited that group to create proposals for a number of review articles, state-of-the-art reviews, that we hope will come out in the next year or so. The ways in which we can tie together our committees to AHA overall, I think, is really the direction we're looking for our journal, and we feel we can play a very novel, and innovative role in that regard. We, for example, also reached out to the American Heart Association funded researchers in our area, and invited them to participate in the journal, participate in our committees, become fellows or FAHA's of the American Heart Association, so we really want to create this family, a real community, and sense of community, that we hope will stem from the Journal. So, we're very excited about the future, and what we might be able to achieve together. Dr Amit Khera:                  Thank you so much, Dr Paul Wang for your time today, and we appreciate your insights on Circulation, Arrhythmia and Electrophysiology. Dr Nancy Sweitzer:          Hi, I'm Nancy Sweitzer. I'm the Editor-in-Chief of the Journal Circulation Heart Failure. At Circ Heart Failure, we deal with all things related to heart failure. Heart failure is an expanding specialty, relatively new subspecialty in cardiology, and we're very interested in the physiology, and mechanisms of heart failure, as well as treatments of heart failure, and the innovative evolution of the specialty which includes Advanced Hemodynamics, Mechanical Circulatory Support, and transplant as therapies, as well as all Implanted Device Therapies, and new, and Innovative Pharmacologic, and Gene Therapies as well. Dr Amit Khera:                  Tell us a bit about initiatives, or features in Circulation Heart Failure, that you're planning on tackling not only this year, but into the future. Dr Nancy Sweitzer:          The effort we're most excited about at Circulation Heart Failure has been ongoing now for a little over a year, but continues, and is really focused on the emerging scientists in the Heart Failure Space; we call it our "Featured Emerging Investigator Spotlight", and this spotlight focuses on authors of manuscripts, who are within ten years of their terminal training, and can take full responsibility for the content of a manuscript. When we publish a featured emerging investigator article, which we've done more than half of the months since launching the feature in late 2017, we schedule a Twitter Journal Club with that author, where we participate, over the course of several hours, in pretty intensive conversation, about not only the science, but career development in Heart Failure Space, the importance of mentoring, and sponsorship obstacles that people are facing in development as physician scientists or scientists, and insights they may have into fostering success in the Heart Failure Space. This has been a great feature, we launched it because we feel that the emerging scientists, in the Heart Failure Space, need a virtual community in those critical years, before you have a lot of resources to start traveling, and setting up a network that's based on personal interaction, and we felt that, the modern era of social media was perfect for this. We found our emerging investigators are getting to know one another, they participate in one another's Journal Clubs, the Journal Clubs are incredibly fun, and interactive and we're getting a lot of Twitter engagement from the Heart Failure Community, there's a lot of "Twitteratti" in Heart Failure that really are engaged, and engaged with the Journal, which has really been fun for all of us, I think, so that's the thing we're most excited about. Dr Amit Khera:                  It's really wonderful to hear how you're spotlighting authors in creative ways. Tell us a bit about how your journal is advancing the mission of Heart Failure and Transplantation. Dr Nancy Sweitzer:          I see the journal as central to advancement of the subspecialty, as I mentioned earlier, Heart Failure is a relatively young subspecialty in the United States, we received a CGMC designation as a subspecialty just in 2008, just eleven years ago, and it's been a board certifiable subspecialty only since 2014. So, we're very young, and I think really developing into our own. We've seen tremendous growth in the number of people seeking subspecialty training in Advanced Heart Failure and Transplant Cardiology, and we are really enjoying helping the Journal evolve with the specialty, as it evolves, and that's happening very actively right now. So, I think what Heart Failure is in 2019 is different than what it was just five years ago in 2014. We're doing a lot more ,as I mentioned, Complex Chemo Dynamic Thinking, thinking about the path of physiology in our patients, and how we can target that effectively, not only with existing therapies, but with strategies, and, as I mentioned, the burgeoning growth of Mechanical Circulatory Support, and support devices, which the field has embraced quite actively, and The Journal is increasingly publishing content in these spaces, as well as the spaces of Advanced Heart Failure, but, I guess also, we're interested in every aspect of Heart Failure, from Complex Multidisciplinary Care Management, to Palliative Care, to the interaction of the heart with other organ systems, and Heart Failure such as the brain, we have a paper on Cognitive Function Abnormalities, and Heart Failure in this month's issue. So, the interaction with the brain, the kidney, the liver, many other organs, that are affected when the heart becomes quite ill with Advanced Heart Disease. So, basically we're interested in everything that touches Heart Failure Development Care, and treatment of patients with Heart Failure, and particularly we're interested in the newest and latest. We love publishing, and some of our highest impact papers in the last couple years have been new therapies, just being tested for the first time in patients with heart failure. Small studies that may not have large impact in terms of heart outcomes, but where we're learning about the pathophysiology of the disease, and new treatments, that's really exciting to us. We've published a couple of methods papers in the last year, really innovative models. One describing a model of pacing in mice, which has been a really challenging thing to do in Heart Failure, but several groups have now developed Tachycardia induced Cardiomyopathy models in mice, which is important for rapid discovery work, because mice have such a short reproductive span, and can be genetically altered, and then a recent publication on the methods paper, looking at a new initiative by the FDA, to potentially approve therapies based on patient reported outcomes, rather than just heart mortality and morbidity outcomes, so we're really excited about the innovations, and the Heart Failure Space, the work that describes where we're going as a field and as a profession. You'll see some features coming up in the journal, from opinion leaders across the globe on where this specialty sits in 2019, and where we, as the leaders in the field, can guide it as we move into our next decade, and I think that some of the most exciting work the journals doing. Dr Amit Khera:                  Thank you, Dr Sweitzer. We really appreciate your time today for the podcast, and your insights on the Journal. Dr Robert Gropler:          Good afternoon, I'm Rob Gropler. I'm the Editor-in-Chief of Circulation Cardiovascular Imaging. It's one of the journals within the family of Circulation Journals, and our focus is really on being the most influential source of leading edge imaging sciences, as it relates to transforming cardiovascular care, so what that means is, that we're interested in all imaging studies that are applied to the care of the cardiovascular patient, and although our primary focus is really on clinicians, and researchers, but we also want to expand our viewership, if you will, to anyone who is interested in how imaging is used to understand Cardiovascular Medicine, and to treat patients with Cardiovascular Disease. So, we are edged in all forms of imaging, this can be from MR, to echo, to nuclear, to CPT, to optical imaging, it involves all types of disease, ranging from Congenital Heart Disease, up to diseases in the elderly, it also involves not just it is in humans, but also understanding disease in the preclinical space, particularly as it helps us understand new technologies that may ultimately reach human use, either for investigational purposes, or ultimately, to be used in the treatment of a patient with Cardiovascular Disease. Dr Amit Khera:                  What are some innovative things you and the Journal are planning for this year? Dr Robert Gropler:          We're doing quite a few things. One of the first things we did, as you know, were relatively new, where we've only been an editorial team, if you will, for one year. One of the major efforts has been to increase our presence, in terms of digital media strategies, across the board. And so, this meant expand our Twitter presence, if you will. It also meant increasing our offerings in that digital space by, for example, having a journal club, what we would do is on a every other month basis, discuss a paper we published that's of significant interest via Twitter. And it would involve the authors, the associate editors who actually manage that study, as well as the editorialist who wrote about that study, and it leads to very unique insights into how that paper is being viewed by the scientific community at large, and also potentially how that information will be implemented in terms of transforming clinical care.                                                 We've added what we call a teaching file. If you think about imagers, imagers learn by seeing images. And the more they can see images, put them in the context of clinical cases, the more they understand what an image means when they see it. So, what we do now is we accept a large number of what we call imaging cases. These are specific unique cases that have a history, and then a short write up about them.                                                 And those are gathered each month, but then they're downloaded into a file. And then, anyone with access to the Journal can then look at, use to learn from, to potentially use for talks to enhance their own education the education of others. And we have found that to be, again, another offering that our readers particularly like. Dr Amit Khera:                  And how do you see Circulation Cardiovascular Imaging advancing the mission of imaging, which seems to be ever-expanding, and ever-growing? Dr Robert Gropler:          We're really in the education business. And what that means is that we're educating at a multi-scale level. Just educating a practitioner on what technology can do, how it's helping cardiovascular medicine, yes, that's important. But what we're also doing, is we're educating the scientists as to here as some of the new findings that were coming out because of imaging. And then that, in turn, will help direct them or signal them as to where is the science leading them, and what should be their next steps?                                                 We're also educating the general public as to what can imaging do, and how does imaging change cardiovascular medicine for the better, and what they can expect from that. And we're also educating the regulatory bodies, if you will, that determine what imaging can be done in the clinical environment and so on, and the importance of these imaging techniques.                                                 So number one, I think we always have to maintain that focus, as to that's our goal. Now, that being said, I think the question becomes how do you convey that concept? And where we have to continually evolve.                                                 And I think they were very smart years ago to make it a digital-only journal, as opposed to combined print and digital. So, I think that was actually very savvy. But the digital net component now has to expand. And that means our offerings have to reflect not just that people learn in different ways, that is, we have to have not just, if you will, a didactic or print equivalent component of a paper. But it also should be audio-based, such as this podcast. But they also need to be varied as in terms of the types of offerings, and their brevity or length, if you will. Dr Amit Khera:                  Thank you, Dr Robert Gropler, the Editor-in-Chief of Circulation Imaging. We really appreciate your time today. Dr Robert Gropler:          Thank you very much. You have a great day. Dr Amit Khera:                  Well, I'm sure you enjoyed this as I did. We really got incredible insight from the Editors-in-Chief of our Circulation family of journals. We learned so much about the broad array of subspecialties that they cover, and all the exciting and innovative things they're doing to really advance the missions of their fields, and also for the authors and for science.                                                 Well, again, I'm Amit Khera, associate editor from UT Southwestern, Digital Strategies editor for Circulation. And next week, you'll have your usual hosts, Carolyn Lam and Greg Hundley. Dr Carolyn Lam:                This program is copyright American Heart Association 2019.  

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                                 In our first article, Daniel Alyesh, Konstantinos Siontis and associates described myocardial calcifications in patients with ischemic cardiomyopathy undergoing ventricular tachycardia ablation in comparison to a control group of patients without ventricular tachycardia. They found that in 56 consecutive post-infarction patients, myocardial calcifications were identified in 39 or 70% of post-infarction ventricular tachycardia patients compared to 6 or 11% of patients without ventricular tachycardia. A calcification volume of 0.538 centimeters cube distinguished patients with calcification-associated ventricular tachycardia from patients without calcification-associated ventricular tachycardias; area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88. A non-confluent calcification pattern was associated with ventricular tachycardia target sites independent of calcification volume, P equals 0.01. Myocardial calcifications corresponding to areas of electrical non-excitability forming a border for re-entry were found in 33% of all ventricular tachycardias for which target sites were identified, and in 62% of patients with myocardial calcifications.                                                 In our next paper, Mia Fangel and associates examined whether glycemic status evaluated by hemoglobin A1c has an effect on the risk of thromboembolism among patients with atrial fibrillation and Type 2 diabetes. They used a cohort study from 5,386 patients with incident non-valvular atrial fibrillation and Type 2 diabetes in Danish registries. Compared with patients with hemoglobin A1c of less than or equal to 48 millimole per mole, they observed a higher risk of thromboembolism among patients with hemoglobin A1c 49 to 58 millimoles per mole with a hazard ratio of 1.49 and a hemoglobin A1c greater than 58 millimole per mole with a hazard ratio of 1.59 after adjusting for confounding factors. Surprisingly, in patients with diabetes duration of 10 years or more, higher hemoglobin A1c levels were not associated with a higher risk of thromboembolism.                                                 In our next paper, Niek Beurskens and associates compared tricuspid valve dysfunction in leadless pacemaker therapy to dual chamber transvenous pacing systems. They studied 53 patients receiving a leadless pacemaker, including 28 with a Nanostim and 25 with a Micra device. Of these 53 patients, 23 or 43% had tricuspid regurgitation that was graded as being more severe at 12 months. Compared with an apical position, a right ventricular septal position of the leadless pacemaker was associated with increased tricuspid valve incompetence, odds ratio, 5.20; P equals 0.03. An increase in mitral valve regurgitation was observed in 38% of patients. Leadless pacemaker implantation resulted in a reduction of right ventricular function. Leadless pacemaker implantation was further associated with a reduction in left ventricular ejection fraction and elevated LV TI index. The changes in tricuspid regurgitation in leadless pacing group was similar to the changes in dual-chamber transvenous pacemaker group, 43% versus 38% respectively; P equals 0.39.                                                 In our next paper, Jurgen Duchenne and associates examined whether regional left ventricular glucose metabolism correlates with regional work in an animal model with reversible dyssynchrony due to pacing. In 12 sheep, after 8 weeks of right atrial and right ventricular free wall pacing, there is evidence of left ventricular dilatation and thinning of the septum and thickening of the lateral wall. The authors employed motion compensation and anatomical correction in order to provide reliable regional estimates of myocardial glucose metabolism. They found that in homogenous regional distribution of myocardial workload due to left bundle branch block triggers adaptive remodeling of the left ventricle, leading to a more homogenous load distribution per volume unit myocardium. In reverse, cardiac resynchronization therapy leads acutely to an inhomogeneous distribution of workload, which homogenizes over time due to reverse remodeling. The authors concluded that redistribution of regional loading appears as a mode of action of cardiac resynchronization therapy so that myocardial mechanics should be the main treatment target of cardiac resynchronization therapy.                                                 In our next paper, Jihye Jang and associates examined the association between local conduction velocity and late gadolinium enhancement and myocardial thickness in a swine model of healed left ventricular infarction. They studied six swine with healed myocardial infarction and two controls. The authors found a significantly slower conduction was found in late gadolinium enhancement regions, 0.33 versus 0.54 meters per second, P less than 0.001, and regions of wall thinning, 0.38 versus 0.55 meters per second, P also less than 0.001; areas with greater late gadolinium enhancement heterogeneity and wall thickness gradient exhibited slower conduction velocity.                                                 In our next paper, Xi Zhang and Xiaohui Kuang and associates studied whether restricting contact force to less than 20 grams reduces the risk of esophageal injury in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. In a prospective, single-center, randomized study, 89 consecutive patients, mean age 57.2 years, 57% men, with atrial fibrillation, 68.5% paroxysmal and 31.5% persistent were randomized to restrictive contact force group or non-contact force group. The primary end point was a rate of esophageal injury post ablation. The same power setting, similar ablation time, and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus were present in both groups, there were no cases of esophageal injury in the restricted contact force group versus 9 or 20% of cases of esophageal injury post ablation in the non-contact force group. There are similar rates of freedom from atrial tachyarrhythmias at a mean of 31.3 months follow-up, 68.2% versus 64.4%.                                                 In our next paper, J. Martijn Bos and associates examined whether sodium channel blockers like mexiletine may have a potential role in LQT1 and LQT2, two forms of potassium channel mediated long QT syndrome. They retrospectively studied 12 patients, 5 females, median age at diagnosis 14.1 years with genetically established long QT2 in 10 or a combination of LQT1/LQT2 in 1 or LQT2/LQT3 in 1, who all received mexiletine. Prior to diagnosis, six patients were symptomatic and prior to initiation of mexiletine, four patients experienced one breakthrough cardiac event on beta blocker therapy. Median age at first mexiletine dose was 24.3 years. After mexiletine, the median QTc decreased by 65 milliseconds from 547 milliseconds pre-mexiletine to 470 milliseconds post-mexiletine, P equals 0.0005 for all patients. In eight patients or 67%, the QTc decreased by 40 milliseconds with a mean decrease in QTc of 91 milliseconds, P less than 0.008. For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.                                                 In our final paper, Andrea Mazzanti and associates assessed whether low dose quinidine in Brugada Syndrome patients reduces the occurrence of life-threatening arrhythmic events in this population. They compared the clinical course of 53 Brugada Syndrome patients treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and duration of observation. The 53 Brugada Syndrome patients, 89% males, median age 39.8 years, received quinidine at 439 milligrams per day for 5.0 years. Therapy was stopped in three cases or 6% for side effects. Quinidine reduced by 26% the risk of experiencing life-threatening arrhythmic events in cases versus controls; hazard ratio, 0.74; P equals 0.62. In 27 of 123 Brugada Syndrome patients symptomatic for life-threatening arrhythmic events who were treated for 7.0 years, the annual rate of life-threatening arrhythmic events decreased from 14.7% while off-quinidine to 3.9% while on-quinidine, P equals 0.03. The authors noted that recurrent life-threatening arrhythmic events were recorded in 4 or 15% of cardiac arrest survivors while on-quinidine, underscoring the importance of implantable defibrillator therapy.                                                 That's it for this month. We hope that you will find the Journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.  

Our lives unfold in space-time. It’s the water in which we swim and so like fish, it is difficult to know the influence of the matrix within which we live our days and experiences our lives. The Chinese ba zi, the eight characters, is a system based on the heavenly stems and branches that can help us to orient to the influences that shape us and can guide us in making sense of certain seasons of our lives. While often used as a kind of 算命, suan ming, fortune telling system. The Ba Zi can help us or our patients to better understand the arising and falling away of particular influences that can affect our health and wellbeing. Listen in to this conversation on how these eight characters of influence can help us to orient to the cycles of heaven and earth.   Head on over to the show notes page for more information about this episode and for links to the resources discussed in the interview.  

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.                                                 In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data.                                                 Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28.                                                 In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients.                                                 Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI.                                                 In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P

“La réalité financière de l’IA? 3% du budget investi dans l’ensemble des activités IT de Suisse." Jérôme Berthier, Empowerment Foundation Celles et ceux qui ont suivi Airccelerate en 2018 ont entendu - et même vu - que l’intelligence artificielle (IA) a occupé nos podcasts et nos journées, avec la participation à plusieurs événements autour du big data en Suisse. Armés de micros, de jetons et d’une borne d’arcade (!) nous avons interrogés des professionnels intéressés par l’IA afin de mieux cerner les besoins actuels et les solutions existantes. Dans ce 26e épisode, WarcoBrienza et JeremieWagner reçoivent plusieurs experts publiés dans la récente étude pAIrspective: Jérôme Berthier (Empowerment Foundation), Paul Wang (Advisory Board Member chez High-Tech Bridge, Mt-Pelerin et membre de la direction pour Icon.ngo), Sandro Saitta (Chief Industry Advisor chez Swiss Data Science Center) ainsi que l’instigateur du projet, Lionel Clavien (CTO d’InnoBoost). L’utilisation de l’Intelligence Artificielle devient réalité, même en Suisse. Les professionnels de la finance, de la production, du marketing, des ventes ou des RH sont ou seront impactés dans leur quotidien, à des degrés variables. Pas évident pour autant de comprendre comment l’IA nous impacte(ra) à nos places de travail. Fin 2018, 115 personnes actives en Suisse se sont prêtées au jeu du questionnaire pAIrspective, étude dont l’objectif est de publier l’”état des besoins” actuels et des solutions qui s’y prêtent déjà. Quatre experts en IA nous accompagnent pour cette émission très spéciale: Jérôme Berthier travaille comme vice-président de l'Empowerment Foundation; il a préalablement dirigé l’une des plus importantes société IT de Suisse, ainsi qu’un Innovation Lab; Paul Wang est advisor stratégique en matière de cybersécurité et de gestion des risques. Membre de l'advisory board de Mt-Pelerin (projet blockchain dans la création de la banque du futur, combinant crypto-économie et finance traditionnelle) et de High-Tech Bridge (société spécialisée dans la détection des failles cybersécurité utilisant l'intelligence artificielle), il est aussi membre de la direction de Icon.ngo ( organisation non gouvernementale qui fédère une communauté européenne travaillant sur la confiance dans le cyberespace); Sandro Saitta a 10 ans d’expérience dans l’application de la Data Science dans des industries telles que la finance, les télécommunications, la chimie, les voyages en ligne et la vente au détail. Il est actuellement Chief Industry Advisor au Swiss Data Science Center. Sandro est titulaire d’un doctorat en informatique de l’EPFL et a fondé la Swiss Association for Analytics pour promouvoir la Data Science en Suisse; Lionel Clavien est l’auteur d’une thèse sur les robots mobiles autonomes, l’initiateur du livre blanc “L’Intelligence Artificielle en Suisse et en 2019” ainsi que le CTO d’InnoBoost, dont le coeur de métier est l’intégration de “briques d’IA” dans les infrastructures IT de sociétés cherchant à valoriser les données qu’elles traitent. Retrouvez les notes complètes de l'émission, ainsi que tous nos podcasts sur www.airccelerate.com Photo by https://www.empowerment.foundation

Dr Paul Wang:                   Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.                                                 In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.                                                 Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.                                                 In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.                                                 Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.                                                 In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P > 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P > 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.                                                 In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.                                                 In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.                                                 In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.                                                 The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.                                                 In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.                                                 Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.                                                 In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.                                                 In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.                                                 In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.                                                 This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                 Koji Miyamoto and associates conducted the AD-Balloon Study, which investigates the ideal number of free cycles during second-generation cryoballoon pulmonary vein isolation. In a prospective, multicenter, randomized clinical trial, the authors compared in 110 patients the addition of a three minute freeze after pulmonary vein isolation had been achieved to pulmonary vein isolation alone. Delayed-enhancement magnetic resonance imaging was also performed one to two months after the pulmonary vein isolation to assess the ablation lesions. The freedom from atrial arrhythmias at one year was similar. Log rank test, P equals 0.78 in the two groups, 87.3% in the extra three-minute freeze group, and 89.1% in the pulmonary vein isolation group. There was no significant difference in the frequency of gaps on the pulmonary vein isolation lines in the delayed-enhancement magnetic resonance imaging. The authors conclude that an insurance freeze after achieving pulmonary vein isolation may be unnecessary and time consuming.                                                 In our next study, Robert Sheldon and associates examined the genetic basis of vasovagal syncope. They studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. Common genetic variants were genotype for 12 genes for vascular signaling, potassium channels, the serotonin 5-HT1A receptor, the serotonin transporter and catecholamine-O-methyltransferase or COMT. They found that in 9 of 12 variants, there was no significant association between genotype and phenotype. However, the serotonin 5-HT1A receptor, HTR1-A G alleles were associated with syncope in males but not in females. P equals 0.005. The men with serotonin 5-HT1 receptor C alleles had a 9% likelihood of syncope while Gg males had a 77% likelihood of syncope. The SL6A4 promoter L alleles were associated with decreased syncope in males but increase in females. P equals 0.059. The Ll males had a 25% syncope likelihood and Ss males had a 47% syncope likelihood. The COMT A alleles were associated with decreased syncope in males but increased in females. P equals 0.017. The Gg males had a 50% syncope likelihood and A males had a 15% syncope likelihood. The Gg females had 52% syncope likelihood and the Aa females had a 73% syncope likelihood. The authors concluded that there is a sex-dependent effect of alleles of serotonin signaling in vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.                                                 In the next study, Michael Barkagan and associates sought to examine whether the standard criteria for mitral line block with endocardial and epicardial activation mapping may not distinguish from slow conduction or conduction via epicardial bridging connections. In 56 patients, the authors creates a posterior mitral line using radiofrequency ablation. Mitral block determined by pacing with conduction block defined as trans-isthmus time of 100 milliseconds or greater in reversal of coronary sinus activation during pacing from the left atrial appendage was achieved in 51 out of 56 or 91% of patients. In 11 of 51 or 22% of patients, high-resolution activation mapping, using Rhythmia, of the endocardium and epicardium via the coronary sinus demonstrated residual endocardial in 27% or residual epicardial in 73% connections. Epicardial bridging connections were distant from the line, 2.4 plus or minus 1.6 centimeters, inserting laterally at the proximal-mid coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium in 7 of 11 patients. Mitral line block was achieved in 75% by targeting these insertion sites. The trans-isthmus time had limited predictive value for distinguishing block from pseudoblock. The authors concluded the connections are a frequent cause of complex circuits, and their insertion sites can be targeted for ablation.                                                 In our next paper, Santiago Rivera and associates examined the causes of QRS variability in Papillary muscle arrhythmias usually attributed to anisotropy. In 33 patients with papillary muscle arrhythmias prospectively undergoing cardiac resonance imaging, papillary muscle connections away from the papillary muscle base were identified. Arrhythmogenic papillary muscles, N equals 35, exhibited a higher number of papillary muscle connections, 72 versus 18, P equals 0.01. Patients with inconsistent QRS precordial transition and inconsistent QRS access exhibited a 100% prevalence of papillary muscle connections. Those with consistent precordial transition and consistent QRS access showed 40% and 26% prevalence of papillary muscle connections respectively. Inconsistent QRS precordial transition and inconsistent QRS access predicted the presence of papillary muscle connections with 59% or 28% sensitivity and 100% specificity respectively. Those papillary muscles exhibiting clinical recurrence after ablation presented a higher prevalence of papillary muscle connections, 91% versus 60%, P=0.04.                                                 In our next paper, Jason Coult and associates examined the quantitative measures of the electrocardiogram waveform during ventricular fibrillation to assess myocardial physiology and predict cardiac arrest outcomes. They collected five second ventricular fibrillation ECG segments with and without chest compressions prior to 2,755 defibrillation shocks from 1,151 out of hospital cardiac arrest patients. 24 individual measures and 3 combination measures were optimized to predict functionally intact survival using 460 training cases. Measures predicted functionally intact survival in 691 independent test cases with an area under the receiver operating curve (AUC) ranging from 0.56 to 0.75 without chest compressions and 0.53 to 0.75 with compressions, P less than 0.001. Of all measures evaluated, the support vector machine model ranked highest both without chest compressions, AUC equals 0.75, and with compressions, AUC equals 0.75. The authors concluded the waveform measures predict functionally intact survival when calculated during chest compressions, but prognostic performance is generally reduced compared to analysis without compressions. Support vector machine models exhibited similar performance with and without compressions while also achieving the highest area under the curve.                                                 In our last paper, Hailey Jansen, Martin Mackasey and associates examined the effective natriuretic peptides in the specific natriuretic peptide receptor NPR-C on angiotensin II-mediated atrial fibrillation. The authors examined wild-type and NPR-C knockout mice to investigate the effects of angiotensin II administered three milligrams per kilo per day for three weeks on atrial fibrillation susceptibility and atrial function. In wild-type mice, angiotensin II increased susceptibility to atrial fibrillation and associated with a prolonged P wave duration, increased atrial refractory period, and slowed atrial conduction. These effects were exacerbated in angiotensin II-treated NPR-C knockout mice. Angiotensin II prolonged action potential duration and reduced action potential upstroke velocity. Angiotensin II also increased fibrosis in the atria in wild-type mice while angiotensin II-treated NPR-C knockout mice exhibited substantially higher atrial fibrosis. Co-treating wild-type mice with angiotensin II and the NPR-C agonist cANF, those dependently reduced atrial fibrillation inducibility by preventing some of the angiotensin II-induced changes in atrial myocyte electrophysiology and preventing atrial fibrosis. The authors suggested that the NPR-C receptor may represent a new target for the prevention of angiotensin II-induced atrial fibrillation via protective effects on atrial, electrical and structural remodeling.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time! This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights for this month's issue.                                                 In our first paper, Pasquale Vergara and Associates develop a predictive risk score to assess the outcome of ventricular tachycardia ablation creating what they call the IVT score. The authors examined 16 demographics, clinical, and procedural related variables in 1,251 patients. They used a technique called survival tree analysis, which uses a recursive partitioning algorithm to find relationships among variables.                                                 They then compared the survival time and time to VT recurrence in groups derived from survival tree analysis using a log rank test. A random forest analysis was then run to extract a variable importance index and internally validate the survival tree models. They found that the left ventricular ejection fraction, ICD, or CRT device, previous ablation were the best predictors of ventricular tachycardia recurrence. While left ventricular ejection fraction, previous ablation, electrical storm was identified as best predictors of mortality.                                                 They identified a high-risk group in which 65% of patients survived and 52.1% were free from VT occurrence. A medium risk group in which 84% survived and 72% were free of VT, and a low risk group in which 97% of patients survived and 88% were free of VT recurrence.                                                 In our next paper, Alwin Zweerink and Associates examined the relationship between cure restoration and left ventricular dimension as predictors of outcomes after cardiac re-synchronization therapy. The present study evaluates the effect of normalization of the cure restoration to left ventricular dimension on the prediction of survival after CRT implantation. They study 250 heart failure patients with left ventricular ejection fraction less than or equal to 35% in cure restoration greater than or equal to 120 milliseconds, and they normalize the cure restoration based on the left ventricular dimension. The left ventricular and diastolic volumes obtained using cardiac magnetic resonance imaging.                                                 Before CRT implantation were used for cure restoration normalization. During a follow up period of 3.9 years, 79 patients or 32% reached the primary end point, which combined death, left ventricular assist device, or heart transplantation. Using univariable cox regression they found that although the unadjusted cure restoration was unrelated to CRT outcome, P=0.116, the normalized cure restoration was a strong predictor of survival. Hazard ratio 0.81 per 0.1 milliseconds per milliliter, P=0.008.                                                 Women demonstrated higher normalized cure restorations than men, 0.2 milliseconds per milliliter, versus 0.55 millisecond per milliliter, P=0.003, and showed better survival after CRT. Hazard ratio 0.52 with P=0.018.                                                 In our next study, Markus Linhart and Associates examined the impact of catheter ablation gaps on outcomes after first pulmonary vein isolation. Using delayed gadolinium enhancement cardiac magnetic resonance imaging three months after radio frequency ablation, they found that in 94 patients, 62% with paroxysmal atrial fibrillation, that there was a mean number of 5.4 gaps per patients. Atrial fibrillation recurrence within the first year of ablation was observed in 21 patients with paroxysmal AF, 36%, and 19 patients with persistent atrial fibrillation, 53%.                                                 In the unit variate analysis, CHA2DS2 -VASc score, afib type and relative gap length were predictors of recurrence. In multi-variant analysis, only relative gap length was significantly associated with recurrence. Hazard ratio 1.16 per each 10% of the gap.                                                 In our next paper, Antonius van Stipdonk, Iris ter Horst, Marielle Kloosterman, Alexander Maass, Kevin Vernooy and Associates examined the value of cueres area compared to that of cure restoration and morphology as predictors of clinical echocardiographical outcomes following cardiac resynchronization therapy. The authors found that in 1,492 cardiac resynchronization therapy patients during a mean follow up of 3.4 years, 32% of patients reached the combined prior endpoint of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation.                                                 The authors found that cure restoration identified patients that did not experience the primary endpoint better than QRS morphology in cure restoration area under the curve 0.61 versus 0.55 and 0.51, P value less than 0.001. They also found that QRS area identifies patients with echocardiograph remodeling in response to CRT better than the QRS morphology and duration, area under the curve 0.69 versus 0.58 and 0.58, P < 0.001. In addition, QRS area was the only independent electrocardiographic determine associated with the primary endpoint. Hazard ratio 0.50 QRS area retained its significant associative outcomes in both patients with and without left bundle branch block in cure restoration greater than 150 milliseconds.                                                 Our next paper is a research letter in which Brian Hansen, Ning Li and Associates report the first in-vivo use in a canine model of near infrared optical mapping. In-vivo optical action potential showed a sharp upstroke that corresponded with atrial activation at a neighboring electrode. Imaging during in-vivo atrial fibrillation episodes showed re-entrant activation around the sinoatrial region minimizing the effect of motion artifact in validation in structurally remodeled hearts would be the next steps for this promising technology.                                                 Also, in a research letter, James Hummel and Associates studied whether infrared thermography over a six-centimeter segment can be effectively used to guide atrial fibrillation ablation. Thermography continuously sampled 7,680 points over a full 360 degree and refreshed every second. Ablation was guided by 3D mapping and performed using a 3.5-millimeter irrigated tip. Power was reduced to 25-watts on the left atrial posterior wall and could be further reduced to 20-watts in areas where there was excessive esophageal temperature rise. Esophageal temperature cutoff for radio frequency power delivery was initially 46 degrees and progressively raised to 50 degrees throughout the study at the discretion of the operators.                                                 All patients underwent upper endoscopy on post-ablation day one to three by a gastroenterologist blinded to temperature data. Thirty-four patients were studied, 94% of patients had luminal esophageal temperatures above 40 degrees during ablation of the posterior wall. Thermal events with Tmex greater than 40 degrees occurred commonly averaging 6.5 seconds during a procedure. On average, 231 seconds of ablation were performed with Tmex greater than 40 degrees centigrade. However, the excursions above threshold cutoff Tmex greater than 50 degrees centigrade lasted only 1.5 seconds per patient. In total, 38% of patients, 13 out of 34 had at least one energy delivery discontinued for exceeding threshold. This occurred eight out of 17 times or 47% when the cutoff was 46 degrees centigrade and five out of 15, or 33% at 50 degrees centigrade.                                                 On endoscopy one patient, 3% had thermal injury related to malpositioning of the infrared thermal probe below the region of ablation. Another patient had three lesions spanning 16 centimeters likely related to mechanical trauma with probe placement. The authors concluded that esophageal injury does not seem to occur with esophageal temperatures less than 50 degrees centigrade using thermography.                                                 In a review paper in this issue, Bruce Lerman and Associates discussed adenosine as a potent but underutilized tool that is useful in clarifying in clinical diagnoses of arrhythmias. Adenosine mediates its electrophysiological effect through binding to the cell surface adenosine receptor A1R, a G-protein receptor. In the sinoatrial node, activation of IKADO by adenosine results in negative chronotrophy, a manifestation of its modern effects on membrane hyperpolarization and a decrease in the rate of phase four depolarization. Adenosine also mediates its cellular effects in atrial and AV nodal cells predominantly through activation of IKADO. In atrial myocytes, this results in a shortening of action potential duration in decrease in refractoriness. By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened. A mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cyclic AMP stimulated levels of L-type calcium current.                                                 Adenosine has a negative dromotropic effect on the AV node. The most potent effects of adenosine are expressed in N-cells. In these cells, as well as AN-cells, adenosine decreases excitability by reducing the plateau amplitude in abbreviating action potential duration. In addition, it reduces the rate of rise of the upstroke of N-cells. NH-cells are insensitive to adenosine. Adenosine terminates permanent form of junctional recipriatachycardia in the retrograde accessory pathway limb. The mechanism in which adenosine causes block in the retrograde decremental accessory pathway is thought to be by hyper-polarizing the pathways membrane potential. Adenosine has been helpful in illuminating differences in etiology of decremental conduction in three predominant antigrid decremental accessory pathways. Atrial ventricular pathways, atrial physicular pathways, and nodoventricular pathways.                                                 Adenosine can elicit dormant conduction defined as a restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are three discrete clinical scenarios in which adenosine reveals dormant conduction - after pulmonary vein isolation, after achieving bi-directional cavo-tricuspid isthmus block, and following successful ablation of antegrade and retrograde accessory potential. Adenosine, through activation of IKADO hyperpolarizing these cells so that the sodium channels are reactivated, restoring excitability. Adenosine, though its inhibition of cyclic ANP mediated increases in the slow inward calcium current and its downstream inhibitory effects on SR-calcium release, INCX and ITI, terminates focal arrhythmias caused by triggered activity. The response to adenosine may indicate triggered activity where termination occurs versus insensitivity of localized re-entry to adenosine.                                                 That's it for this month, we hope that you will find The Journal to be the go-to place for everyone interested in the field. See you next time.

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                                 In our first paper, Elizabeth Saarel and associates describe the analysis of athletes in the ICD sports registry. The authors found that over a median follow-up of 42 months of 129 young athletes, and a mean age of 16 years, there were 35 athletes, or 27%, that received a total of 38 shocks. Long QT syndrome and hypertrophic cardiomyopathy were the most common diagnoses. While shocks related to competition and practice were not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in an unselected pediatric ICD populations. There were no occurrences of death, arrest, injury related to arrhythmia during sports. There was one ventricular tachycardia ventricular fibrillation storm during competition.                                                 In our next paper, Kedar K. Aras and associates theorize that the tissue volume to wavelength volume ratio is important in determining ventricular fibrillation sustainability. They perform panoramic optical mapping of coronary perfused human left ventricular wedge preparations, which were subjected to acts of potential duration changes produced by IK,ATP agonist pinacidil and antagonist glybenclamide. They found that pinacidil and escalating concentrations progressively decreased the volume wavelength in ventricular fibrillation became sustained when the tissue volume to wavelength ratio was above the safety factor, K equals 4.4. In addition, ventricular fibrillation was only sustained when the ventricular volume exceeded the critical wavelength volume defined by the product of pacing cycle wave length in the longitudinal transverse and transmural directions.                                                 In our next paper Thomas Deneke and associates examine the ability of a novel infrared thermal probe to predict endoscopically detected thermal esophageal lesions post atrial fibrillation ablation. They studied six patients undergoing their first pulmonary vein isolation, using radio frequency point by point catheter ablation in the HEAT-AF study; 12 or 19% of patients had endoscopically detected thermal esophageal lesions. The peak esophageal temperature Tpeak was significantly higher, 56.3 degrees Celsius versus 45.7 degrees Celsius. P less than 0.0001 in patients with endoscopically detected thermal esophageal lesions compared to those without lesions. Logistical regression analysis demonstrated Tpeak was a statistically significant predictor, P equals 0.0008 pf endoscopically detected thermal esophageal lesions with an odds ratio of 1.52.                                                 In our next paper Dian Cheng and associates examine a novel algorithm incorporating right precordial and posterior leads to discriminate between left ventricular outflow tract and right ventricular outflow tract foci. The V3R to V7 index was prospectively tested in consecutive patients at four centers. In 94 patients of the validation cohort with 79% RVOT foci, a QS pattern in lead V3R exclusively recorded in right ventricular outflow tract foci, while an S wave in V3 was exclusively recorded in left ventricular outflow tract foci. The V3R to V7 index of LVOT origin was significantly great than that of RVOT 1.05 versus 0.28 P, less than 0.001 with a V3R to V7 index of greater than equal to 0.85 predicting an LVOT origin with 87% sensitivity and 96% specificity. With the V3R to V7 index of 0.85 or greater RVOT origin could be excluded with 98.6% accuracy.                                                 In the next paper Jim Cheung and associates examine the in-hospital outcomes, cause, and thirty-day readmissions following catheter ablation of MI associated ventricular tachycardia. The authors use a nationwide readmissions database to evaluate 4109 admissions for catheter ablation of MI associated ventricular tachycardia occurring between 2010 and 2015. The index admission in-hospital mortality rate was 2.7% and the procedural complication rate after ventricular tachycardiablation was 11.5%. Pulmonary hypertension, lung disease, obesity and coagulopathy were independent predictors of mortality. Following discharge after VT ablation the thirty-day readmission rate was 19.2%. With the median time to readmission of 10.0 days, in an in-hospital mortality of 2.9%. Cardiac causes accounted for 74% of readmissions. With ventricular tachycardia accounting for 41% of admissions and congestive heart failure accounting for 14% of readmissions. Pulmonary hypertension, congestive heart failure, smoking, chronic pulmonary disease, and prolonged index hospitalization were significant independent predictors of thirty-day readmission. After adjustment thirty-day readmissions were associated with a 38.9% increase in cumulative hospitalization costs.                                                 In the next paper Tomofumi Nakamura and associates examine the relation of hemorrhagic and thromboembolic events with anticoagulations strategy in the setting of epicardial axis procedures for ventricular arrhythmia mapping and ablation. In 355 patients oral anticoagulants were stopped perioperatively in heparin administered prior to the procedure. The patients were divided to three groups per the anticoagulations strategy. Group 1, no heparin was administered before pericardial access, Group 2, heparin was administered in reverse before pericardial access, and Group 3 heparin was administered and not reversed. Significant pericardial bleeding defined is greater than 80 milliliter occurred in 46 cases or 13% and did not differ among the three groups. Unintentional cardiac puncture in left ventricular chest infraction less than [inaudible 00:07:32] 35% were independently associated with pericardial bleeding with an odd ratio of 16.4 or 2.28. Of 38 procedures with unintentional cardiac puncture there were no differences in pericardial bleeding for different anti-coagulant strategies. Thromboembolic events occur in 5 patients, 1 coronary embolism, 1 stroke, 2 deep vein thrombosis, and 1 fatal pulmonary embolism and 1 thrombus on a temporary ventricular assist device.                                                 In the next paper, Elisabeth Mouws and associates examine whether the combination of lines of conduction block with multiple wave fronts at the pulmonary vein area may result in increased arrhythmogenicity and susceptibility to atrial fibrillation. The author performed intra-operative high-density epicardial mapping of pulmonary vein area and is 450 sites with an intra-electrical distance of 2 milliliters which performed during sinus rhythm in 327 patients. With and without preoperative intra-fibrillation. Excitation of the pulmonary vein area occurred via multiple consecutive wave fronts in the vast majority, 81% of patients. In total 561 wave fronts were observed which propagated through the septal or paraseptal regions tore the pulmonary vein area in 82%. Substantial dissociation of consecutive wave fronts was observed with delta activation times of 10.6 milliseconds. No difference was observed in delta activation times of consecutive wave fronts during sinus rhythm between patients with and without atrial fibrillation. In excitation-based risk factor model including conduction delay of greater equal to 6 millimeters conduction block of greater than or equal to 6 millimeters and conduction delay conduction block of 16 millimeters or greater, wave fronts vie the posterior inferior and posterior superior in multiple opposing wave fronts demonstrated a 5-fold risk of atrial fibrillation when multiple risk factors were present.                                                 In our final paper Yoshitaka Kimura and associates examine the prognostics significance of PR interval prolongation on adverse cardiac events. They studied 176 patients with repaired tetralogy of flow with a median age of 17.4 years then they evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events were ventricular arrhythmias, atrial arrhythmias, heart failure, hospitalization, complete AV block, and all cause death. First degree AV block was noted 25 patients or 14% during a median follow-up of 10 years there was a progressive prolongation of PR interval 2.0 milliseconds per year. Importantly there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular disfunction. In contrast, patients who underwent pulmonary valve replacement, N equal 23, significant shortening of PR interval was noted, 204 versus 176 milliseconds, P equals 0.007. Cox regression analysis showed that the first degree AV block was an independent risk factor for ventricular arrhythmias hazard ratio 5.479, in complete heart block, hazard ratio 27.67, and it had a tendency for heart failure hospitalization, hazard ratio 3.3. In addition PR interval prolongation greater than 2 millisecond per year was also a significant risk factor for ventricular arrhythmias regardless of the presence or absence of first degree AV block in enrollment.                                                 That's it for this month. We hope that you will find the journal to be the go to place for everyone interested in the field. See you next time.

Dr Paul Wang:   Welcome to the monthly podcast, On The Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first paper, Ruairidh Martin and associates used ultra-high-density mapping to access the ventricular tachycardia circuit dependent upon re-entry, with scar regions in 36 tachycardias in 31 patients. The author has found that 11 of the ventricular tachycardia circuits and isthmuses were single-loop, and 25 were double-loop. Three had two entrances, five had two exits, and fifteen had dead-end activation. Isthmuses were defined by barriers which included anatomical obstacles, lines of block, and slow conduction in 27 out of 36 isthmuses. The barrier to conduction in isthmus appeared to be partially functional in 75% of circuits. Isthmus voltage is often higher in ventricular tachycardia than in sinus or paced rhythms. The authors found that conduction velocity in the VT isthmus slowed at the isthmus entrances and exits when compared with mid-isthmus. The mean conduction velocity was 0.08 meters per second in entrance zones, 0.29 meters per second in isthmus regions, p < 0.0001, and 0.11 meters per second in exit regions. P = 0.002.                                 In our next paper Daniel Duprez and associates found that plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk of atrial fibrillation. In a stratified sample of the Multi-Ethnic Study of Atherosclerosis (MESA), initially age 45 to 84 years, the authors examined in 3,071 participants plasma Procollagen Type III N-Terminal Propeptide, also known as P3NP, which reflects collagen synthesis in degradation in Collagen Type I Carboxy-Terminal Telopeptide, also known as ICTP, which reflects collagen degradation at baseline. The authors aimed to determine if the levels of these biomarkers were associated with incident atrial fibrillation in participants initially free of overt cardiovascular disease. Incident atrial fibrillation in ten-year follow-up was based on a hospital ICD code for atrial fibrillation or atrial flutter, in or outpatient Medicare claims, or ECG ten years after baseline. The authors found that baseline levels of these markers were positively related, both p < 0.0001 to incident atrial fibrillation in a model adjusting for age, race, ethnicity, and sex. These findings were attenuated but remain statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function.                                 In our next paper, Ahmet Adiyaman and associates conducted a randomized controlled trial comparing the safety and efficacy of minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation versus percutaneous catheter ablation pulmonary vein isolation. In 52 patients with symptomatic paroxysmal or early persistent atrial fibrillation, paroxysmal atrial fibrillation was present in 74% of patients. The authors found that percutaneous pulmonary vein isolation with a 56% single procedure arrhythmia-free survival at two years was not inferior to minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation, which had a 29% arrhythmia freedom, p = 0.059. Procedure-related major adverse events occurred in 21% of patients undergoing minimally invasive thoracoscopic pulmonary vein isolation, compared to none undergoing percutaneous catheter ablation with p = 0.029.                                 In the next paper, Richard Ang and associates examined whether the glucagon-like peptide-1 receptor agonist exendin 4 has an effect on ventricular action potential duration in susceptibility to ventricular arrhythmia in the rat heart in vivo and ex vivo. Ventricular monophasic action potentials recorded in anesthetized rats in vivo in isolated profused rat hearts in sinus rhythm and/or ventricular pacing. In vivo systemic administration of exendin 4 increased heart rate and this effect was abolished by beta adrenoceptor blockade. Despite causing sympathetic activation, exendin 4 increased axon potential duration at 90% repolarization, APD90, during ventricular pacing by 7% and reversed the effect of beta adrenoceptor agonist Dobutamine on APD90. In isolated profused hearts, 3 nanomolar exendin 4 increased APD90 by 14% with no effect on heart rate. Exendin 4 also reduced ventricular arrhythmia inducibility in conditions of beta adrenoceptor stimulation with Isoproterenol. Exendin 4 effects on action potential duration in ventricular arrhythmia susceptibility were prevented in conditions of muscarinic receptor blockade or inhibition of nitric oxide synthase. The authors concluded that glucagon-like peptide-1 receptor activation effectively reverses the effects of beta adrenoceptor stimulation on cardiac ventricular excitability and reduces ventricular arrhythmic potential. The effect of glucagon-like peptide-1 receptor activation on the ventricular myocardium is indirect, mediated by acetylcholine and nitric oxide, and, therefore, might be explained by stimulation of cardiac parasympathetic neurons.                                 In our next paper, Michael Barkagan and associates examined the role of modulating baseline impedance on ablation lesion dimension. Radiofrequency ablation was performed using an irrigated catheter at a fixed power setting of 30 watts 20 seconds and a multi-step impedance load from 100 to 210Ω ex vivo in 20 swine hearts and in vivo in the right atrium and in thigh preparations. Ablation was performed using similar power settings at three baseline impedances: low, 90 to 130Ω; intermediate, 131 to 180Ω; and high, 181 to 224Ω. The relationship between baseline impedance, current, and lesion dimensions were examined. Baseline impedance had a strong negative correlation with current squared for all of these experimental models with R either -0.93 or -0.94. Lesion dimensions at similar power setting were directly related to current squared with R = 0.853 for width and R = 0.814 for depth. In thigh muscle lesion depth was greatest at low impedance, 8.2 millimeters, compared to 6.5 millimeters and intermediate impedance and 4.2 millimeters at high impedance, p < 0.0001. In right atrial lines, low baseline impedance resulted in wider lines, 7.2 millimeters, relative to intermediate 5.8 millimeters and high impedance, 4.7 millimeters, p < 0.0001.                                 In the next study, Virginie Dubes and David Benoist and associates examined the origin of ventricular arrhythmias in animal model of repair of tetralogy of Fallot. They studied six piglets undergoing tetralogy of Fallot repair-like surgery compared to five sham-operated piglets. Twenty-three weeks post-surgery, the authors found that right ventricular dysfunction was present, while left ventricular function was preserved in tetralogy of Fallot pigs. Optical mapping showed longer action potential duration on the tetralogy of Fallot left ventricular epicardial and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction but not the transverse direction in tetralogy of Fallot ventricles compared to sham. Elevated collagen content was found in left ventricular basal and apical sections from the tetralogy of Fallot pigs. The tetralogy of Fallot left ventricles had a lower threshold for arrhythmia induction using incremental pacing protocols.                                 In our next study, Meera Varshneya and associates sought to understand the individual roles of slow and rapid delayed rectifier potassium currents, IKS and IKR, and quantify how effectively each stabilize the actions potential, protecting cells against arrhythmias across multiple species. The authors compared ten mathematical models describing ventricular myocytes from human, rabbit, canine, and guinea pig. They examined variability within heterogeneous cell population, tested the susceptibility of cells to a pro-rhythmic behavior, and studied how IKS and IKR responded to changes in the action potential. They found, one, models of higher baseline IKS exhibited less cell-to-cell variability in action potential duration; two, models with higher baseline IKS were less susceptible to early afterdepolarizations induced by depolarizing perturbations; three, as action potential durations lengthened, IKS increases more profoundly than IKR, thereby providing negative feedback that resists excessive action potential duration prolongation; and four, the increase in IKS that occurs during β-Adrenergic stimulation is critical for protecting cardiac myocytes from early afterdepolarizations under these conditions. The authors concluded that slow, delayed rectifier current is uniformly protected across a variety of cell types, suggesting that IKS enhancement could be potentially anti-arrhythmic.                                 In our final paper, Piotr Podziemski and Stef Zeemering and associates performed a direct one-to-one comparison between phase and activation time mapping in high-density epicardial direct contact mapping files of human atrial fibrillation. The authors examined 38 unipolar electrum files of ten seconds duration recorded in 20 patients with atrial fibrillation using a 16 x 16 electrode array placed on the epicardial surface of the left atrial posterior wall or right atrial free wall. Using sinusoidal recomposition and Hilbert Transform, 138 phase singularities were detected, with 104 out of 138 phase singularities detected within on electro distance, 1.5 millimeters, from a line of conduction block between non-rotating wave fronts determined by activation mapping. Only 18 rotating wave fronts were detected out of 8,219 detected waves based on wave mapping. Fourteen out of these 18 cases were detected as phase singularities in phase mapping. Phase analysis of filter electrograms produced by simulated wave fronts separated by conduction block also identified phase singularities on the line of conduction block. The authors found that phase singularities identified by phase analysis of filter epicardial electrograms colocalized with conduction block lines identified by activation mapping. The authors concluded that detection of phase singularity using phase analysis has a low specificity for identifying rotating wave fronts using activation mapping of human atrial fibrillation.                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.

Dr Paul Wang:                   Welcome to the monthly podcast On The Beat, where Circulation: Arrhythmia and Electrophysiology. I'm Doctor Paul Wang, editor in chief, with some of the key highlights from this month's issue.                                                 In our first paper, Parikshit Sharma and associates reported on the use of permanent his bundle pacing to improve hemodynamics in 39 patients with right bundle branch block. His bundle pacing was successfully performed in 37, or 95 percent of the patients, and resulted in narrowing of the QRS complex from 158 milliseconds to 127 milliseconds. P = 0.0001. An increase in left ventricular ejection fraction from 31 percent to 39 percent. P = 0.004, an improvement in the New York Heart Association functional class from 2.8 to 2.0 P = 0.0001. This work suggests that his bundle pacing maybe helpful in right bundle branch block patients with left ventricular dysfunction.                                                 In our next paper, Philippe Debruyne and associates added to our understanding of using catheter ablation to modulate the autonomic nervous system in patients with neurally mediated syncope, signs of no dysfunction and functional AV block. Prior reports of autonomic modulation using catheter ablation have required extensive ablation in both atria. In this article, the authors report a significant 95% reduction in syncope at six months as a result of targeted ablation in the right atrium alone, focusing on partial ablation of the interior right ganglionated plexus. Ablation is quite limited, taking a mean of seven minutes and creating a mean surface area of 11 millimeters squared. This technique has promise as a possible treatment for avoiding a need of pacemaker implantation in some patients.                                                 In our next paper, Shankar Baskar and associates examined the characteristics and outcomes of pediatric patients receiving implantable cardioverter defibrillators and compared them to their adult counterparts. They examined ICD recipients in the NCDRICD registry from 2010 to 2016. There were 562,209 total ICD implants, including 3461 pediatric patients. Of the pediatric patients, 60 percent of implants were for primary prevention with non-ischemic cardiomyopathy being present in 60 percent of the patients, the most common underlying disease. Over time, there is an increasing trend of both primary and secondary prevention ICD implantations, P less than 0.05. Compared to adults, pediatric patients were likely to have structural heart disease, hypertrophic cardiomyopathy, ion channelopathy, and to receive a single chamber device. All P less than 0.001. There is no difference in in-hospital complications between the adult and the pediatric cohorts, 2.4 percent versus 2.6 percent. However, among pediatric patients, lower weight, Ebstein's anomaly, worse New York Heart Association class dual chamber and resynchronization defibrillator were associated with greater risk of complications. Although, re-intervention for generator replacement or upgrade was more common in adults, the time to re-intervention was shorter in the pediatric cohort.                                                 In our next paper, Ahmed Hussein and associates examine the effect of using ablation index guiding ablation in 40 patients with persistent HO fibrillation on the rate of pulmonary vein reconnection. Pulmonary vein reconnection was seen as a mandatory repeat electro-physiologic study in 22 percent of patients, effecting seven percent of pulmonary veins. Ablation on the intravenous cryna was required in 44 percent of patients to achieve durable pulmonary vein isolation. Atrial tachyarrhythmia occurrence was documented in eight to 20 percent of patients, only one of whom had pulmonary vein reconnection at repeat study. At 12 months, 30 out of 40, or 95 percent of patients, were in sinus rhythm, with four or 10 percent of patients having starting antiarrhythmic drugs. Higher body mass index and excessive alcohol consumption were the only significant factors associated with atrial tachyarrhythmia occurrence.                                                 In our next paper, Atsushi Hirayama and associates examined whether acute exasperation of chronic obstructive pulmonary disease increases the risk of repeated atrial fibrillation related health care utilization. They examine 944 patients who are hospitalized for acute exasperation of chronic obstructive pulmonary disease and had emergency department visit or hospitalization for atrial fibrillation during a 450 day period. Compared to the reference period, the rate of atrial fibrillation related emergency department visits or hospitalizations significantly increased in the first 90 days after acute exasperation of chronic obstructive pulmonary disease. 7.3 versus 14.1 per one hundred person months, resulting in a risk ratio of 1.93.                                                 In our next paper, Namsik Yoon and associates examined the mechanisms underlying the electrocardiographic and arrhythmic manifestation of experimental models of early repolarization syndrome and the ameliorative effects of radio-frequency ablation. The authors recorded axis potentials, bi-polar electrograms, and transmural pseudo electrocardiograms for coronary perfused canine left ventricular wedge preparations in 11 animals.                                                 The ITO agonist, NS5806, the calcium channel blocker Verapamil and acetylcholine were used to pharmacologically mimic the effects of genetic defects associated with early repolarization syndrome. The provocative agents induce prominent j waves in the ECG secondary to the accentuation of the action potential notch in the epicardium but not the endocardium. Bipolar recordings displayed low voltage fractionated potential in the epicardium due to temporal and spatial variability and appearance of the action potential dome conceal the phase two reentry develop when the axon potential dome was lost at some epicardial sites but not others. Appearing in the bipolar electrogram, is discrete high frequency spikes. Successful propagation of the concealed phase two reentered beat precipitated ventricular tachycardia or ventricular fibrillation. Radiofrequency ablation of epicardium destroyed the cell displaying abnormal repolarization and thus suppressed the j waves and the development of ventricular tachycardia and ventricular fibrillation in six out of six preparations.                                                 Stavros Stavrakis and associates described ten patients out of 843 patients, or 1.2 percent with AV nodal reentry tachycardia who required ablation of the basal inferolateral left atria, during stable antegrade slow, retrograde fast, AV nodal reentry tachycardia, a single late atrial extra stimulus was delivered at the inferolateral left atria, near the mitral annulus. All patients had failed ablation in the inferior triangle of Koch, and or roof of the coronary sinus. In all ten patients, a late atrial extra stimulus advanced the his bundle potential by at least ten milliseconds and reset the tachycardia. Ablation at that site, eliminates slow pathway conduction and terminated the tachycardia. Ablation was successful at the site of the latest atrial extra stimulus delivered 49 milliseconds after the onset of this his bundle potential. In their series, no recurrent tachycardia was noted at one year follow up.                                                 In our final paper, Justine Bhar-Amato and Malcolm Finlay and associates examine the hypothesis that increased cholinergic tone exerts its pro-rhythmic effects in Brugada Syndrome through increasing dispersion of transmural repolarization in patients with spontaneous and drug induced Brugada Syndrome. Using a recording array in the right ventricular outflow tract and a micro-catheter in the great cardiac vein to record intracardial and epicardial signals, the authors constructed S1S2 restitution curves from the right ventricular apex at baseline and after edrophonium challenge.                                                 The authors studied eight Brugada Syndrome patients and compared them to eight control patients with super ventricular tachycardia. Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times, mean difference 26 milliseconds. In contrast, Brugada Syndrome patients showed longer endocardial than epicardial activation times, mean difference -15 milliseconds. Brugada Syndrome patients significantly larger transmural gradient in their activation recovery intervals, mean intervals 20.5 versus 3.5 milliseconds, with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased the gradients in both controls to a mean of 16 milliseconds. In Brugada Syndrome, to 29.7 milliseconds. However, these changes were attributed to epicardial activation recovery, interval prolongation in control patients. In endocardial activation recovery interval prolongation in Brugada Syndrome patients. Dynamic changes in repolarization gradients were also observed across the right ventricular wall in Brugada Syndrome patients.                                                 That's it for this month. We hope that you'll find the journal to be the go to place for everyone interest in the field. See you next time.  

Paul Wang:         Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. In our first paper from the Finland Group Registry, Nordenswan and her colleagues have further defined the risk of sudden cardiac death in ventricular arrhythmias in patients with cardiac sarcoidosis. While it has been observed that there's a high risk of lethal arrhythmias in cardiac sarcoidosis patients with high grade AV block, the incidents in these patients with lone AV block, in the absence of known VT or left ventricular dysfunction, has not been described. From the patients with myocardial inflammatory diseases in their registry, the authors identified 143 cardiac sarcoidosis patients with high grade AV block. Of these patients, 90 had lone AV block. For these patients, the five-year composite incidence of sudden cardiac death or VT was 24%, in comparison with 54% in AV block with ventricular tachycardia or severe left ventricular dysfunction, and 24% with AV block in non-severe left ventricular dysfunction.                                 These findings support implementation of an implantable cardioverter defibrillator for cardiac sarcoidosis patients with lone AV block. A recent study by Gold and Colleagues suggests atrial ventricular optimization improves reverse remodeling in patients with significant intraventricular electrical delay. In this sub-study of the Smart AV Trial, 275 subjects were randomized to either electrogram-based AV optimization, smart delay, or nominal AV delay, 120 milliseconds. In this mostly male cohort, with a mean age of 65 years, and a left ventricular ejection fraction of 28% at follow up, at six months the benefit of AV optimization increased as intraventricular electrical delay prolonged, defined as the time between the peaks of the right and left ventricular electrograms. The longest cohort trial of intraventricular conduction delay had 4.26 times greater odds of remodeling response with AV optimization compared with nominal AV delay. This suggests that the left ventricular lead position in AV optimization might have a synergistic effect in reverse remodeling in cardiac resynchronization patients.                                 Concerns have long been raised that anorexia nervosa causes QT interval prolongation predisposing these individuals to life-threatening ventricular arrhythmias and sudden cardiac death. Fredrickson and Associates made progress in challenging this conclusion, demonstrating that despite a slightly increased incidence in borderline mean QTC, greater than 440 milliseconds, in 430 female anorexia nervosa patients, compared to 123 healthy controls from the Danish Civil Register, there was no difference in the risk of prolonged corrected QT interval greater than 460 milliseconds between the two groups.                                 However, during a 10-year follow up, anorexia nervosa patients had a slightly increased risk of ventricular tachycardiac, aborted cardiac arrest, and cardiac arrest compared to healthy controls. Incidence of 0.5% in the anorexia nervosa patients versus 0.07% in healthy controls. In addition, anorexia nervosa patients had a significantly increased risk of all-cause mortality with a hazard ratio of 11.2 over 10 years compared to population-based cohort, suggesting that anorexia nervosa increases the risk of medical complications, including cardiac complications, but these are not directly related to anorexia nervosa's effects on corrected QT interval.                                 In our next paper, Ahmed Karim Talib and Associates reported on the outcomes of endocardial ablation of drug-resistant ventricular fibrillation in Brugada syndrome. Endocardial mapping ablation was performed in 21 patients with one or more episodes of ventricular fibrillation. Endocardial mapping revealed low voltage fractionated endocardial electrograms in 19% of patients. All patients underwent ablation of ventricular fibrillation triggers, followed by endocardial substrate modification. Noninducibility of ventricular fibrillation and normalization of Brugada ECG was documented in 14, in three patients, respectively. During a mean follow up of 54 months, seven patients, or 33%, experienced ventricular fibrillation recurrences, presence of cruris notching in D1 was associated with the presence of low-voltage fractionated endocardial electrograms in ablation failure.                                 In our next paper, Jae Yeong Cho and Associates tried to elucidate the mechanism of sudden cardiac death in patients with heart failure with preserved ejection fraction using an ambulatory recording in a rat model. They showed that rats who had a clinical phenotype of heart failure with preserved ejection fraction had prolonged QT and QTC intervals and reduced heart rate variability compared to the controls. Importantly, the rats with heart failure and preserved ejection fraction had significantly higher rates of spontaneous ventricular arrhythmias, and about a third died suddenly with ventricular arrhythmia being the terminal rhythm.                                 In our next paper, Elad Anter and Colleagues used a novel mapping algorithm which integrated atrial activation mapping, vector analysis, and the physiologic constraints of atrial excitation to determine an atrial arrhythmias mechanism in circuitry. Ander's group initially applied this technique to historical controls and found that atrial tachycardias were diagnosed and their termination site predicted with 92.5% accuracy. When this algorithm was then applied prospectively to mapping of unknown atrial arrhythmias in 20 patients, this technique was able to identify macroreentrant, localized reentrant in focal tachycardias, even when standard mapping techniques had failed. This enhanced mapping capability allowed for significantly shorter ablation time when compared to historical controls, 3.2 +/- 1.7 minutes versus 17.3 +/- 6.6 minutes.                                 In our next paper Richard Walton and Colleagues explored the anatomical and electrical characteristics of the moderator band which provides a substrate for macroreentrant ventricular tachycardia. Ventricular wedge preparations with intact moderator bands were studied from humans in two cases and sheep in 15 cases. The moderator band structure was remarkably organized as two excitable yet uncoupled compartments of myocardium in [inaudible 00:07:45]. In humans, actual potential duration was significantly shorter in the moderator band than the right ventricular myocardium. S1, S2 moderator band pacing induced unidirectional propagation via the moderator band myocardium, permitting sustained macroreentrant ventricular tachycardia.                                 In sheep, the instance of ventricular tachycardia for right ventricular moderator band, or S1 right ventricular, and S2 moderator band pacing was 1.3%, 5.1%, and 10.3%, respectively. Severing the moderator band led to ventricular tachycardiac termination, confirming a primary arrhythmic role. Inducible preparations had shorter actual potential durations in the moderator band than right ventricle, whereas noninducible preparations showed no difference.                                 In our final paper, Witt and Associates studied the outcomes of 1421 patients who underwent ICD generator placement at Mayo Clinic, Minnesota and Beth Israel Deaconess Medical Center. During a mean follow up of 2.7 years appropriate ICD therapy occurred in 30.6% of the patients, predicted by low left ventricular ejection fraction and history of appropriate ICD therapy prior to generator replacement. On the other hand, 23.7% died prior to appropriate ICD therapy, predicted by old age, low left ventricular ejection fraction, diabetes mellitus, chronic lung disease, peripheral vascular disease, low hemoglobin level, and low glomerular filtration rate. The progressive increase in mortality after ICD generator change was observed in those who had aggregation of non-cardiac co-morbidities.                                 That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time.  

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper this month, Shaan Khurshid and associates determine the frequency of rhythm abnormalities in 502,627 adults in the UK Biobank, a national prospective cohort. They found that 2.35% had a baseline rhythm abnormality. The prevalence increased with age, with 4.84% of individuals aged 65 to 73 years having rhythm abnormalities. During over three million person- years of follow up, nearly 16,000 new rhythm abnormalities were detected. Atrial fibrillation was the most frequent with three per thousand person-years. Bradyarrhythmia with almost one per thousand person-years. Conduction system disease is about one per one thousand years. Supraventricular and ventricular arrhythmias, each about one half per one thousand person-years. Older age was associated with a hazard ratio of 2.35 for each 10 year increase. Male sex, hypertension, chronic kidney disease and heart failure were all associated with new rhythm abnormalities. In our next paper, Fabien Squara and associates evaluated a method of determining the septal or free wall positioning of pacemaker or ICD leads during fluoroscopy. They compared in 50 patients a classical approach using posterior anterior, right anterior oblique 30 degrees, and left anterior oblique 40 degrees fluoroscopic imaging’s to 50 patients undergoing an individualized left anterior oblique or LAO approach. This individualized LAO approach view provided a true view of the interventricular septum. This angle was defined by the degree of LAO that allowed the perfect superimposition of the RV apex, using the tip of the right ventricular lead, temporarily placed at the apex, and one of the superior vena cava, inferior vena cava access using a guide wire. Transthoracic echo was used to confirm position of the right ventricular lead. Septal, or free wall, right ventricular lead positioning was correctly identified in 96% of patients in the individualized group, versus 76% in the classical group. P equals 0.004. For septal lead positioning fluoroscopy had 100% sensitivity, and an 89.5 specificity in an individualized group, versus 91.4% sensitivity, and a 40% specificity in the classical group. In our next paper, Elsayed Soliman and associates examined the lifetime risk of atrial fibrillation based on race and socioeconomic status. In the atherosclerosis risk in communities, ARIC, cohort, of 15,343 participants without atrial fibrillation, patients were recruited in 1987 to 1989, when they were 45 to 64 years of age, and followed through 2014. The authors identify 2,760 atrial fibrillation cases during a mean follow up of 21 years. The authors found that the lifetime risk of atrial fibrillation in the ARIC cohort was approximately one in three among whites, and one in five among African Americans. And, the socioeconomic status was inversely associated with cumulative incidents of atrial fibrillation before the last decades of life. In our next paper, Jonathan Steinberg and associates sought to determine the impact of atrial fibrillation episode duration threshold on atrial fibrillation incidents and burden in pacemaker patients in a prospective registry. In 615 pacemaker patients was device detected atrial fibrillation over a mean follow up of 3.7 years, 599 had one or more atrial fibrillation episodes of 30 seconds duration, with a mean number of 22 episodes. At 12 months, freedom from atrial fibrillation ranged from 25.5% to 73.1%, based on a duration threshold from 30 seconds up to 24 hours. Of patients with a first episode of 30 seconds to two minutes, 35.8% were free from subsequent episodes greater than two minutes at 180 days. The mean atrial fibrillation burden of 0.2% for patients with first episodes between 30 seconds and 3.8 hours, was significantly less than the 9.5% burden for those with greater than 3.8 hours. The authors concluded that small differences in atrial fibrillation episode duration definition can significantly affect the perceived incidents of atrial fibrillation impact reported outcomes, including atrial fibrillation success. An initial atrial fibrillation episode of 30 seconds does not predict clinically meaningful atrial fibrillation burden. In the next paper, Hongwu Chen and Linsheng Shi and associates examined the distinct electrophysiologic features of bundle branch reentrant ventricular tachycardia in patients without structural heart disease. They described nine patients, mean age 29.6 years, with normal left ventricular function and bundle branch reentrant ventricular tachycardia, with a right bundle branch block pattern in one patient, and left bundle branch block patterns in nine patients. In all left bundle branch block pattern ventricular tachycardia, the mean ventricular tachycardia cycling was 329.3 milliseconds, and the median HV interval during tachycardia was longer than that of baseline, 78 versus 71 milliseconds. The H to right bundle interval during ventricular tachycardia was slightly shorter, however, the right bundle to ventricular interval was markedly longer than that during sinus rhythm, 50 versus 30 milliseconds. In six patients with three dimensional mapping of the left ventricle, a slow anterograde, or retrograde conduction over the left His-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje related ventricular tachycardias were also induced in five patients. Ablation was applied to the distal left bundle branch block in patients with baseline left bundle branch block, and in one narrow QRS patient with sustained Purkinje related ventricular tachycardia, while right bundle branch was targeted in other patients. During a mean follow up at 31.4 months, frequent premature ventricular contractions occurred in one patient, and new ventricular tachycardia developed in the other patient. In the next paper, Michel Haissaguerre and associates examined detailed mapping in 24 patients who survived idiopathic ventricular fibrillation. They used multi-electrode body surface recordings to identify the drivers maintaining ventricular fibrillation, and analyze electrograms in the driver regions, using endocardial and epicardial catheter mapping during sinus rhythm. Ventricular fibrillation occurred spontaneous in three patients, and was induced in 16, while VF was non-inducible in five. Ventricular fibrillation mapping demonstrated reentrant and focal activities, 87% and 13% respectively. The activities were dominant in one ventricle in nine patients, while they were biventricular in the others. During sinus rhythm, areas of abnormal electrograms were identified in 15 out of 24 patients, or 62.5%, revealing localized structural alterations, in the right ventricle in 11, the left ventricle in one, in both in three. They covered a limited surface, 13 centimeters squared, representing 5% of the total surface, and recorded predominantly on the epicardium. 76% of these areas were co-located with ventricular fibrillation drivers. In nine patients without structural alterations, the authors observed a high incidence of Purkinje triggers, seven out of nine, versus four out of 15. Catheter ablation resulted in arrhythmia-free outcomes in 15 out of 18 patients at a 17 month follow up. In our next paper, David Spar and associates describe the effectiveness, safety, and compliance of the wearable cardioverter defibrillator in the identification and treatment of life-threatening ventricular arrhythmias in all US pediatric patients who wore a wearable defibrillator from 2009 to 2016, ages less than 18 years. The 455 patients had a median age of 15 years, median duration of wearable cardioverter defibrillator use of 33 days, and median patient wear time of 20.6 hours per day. The study population was divided into two groups, 63 patients with an ICD problem, or 392 patients without an ICD problem. The wear time was greater than 20 hours in both groups. There were seven deaths, or 1.5%. All patients were not wearing the wearable cardioverter defibrillator at the time of death. Eight patients, 1.8%, received at least one wearable cardioverter defibrillator shock treatment. Of the six patients who had appropriate therapy, there were seven episodes of either polymorphic ventricular tachycardia, or ventricular fibrillation, with a total of 13 treatments delivered. All episodes were successfully converted, and the patient survived. In our next paper, Marc Lemoine and associates used human-induced pluripotential stem cell-derived cardiomyocytes to examine differences in repolarization reserve. The authors compared the contribution of IKs and IKr on action potential durations in human left ventricular tissue, and the human induced pluripotential stem cell derived cardiomyocytes, or IPS-derived engineered heart tissue. They found that the IPS-derived heart tissue showed spontaneous diastolic depolarization in action potential duration, which were sensitive to low concentrations of Ivabradine. IKr block by E-4031 prolonged action potential duration 90 with similar EC50 in both the IPS-derived heart tissue and the human left ventricular tissue. But a larger effect size in the IPS-derived heart tissue, 281 milliseconds versus 110 milliseconds, in the human left ventricular tissue. While IKr block alone evoked early after depolarizations, it triggered activity in 50% of the IPS-derived heart tissue. Slow pacing reduced extracellular potassium blocking of IKr, IKs and IK1 were necessary to induce early after depolarizations in human left ventricular tissue. In accordance with their clinical safety, Moxifloxacin and Verapamil did not induce EADs in IPS-derived heart tissue. In both IPS-derived heart tissue and human left ventricular tissue, IKs block by HMR 1556 prolonged action potential duration 90 slightly in the combined presence of E-4031 and isoprenaline. In our next paper, Elizabeth Saarel and associates sought to obtain contemporary digital ECG measurements in healthy children from North America to evaluate the effects of sex and race, and to compare the results to commonly published data sets, using 2400 digital ECGs, collected for children less than 18 years of age with normal electrocardiograms at 19 centers in the pediatric heart network. The authors found that the QTc in lead II was greater for females compared to males for age groups three years or older, for whites compared to African Americans, for ages 12 years or older. The R wave amplitude in V6 was greater for males compared to females for age groups 12 years and greater; for African Americans compared to white or other race categories for age groups three years or greater; and greater compared to commonly used public data set groups for ages 12 years and greater. In our next paper, Pyotr Platonov and associates examined T-wave morphology as a possible predictor of cardiac events in patients with type 2 long QT syndrome mutation carriers with normal QTc intervals. The authors compared 154 LQT2 mutation carriers with QTc less than 360 milliseconds in men, and less than 470 milliseconds in women, with 1007 unaffected family members. Flat, notched, or negative T-waves in leads II or V5 on baseline ECG were considered abnormal. Using Cox regression analysis, the associations between T-wave morphology, the presence in mutations in the poor region of KCNH2, and the risk of cardiac events defined that syncope aborted cardiac arrest, defibrillator therapy, or sudden cardiac arrests were assessed. The authors found that LQT2 female carriers with abnormal T-wave morphology had a threefold increased risk of cardiac events compared to LQT2 female carriers with normal T-waves, while this association was not seen in males. LQT2 males with poor location of mutations had a six-fold increased risk of cardiac events than non-poor location males, while no such association was found in females. In our last paper, Yaniv Bar-Cohen and associates describe a percutaneous pacemaker entirely implanted in the pericardium, using a sheath for sub-xiphoid access to the pericardial space, and a miniaturized camera with fiber optic illumination, the micro-pacemakers were successfully implanted in six pigs. All animals were studied during follow up, survived without symptoms. That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time!  

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. Dr Paul Wang:                   In our first paper, Farhad Pashakhanloo and associates examine the three-dimensional structure of the healed infarct and the ventricular tachycardia reentrant pathways in high-resolution models of infarcted porcine hearts. The authors used ex vivo late gadolinium enhancement in diffusion tensor MRI data of eight chronically infarcted porcine hearts at sub-millimeter resolution in a novel scar map thickness metric to reveal the heterogeneous organization of infarct. The authors use simulation to model ventricular tachycardia pathways. They found that a surviving sub-endocardial tissue later of varying thickness less than or equal to 2.2 millimeters surrounding the scar participated in the majority of ventricular tachycardias. The authors concluded that these analyses provided a better understanding of infarc-related ventricular tachycardia. Dr Paul Wang:                   In our next paper, Thomas Hadberg Lynge and associates studied the incidence of sudden cardiac death in a population of congenital heart disease in Denmark. Among 24.4 million person years over a nine-year period, there were 11,451 deaths that were examined. Of 809 cases of sudden cardiac death, 90, or 11% of the cases, were from congenital heart disease. Of these cases, 53, or 59% had the diagnosis of congenital heart disease prior to death. The incidence of sudden cardiac death was 9.6 times higher among patients with congenital heart disease compared to patients without congenital heart disease, p

Paul Wang:         Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first study, Filip Plesinger and associates examined whether a computerized analysis of the body surface 12-lead ECG can be used to measure the ventricular electrical activation delay as a predictor of heart failure or death following resynchronization therapy in a MADIT-CRT trial.                                 The authors found that left bundle branch block patients with baseline ventricular electrical activation delay less than 31.2 milliseconds had a 35% risk of MADIT-CRT endpoints, while patients with ventricular electrical activation delay greater than or equal to 31.2 milliseconds had a 14% risk, P value of less than 0.001.                                 The hazard ratio for predicting primary endpoints in patients with low ventricular electrical activation delay was 2.34 with a P value of less than 0.01. However, ventricular electrical activation delay was not predicted in patients with right bundle branch block or IVCD.                                 In our next study, Karl-Heinz Kuck and associates examined the predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation in 750 patients in the FIRE AND ICE Trial. Using propensity score stratification methods to count for differences in baseline characteristics between sexes, the authors found that female sex with a hazard ratio of 1.37, P equals 0.01, and prior direct current cardioversion with a hazard ratio of 1.40, P equals 0.013 were independently associated with atrial fibrillation recurrence.                                 Female sex with hazard ratio of 1.36, P value of 0.035 and hypertension with a hazard ratio of 1.48, P value of 0.013 independently predicted cardiovascular rehospitalization. A longer history of atrial fibrillation with a hazard ratio of 1.03, P value of 0.039 increased the rate of repeat ablation.                                 After propensity score adjustment, women continued to have higher rates of primary efficacy failure with adjusted hazard ratio of 1.51, P less than 0.05 and cardiovascular rehospitalization with a hazard ratio of 1.40, P less than 0.05.                                 In the next study, Laura Bear and associates examined the reliability of inverse electrocardiographic mapping of cardiac electrical activity from recorded body surface potentials. In five anesthetized closed-chest pigs, torso and ventricular epicardial potentials were recorded simultaneously during sinus rhythm, epicardial, and endocardial ventricular pacing. Two approaches, coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions, were compared.                                 The authors found that inverse mapping underestimated epicardial potentials more than twofold, P less than 0.0001. Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60 to 0.64 across all methods. Epicardial electrograms were recovered with reasonable fidelity at approximately 50% of the sites, but variation was substantial.                                 General activation spread was reproduced with a mean correlation coefficient of 0.72 to 0.78 for activation time maps with spatio-temporal smoothing. Epicardial foci were identified with a mean location error approximately 16 millimeters. Inverse mapping with method of fundamental solutions was better than coupled finite/boundary element methods.                                 The authors concluded that spatio-temporal variability of recovered electrograms may limit the resolution, with implications for accuracy of arrhythmia localization.                                 In the next study, Pejman Raeisi-Giglou and colleagues examined the incidence of pulmonary vein stenosis in 10,368 patients undergoing atrial fibrillation ablation from 2000 to 2015. Computed tomography scans were performed three to six months after the procedures. Severe pulmonary vein stenosis was observed in 52 patients, or 0.5%. The left superior pulmonary vein represented 51% of all severely stenosed veins.                                 Percutaneous interventions were performed in 43 patients, and complications occurred in five, including three pulmonary vein ruptures, one stroke and one phrenic injury. Over a median follow-up of 25 months, 41, or 79%, of patients remained arrhythmia-free.                                  In our next paper, Koichi Nagashima and associates compared hot balloon ablation and cryoballoon ablation in a 165 consecutive patients who underwent initial atrial fibrillation catheter ablation. Of the 165 patients, 74 propensity score-matched patients equally divided between hot balloon ablation and cryoballoon ablation were studied.                                 Patients' characteristics included age, sex, body mass index, atrial fibrillation subtype, CHA2DS2-VASc score, and left atrial dimension were similar between the two groups. 52% of the hot balloon ablation patients required touch-up with radiofrequency ablation for residual/dormant pulmonary vein conduction versus 24% of the cryoballoon ablation patients with a P value of 0.02.                                 The anterior aspect of the left superior pulmonary vein was the site in 41% of the touch-ups after hot balloon versus the inferior aspect of the inferior pulmonary veins in 22% of the touch-ups after cryoballoon ablation. Hot balloon lesions were smaller with an area of 23.8 centimeters squared compared to cryoballoon ablation lesions having an area of 33.5 centimeters squared with a P value of 0.0007. Within 12 months, both methods had an AF recurrence of 16%.                                 In our next paper, Mildred Opondo and associates randomized 61 patients, mean age 52 years, to either 10 months of high intensity exercise or yoga. The authors found that left atrial volume, Vo2 max, and left ventricular end-diastolic volume increased in the exercise group with no change in the control with a P value of less than 0.0001.                                 The authors did not find significant changes in atrial electrical activity and hypothesized that a longer duration training may be required to induce electrical changes.                                 In our next paper, because there's evidence that the distal part of the ligament of Marshall might be a sympathetic conduit between the left stellate ganglion and the ventricles, Shan Liu and associates randomly divided 29 dogs into a sham ablation group, a ligament of Marshall ablation group, and a left stellate ganglion ablation group. Ablation was performed before occlusion of the left anterior coronary artery.                                 Ligament of Marshall ablation attenuated blood pressure elevation induced by left stellate ganglion stimulation. Both ligament of Marshall ablation and left stellate ganglion ablation similarly prolonged ventricular refractory period and reduced the incidence of ventricular arrhythmias compared with sham ablation.                                 In our next study, Smith and Tester and associates examined the heterologous functional validation studies of putative long-QT syndrome subtype 2, LQT2, associated variants. Genetic testing of 292 sudden infant death syndrome cases identified nine KCNH2 variants, while some of the channels associated the variants can lead to accelerated deactivation and activation gating. Other current levels were similar to wild-type.                                 The authors examined the electronic health records of patients who were genotype positive for these particular sudden infant death syndrome–linked KCNH2 variants and found all of them had a median heart rate–corrected QT intervals less than 480 milliseconds and none had been diagnosed with long-QT syndrome or suffered cardiac arrest.                                 Simulating the impact of dysfunctional gating variants using computational models of the human ventricular action potential predicted that they have little impact on action potential duration. The authors concluded that these rare Kv11.1 missense variants are not long-QT2 causative variants and, therefore, do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.                                 In our next study, Tina Baykaner and associates performed a systematic literature review and meta-analysis to determine outcomes from ablation of atrial fibrillation drivers in addition to pulmonary vein isolation or as a stand-alone procedure. The authors found 17 studies with a cohort size of 3,294 patients.                                 Atrial fibrillation driver ablation, when added to a pulmonary vein ablation or a stand-alone procedure compared the controls, produced an odds ratio of 3.1 with a P value of 0.02 for freedom from atrial fibrillation and an odds ratio of 1.8 with a P value of less 0.01 for freedom of all arrhythmias in four controlled studies.                                 Adding atrial fibrillation driver ablation to pulmonary vein ablation resulted in a freedom from atrial fibrillation of 72.5%, P value of less than 0.01 and a freedom from all arrhythmias of 57.8% with a P value less than 0.01. Atrial fibrillation termination was 40.5% and predicted favorable outcome from ablation with a P value of less than 0.05. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to a pulmonary vein isolation.                                 In our next study, Hidekazu Kondo and associates found that the adverse atrial remodeling, including atrial inflammation, lipidosis and fibrosis, were induced in both wild-type and Interleukin-10 knockout mice by high fat diet, but the effects were exaggerated in the Interleukin-10 knockout mice. Vulnerability to atrial fibrillation was also significantly enhanced by the high fat diet.                                 The total amount of epicardial and pericardial adipose tissue volume was increased with high fat diet. Proinflammatory and profibrotic cytokines of epicardial and pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by the high fat diet. Systemic Interleukin-10 administration markedly ameliorated the high fat diet induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation.                                 The authors concluded that Interleukin-10 treatment may limit the progression of atrial fibrillation occurring in the setting of a high fat diet.                                 In our next paper, Garcia and Campbell and associates demonstrated the ability to deliver amiodarone epicardially over a sustained period of time. The authors demonstrated in a pig model of atrial fibrillation that an amiodarone containing polyethylene glycol-based hydrogel placed directly on the atrial myocardium in a minimally invasive catheter procedure significantly reduced the duration of sustained atrial fibrillation at 21 and 28 days. The authors found that inducibility of atrial fibrillation was also reduced.                                 In our final paper, Htet Khine and associates examined the effect of spaceflight on the changes in atrial structure, supraventricular beats, and atrial electrophysiology, and to determine whether spaceflight could increase the risk of atrial fibrillation.                                 The authors found that, in 13 that in astronauts, the left atrial volume transiently increased after six months in space without changing atrial function. Right atrial size remained unchanged, while one astronaut had a very large increase in supraventricular ectopic beats, none developed atrial fibrillation. The P-wave amplitude duration did not change over time, but RMS 20 decreased on all fight days except landing day.                                 That's it for this month. Thanks for listening to On the Beat. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next month.  

Dr. Paul Wang:           Welcome to the monthly podcast On the Beat for Circulation Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights for this month's issue. We'll also hear from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                                 In our first article, Barry Maron associates report on the long term clinical course of hypertrophic cardiomyopathy patients following ICD therapy for ventricular arrhythmias. They studied a cohort of 486 high-risk hypertrophic cardiomyopathy patients with ICDs from eight international centers. Of these 486 patients over 6.4 years, 94 patients or 19% experienced appropriate ICD interventions, terminating VT or VF. Of the 94 patients receiving appropriate ICD therapy, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions. Of these 87 patients, 74 or 85% remained in classes one or two without significant change in clinical status of the subsequent 5.9 years up to 22 years. Among the 94 patients, there was one sudden death in three patients who died from non arrhythmic hypertrophic cardiomyopathy related processes. Post ICD intervention, freedom from hypertrophic cardiomyopathy, mortality was 100% at one year, 97% at five years, and 92% at 10 years, distinctly lower than the risk of ischemic or non ischemic cardiomyopathy in ICD trials.                                                 Hypertrophic cardiomyopathy patients with ICDs interventions reported the heightened anxiety and expectation of future shocks. However, they did not affect general psychological well-being or quality of life. The authors concluded that in hypertrophic cardiomyopathy, unlike ischemic heart disease, prevention of sudden death with ICD therapies unassociated with a significant increase in cardiovascular morbidity and mortality, nor transformation into heart failure deterioration, ICD therapy does not substantially impair overall psychological and physical well-being. In our next article, Abdulla Damluji and associates examined the cost of hospitalizations for cardiac arrest using the US nationwide inpatient sample from 2003 to 2012. Using the log transformation of inflation adjusted costs the authors examined 1,387,396 patients who were hospitalized after cardiac arrest. They had a mean age of 66 years. Inpatient procedures included coronary angiography in 15%, PCI in 7%, intra-aortic balloon pump in 4.4%, therapeutic hypothermia in 1.1%, and mechanical circulatory support in 0.1% of patients.                                                 Notably the rates of therapeutic hypothermia increased from 0 in 2003 to 2.7 in 2012, p less than 0.001. Both hospital charges inflation adjusted costs linear increased over time. In a multi-variant analysis predictors of inflation adjusted costs included large hospitals size, urban teaching hospital, and length of stay. Among co-morbidities, atrial fibrillation or fluid and electrolytes imbalance were the most common associated with cost. The authors found that during the period between 2003 and 2012 post cardiac arrest, hospitalizations had a steady rise and associated healthcare costs likely related to increase length of stay, medical procedures and systems of care.                                                 In our next paper, Peter Huntjens and associates examined intrinsic interventricular dyssynchrony as a predictor of human dynamic response to cardiac resynchronization. The authors use a cardiovascular computational model CircAdapt to characterize the isolated effect of intrinsic interventricular or intraventricular activation on resynchronization therapy response that is the change in LV dP/dt max. The simulated change in LV dP to dt max had a range of 1.3 to 26.5% increased considerably with increasing inter ventricular dyssynchrony. In contrast, the isolated effect of intra ventricular dyssynchrony was limited with the change in the LV dP/dt max range and the left ventricle from 12.3 to 18.3% in the right ventricle from 14 to 15.7%.                                                 Secondly, electrocardiographic imaging derived activation characteristics of 51 CRT candidates were used to create individual models of ventricular activation in CircAdapt. The model predicted change in LV dP/dt max was close to the actual value in left bundle branch block patients with 2.7% difference between measured and simulated when only intrinsic interventricular dyssynchrony was personalized. Among non left bundle branch block patients a change in LV dP/dt max was systematically over predicted by CircAdapt with a 9.2% difference between measured and simulated. Adding intra ventricular activation to the model did not improve the accuracy of response prediction. The authors found that computer revealed intrinsic interventricular dyssynchrony is the dominant component of the electrical substrate driving the response to CRT.                                                 In the next paper Kenji Kuroki and associates examined the use of voltage limit adjustment of substrate mapping and fast Fourier transform analysis of local ventricular bipolar electrograms during sinus rhythm to predict VT isthmuses. They performed these studies and nine post infarction patients who underwent catheter ablation for total of 13 monomorphic ventricular tachycardias. Relatively higher voltage areas on electroanatomical map or defined as high voltage channels, which were further classified as full or partial if the entire or more than 30% of the high voltage channel was detectable. 12 full high voltage channels were identified in seven of nine patients. Relatively higher fast Fourier transform areas were defined as high frequency channels, which were located on seven of 12 full high voltage channels. Five VT isthmuses or 71% were included in the seven full high voltage channels positive in high frequency channel positive sites.                                                 While no VT isthmuses were found in five full high voltage channel positive but high frequency channel negative sites, high frequency channels were identical to 9 out of 16 partial high voltage channels. Eight VT isthmuses or 89% were included in nine partial high voltage channel positive in high frequency channel positive sites, whereas no VTs isthmuses were found in the seven partial high voltage channel positive and high frequency channel negative sites.                                                 All high voltage channel positive in high-frequency channel positive sites predicted VT isthmus with a sensitivity of 100% and specificity of 80%. The authors concluded that based on this small series that combined use of voltage, limited adjustment and fast Fourier transform analysis may be useful method to detect VT isthmuses.                                                 In the next study, John Whitaker and associates examined the use of lesion index, LSI index, a proprietary algorithm combining contact force, radio-frequency application duration, and RF current. Cardiac CT was used to assess atrial tissue thickness. Ablation lines two to three per animal were created in the right atrium in seven mini pigs with point lesions using 25 watts of energy. Two weeks after the ablation, serial sections of targeted atrial tissue or examine histologically to identify gaps and transmural ablation. LSI guidelines had a lower incidence of histological gaps. Four gaps in the 69 catheter moved or 5.8% compared to ablation using LSI plus two millimeter lines in which there is seven gaps in 33 catheter moves or 21.2% and using LSI plus four millimeter lines in which there are 15 gaps in 23 moves or 65.2% p less than 0.0. The change in LSI was calculated retrospectively is a distance between two adjacent lesions above the mean LSI of the two lesions. Changing LSI values of 1.5 or less were associated with no gaps in transmural ablation.                                                 The authors concluded that in this mod of chronic atrial ablation delivery of uninterrupted transmural linear lesions may be facilitated using LSI to guide catheter movement. When change in LSI between adjacent legions is 1.5 millimeters or lower, no gaps in atrial linear lesions should be expected.                                                 In our next paper, Matthew Bennett and associate examined whether their response to antitachycardia pacing in patients with ICD could further discriminate ventricular from super ventricular arrhythmias in patients receiving ATP in the RAFT trial. The RAFT trial randomized 1,798 patients with New York Heart Association class two or three heart failure, left ventricular ejection fraction less than or equal to 30%, in QRS duration 120 millisecond or greater, to an ICD plus or a minus cardiac resynchronization. Beginning with 10,916 ATP attempts for 8,150 tachycardia episodes in 924 patients, the author's excluded tachycardias where ATP terminated the episode or were the specific etiology tachycardia was uncertain. In this study, they analyzed 3,676 ATP attempts delivered to 2,046 tachycardia episodes in 541 patients. The authors found that a shorter difference between the post pacing interval is PPI minus TCL, was more likely to be associated with VT than SVT, mean of 138.1 milliseconds for VT and 277.4 milliseconds for SVT p, less than 0.001. A PPI minus TCL value of less than or equal to 300 milliseconds had a sensitivity in 97.4% and a specificity of 28.3% for VT.                                                 The authors concluded that specifically the PPI minus TCL following antitachycardia pacing may help distinguish ventricular from supraventricular arrhythmias.                                                 In the next study, Shailee Shah and Amr Barakat and associates examined the outcomes after repeat AF ablation. The authors examined 137 patients out of a total of 10,378 patients undergoing Afib ablation who had had initial long-term success defined from recurrent arrhythmias for greater than 36 months off anti-arrhythmic drugs in subsequent underwent repeat ablation for recurrent atrial fibrillation. The median arrhythmia free period that define long-term success was 52 months. In redo-ablations reconnection of at least one of the pulmonary veins was found in 111 or 81% of patients. Additional non PV ablations were performed in 127 or 92.7% of patients. After a mean follow-up of 17 months, 103 patients or 75% were arrhythmia-free, 79 off anti-arrhythmics, and 24 on arrhythmics. The authors found that repeat ablations with re-isolation to the point of veins and modifying the atrial substrate had a good success rate.                                                 In the next article Qiongling Wang and associates hypothesized that genetic inhibition of CaMKII oxidation in a mouse model of Duchenne muscular dystrophy can alleviate abnormal calcium homeostasis thus preventing ventricular arrhythmias. The authors tested whether the selective loss of oxidation of the CaMKII effects ventricular arrhythmias in the mouse model of Duchenne muscular dystrophy. Genetic inhibition of ox-CaM kinase II by knocking replacement of the regulatory domain methionines with valines, which we'll call MMVV, prevented ventricular tachycardia in the mdx mice. Confocal calcium imaging of ventricular myocytes, isolated from the mdx MMVV mice revealed normalization of intra-calcium release events compared to myocytes from the mdx mice. Abnormal action potentials as assessed by optical mapping mdx were also alleviated by genetic inhibition of ox-CaMK II. Knockout of the NADPH oxidase regulatory sub-unit P 47 Fox normalized elevated ox-CaMK II, repaired intracellular calcium hemostasis and rescued inducible ventricular arrhythmias in the mdx mice. The authors concluded that inhibition of ROS or ox-CaMK II protects against pro-arrhythmic intracellular calcium handling, preventing ventricular arrhythmias in a mouse model of Duchenne muscular dystrophy.                                                 In the next article, Kyohei Marume and Teruo Noguchi and associates examined whether the combination of QRS duration of 120 milliseconds or greater in late gadolinium enhancement is a precise prognostic indicator for the primary endpoint of all cause death and a composite of sudden cardiac death or aborted sudden cardiac death in 531 patients with dilated cardiomyopathy. They also analyzed the association between the combination of late gadolinium enhancement and increased QRS duration in these end points among patients with a class one indication for implantable defibrillator. The author's divided study patients in three groups according to late gadolinium enhancement in QRS duration. Two negative indices that is late gadolinium enhancement negative and narrow QRS, one positive index with either late gadolinium enhancement positive or wide QRS or two positive indices late gadolinium positive and wide QRS and followed them for 3.8 years. Multiple variable Cox regression analysis identified to positive indices as significant predictors of all cause death. A hazard ratio of 4.29 p equals 0.026. Among the 317 patients with a class one indication for ICD, the five year event rate of sudden cardiac death or aborted sudden cardiac death was lowest in the two negative indices groups, 1.4%. With propensity score matching cohorts the two negative indices group had a significant lower event rate of sudden cardiac death or aborted sudden cardiac death than to two other groups hazard ratio 0.2, p equals 0.046.                                                 The authors concluded that the combination of late gadolinium enhancement in wide QRS provides additional prognostic stratification compared to late gadolinium enhancement status alone.                                                 In the next study, Matthew Sulkin and associates examined whether a novel local impedance measurement on an ablation catheter identifies catheter tissue coupling and is predictive of lesion formation. The author's first studied explanted hearts, 10 swine, and then in vivo 10 swine, using an investigational electro anatomical mapping system that measures impedance from an ablation catheter with mini electrodes incorporated into the distal electrode. Rhythmia and Intellanav, Boston Scientific.                                                 Explanted tissue was placed in a warmed 37 degree celsius saline bath mounted on a scale, and the local impedance was measured 15 millimeters away from the tissue to five millimeters of catheter tissue compression at multiple catheter angles. Lesions were created for 31 and 50 watts from 5 to 45 seconds for an N of 70. During in vivo valuation of the local impedance measurements of the myocardium 90 and blood pool 30 were guided by intracardiac ultrasound while operators were blinded to the local impedance data. Lesions were created with 31 and 50 watts for 45 seconds in the ventricle with an n of 72. The local impedance of myocardium, which was 119.7 ohms, was significantly greater than in blood pool 67.6 ohms the p of less than 0.01. Models that incorporate local impedance drop to predict lesion size had better performance that models incorporate force time integral r squared of 0.75 versus r squared of 0.54 and generator impedance drop r squared of 0.2 versus r squared of 0.58. Steam pops displayed a significantly higher starting local impedance and a larger change in local impedance compared to successful RF applications, p less than 0.01.                                                 The authors concluded that local impedance recorded for miniature electrodes provides a valuable measure of catheter tissue coupling and the change in local impedance is predictive of lesion formation during RF ablation.                                                 In the next paper, Boaz Avitall and associates found that the rising impedance recorded from a ring electrode placed two millimeters from the cryoballoon signifies ice formation covering the balloon surface and indicates ice expansion. The authors studied 12 canines in a total of 57 pulmonary veins, which were targeted for isolation. Two cryoapplications were delivered per vein with a minimum of 90 and a maximum 180 second duration. Cryoapplications was terminated upon reaching a 500 ohm change from baseline. Animals recovered 38 plus or minus six days post procedure, and the veins were assessed electrically for isolation. Heart tissue was histological examined. Extra cardiac structures were examined for damage. Pulmonary vein isolation was achieved in 100% of veins if the impedance reached 500 ohms in 90 to 180 seconds. When the final impedance was between 200 and 500 ohms within 180 seconds of freeze time, pulmonary vein isolation was achieved in 86.8%. For impedance of less than 200 ohms pulmonary vein isolation was achieved in 14%. No extra cardiac damage was recorded. The authors found that impedance rise of 500 ohms at less than 90 seconds with a freeze time of 90 seconds resulted in 100% pulmonary vein isolation.                                                 In our final papers Sally-Ann Clur and associates examined left ventricular isovolumetric relaxation time as the potential diagnostic marker for fetal Long QT Syndrome. Left ventricular isovolumetric contraction time, ejection time, left ventricular isovolumetric relaxation time, cycle length, and fetal heart rate were measured using pulse doppler wave forms in fetuses. Time intervals were expressed as percentage of cycle length, and the left ventricular myocardium performance index was calculated. Single measurements were stratified and compared between Long QT Syndrome fetuses and controls. Receiver operator curves were reformed for fetal heart rate in normalized left ventricular isovolumetric relaxation time. A linear mixed effect model including multiple measurements was used to analyze fetal heart rate, the left ventricular iso volume metric relaxation time, and the left ventricular myocardial performance index. There were 33 Long QT fetuses in 469 controls. In Long QT fetuses the left ventricular isovolumetric relaxation time was prolonged in all groups, p less than 0.001, as was the left ventricular isovolumetric relaxation time.                                                 The best cutoff to diagnose Long QT syndrome was the normalized left ventricular isovolumetric relaxation time greater than equal to 11.3 at less than or equal to 20 weeks, giving a sensitivity in 92% and a specificity of 70%. Simultaneous analysis of the normalized left ventricular isovolumetric relaxation time and fetal heart rate improved the sensitivity and specificity of Long QT Syndrome, AUC of 0.96. The normalized left ventricular isovolumetric relaxation time, the left ventricular myocardial performance index, and fetal heart rate trends differed significantly between Long QT Syndrome fetuses and controls throughout gestation.                                                 The authors concluded that left ventricular volumetric relaxation time is Prolonged QT fetuses. Findings of a prolonged normalize left ventricular isovolumetric relaxation time, and sinus bradycardia can improve the prenatal detection of fetal Long QT Syndrome.                                                 That's it for this month, but keep listening. Suraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcasts On the Beat. Take it away Suraj. Suraj Kapa:                          Thank you, Paul and welcome back to On the Beat were we will be summarizing hard-hitting articles across the entire electrophysiologic literature. Today we'll be starting within the realm of atrial fibrillation where we're review an article within the realm of anticoagulation and stroke prevention. Quon et al. published in last month's issue of JACC cardiac electrophysiology on anticoagulant use and risk of ischemic stroke and bleeding in patients with secondary atrial fibrillation. It is well known that use of anticoagulation in atrial fibrillation can reduce overall thromboembolic outcomes. However, its role in secondary atrial fibrillation is unclear. Thus, the authors sought to evaluate the effects anticoagulant use on stroke and bleeding risk. Amongst those where atrial fibrillation occurred in the setting of acute coronary syndrome, pulmonary disease, or sepsis. Amongst around 2300 patients evaluated retrospectively there was no evidence of a lower incidence of ischemic stroke among those treated with anticoagulants compared to those who are not.                                                 However, anticoagulation was associated with a higher risk of bleeding in those with new onset AF associated with acute pulmonary disease. The authors suggest as a result that there is unclear overall benefit for long-term anticoagulation in patients with presumed secondary atrial fibrillation. The difficulty in assessing this is how to define secondary atrial fibrillation. However, in many studies patients who developed in the setting of acute illness still had a high risk of developing quote unquote clinically significant AF in long-term follow-up. However, this was not necessarily absolute as many patients not necessarily develop AF that could be considered clinically significant. Thus, the clinical question that arises is: how long should we treat a patient with anticoagulation when they have presumed secondary atrial fibrillation. These data seem to suggest that there may be no net overall benefits. In other words, all-comers with secondary atrial fibrillation should not necessarily be forever treated with anti-coagulation. However, this slightly requires clinical trials to evaluate further.                                                 Next we delve into the realm of cardiac mapping and ablation where we view an article by Gaita et al. entitled 'Very long-term outcome following transcatheter ablation of atrial fibrillation. Are results maintained after 10 years of follow-up?', published in Europace last month. While pulmonary vein isolation is a widely accepted approach for treatment of atrial fibrillation, most reported studies review outcomes in terms of freedom of AF over a relatively short time period, generally two to five years. However longer term follow up is inconsistently reported. Gaita et al. sought to review 10 year outcomes amongst 255 patients undergoing ablation in a single center. They noted 52% remainder arrhythmia-free amongst a mixed cohort of both paroxysmal and persistent patients while 10% progressed to permanent atrial fiBrillation. They found that absence of increases in blood pressure, BMI, and fasting glucose was protective against an arrhythmia recurrence.                                                 These findings suggest that in a relatively small cohort of patients limited to a single center that even long-term outcomes after pulmonary vein isolation are generally quite good, exceeding 50%. However, future freedom from atrial fibrillation is heavily tied to control of other risk factors. In other words, if a patient is going to have poor control of diabetes, blood pressure, or gain weight, the benefit of their pulmonary vein isolation over long-term follow-up is likely less. These data thus highlight both the potential long-term benefit of PVI, but also the importance of counseling patients regarding the need for continued management and control of future and existing risk factors.                                                 Staying within the realm of atrial fibrillation we next review an article by Weng et al. entitled 'Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation' published in last month's issue of circulation. The probability of detecting atrial fibrillation in patients based on clinical factors and genetic risk is unknown. Weng et al. sought to clarify whether a combination of clinical and polygenic risk scores could be used to predict risk of developing atrial fibrillation over long-term followup in the Framingham Heart Study. Amongst 4,600 individuals, 580 developed incident atrial fibrillation and had an overall lifetime risk of developing atrial fibrillation of 37%. Those are the lowest risk tertile based on clinical risk factor burden and genetic predisposition had a lifetime risk of 22% versus 48% in the highest. Furthermore, a lower clinical risk factor burden was associated with delayed atrial fibrillation onset. In order to identify patients with atrial fibrillation, before negative sequelae such as stroke occur, patient and physician understanding of risk and monitoring needs is necessary. The fact is that it will be great to identify every single patient who has atrial fibrillation before they have a negative sequela of that atrial fibrillation such as ischemic stroke.                                                 However, performing continuous monitoring of all patients with potential negative sequelae of atrial fibrillation is extraordinarily difficult. The reason is it's excessively costly. We cannot monitor the entire population irrespective of whatever the risk factors are. However, if we're able to identify the highest risk cohorts early on before the atrial fibrillation onsets, this may offer opportunities for use of newer cheaper monitors. The work by Weng et al. suggests one such possible approach combines clinical and polygenic risk scores. Actionability of these data, however, remains to be seen and further validation other cohorts is necessary to clarify generalized ability.                                                 The next article we review is published in last month's issue of the Journal of American College of Cardiology by Lopes at al. entitled 'Digoxin and Mortality in Patients With Atrial Fibrillation. Lopes et al. sought to evaluate the impact of the Digoxin on mortality in patients with atrial fibrillation and the association with the Digoxin serum concentration and heart failure status. They value this association in over 17,000 patients. At baseline 32% were receiving Digoxin. Baseline Digoxin use did not associate with risk of death, but even in these patients a serum concentration of greater than 1.2 nanograms per milliliter was associated with a 56% increase in mortality risk. For each .5 nanogram per milliliter increase in oxygen concentration the hazard ratio increased by 19% for overall mortality. This was irrespective of heart failure status. Furthermore, in patients who are newly started in Digoxin over the follow-up period, the risk and death and sudden death was higher. These data suggests a significant risk associated with Digoxin use for management of atrial fibrillation irrespective of heart failure status. Furthermore, serum valleys above 1.2 require close consideration of dose de-escalation. Whether there is any optimal dose, however, from the study is unclear. These data amongst a host of prior data strongly suggest again strategic use of Digoxin  principally for the management of atrial fibrillation.                                                 Moving on within the realm of atrial fibrillation, we review an article published in last month's issue of Circulation Research by Yan et al. entitled Stress Signaling JNK2 Crosstalk with CaMKII Underlies Enhanced Atrial Arrhythmogenesis. In this more acellular based study the mechanism underlying atrial arrhythmogenesis associated with aging was evaluated. Yan et al. sought to figure out whether the stress response JNK in calcium mediated arrhythmias might contribute to atrial arrhythmogenesis in aged transgenic mouse models. They demonstrated significant increased activity of JNK2 and aging atria, those furthermore associated with rhythmic remodeling. This association was mediated through CaMKII and ryanodine receptor channel function, with activation of the former leading to increased calcium leak mediated by the ladder. This in turn related to increase atrial fibrillation likelihood. Identifying novel targets for atrial fibrillation therapy is critical. Given atrial fibrillation is a complex disease process related to a multitude of risk factors it can be assumed that the contribution of any single factor may be mediated through distinct mechanisms.                                                 Aging in particular as well regarded, but considered to be non-modifiable risk factor for atrial fibrillation. Identifying genes or pathways, the immediate aging associated fibrillation, may take the risk of aging as no longer a non-modifiable thing. The finding of the significance of JNK2 and associate downstream effects with AF risks and aging hearts may hold potential in offering unique therapeutic targets.                                                 Finally, within the realm of atrial fibrillation, we're viewing article by Chen et al. in last month's issue of the Journal of the American Heart Association entitled Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20 Years: The ARIC-NCS Study. Multiple studies have suggested a significant association between atrial fibrillation risk of dementia. However, these studies have limited time follow-up and were often done and predominantly white patients. Thus, the authors sought to use the data from ARIC, the Atherosclerosis Risk in Communities Neurocognitive Study, to assess the risk of cognitive decline associated with atrial fibrillation. Amongst over 12,000 participants, a quarter of whom are black and half of whom are white, they noted 2100 patients developed atrial fibrillation and 1,150 develop dementia over a 20 year follow up period.                                                 There was a significantly greater risk of cognitive decline amongst those who developed atrial fibrillation. In turn incident atrial fibrillation for the follow-up period was associated with a higher risk of dementia even after adjusting for other clinical and cardiovascular risk factors such as incidents that ischemic stroke. These data further strengthened prior evidence of a direct link between atrial fibrillation and risk of cognitive decline and dementia. Understanding this long-term risk raises the need to additionally identify approaches to prevent this occurrence, which in turn is dependent on understanding the underlying mechanisms. The finding that the risk of cognitive decline dementias independent of ischemic stroke events raises concern that either subclinical micro-embolic events or other factors may be playing a role in this risk and in turn raises question as to how best to prevent them. Until better understood, however, the question of whether the association is causal remains to be seen.                                                 Changing gears yet again, we now delve into the realm of ICDs, pacemakers and CRT. Published in last month, issue of Heart Rhythm Tarakji et al. published a paper entitled 'Unrecognized venous injuries after cardiac implantable electronic device transvenous lead extraction.' Overall risk of transvenous lead extraction includes that of potentially fatal venous laceration. The authors sought to evaluate the incidence of venous injury that may be unrecognized based on microscopic study of extracted leads. Amongst 861 leads obtained from 461 patients they noted 80 leads or almost 9%. Amongst 15% of patients showed segments vein on the lead body, most of which were transmural including the tissue layer. However, in terms of clinical significance, only 1% had need for emergent surgical intervention for clinically significant venous laceration. Risk factors for having the entire vein on the lead included age of lead, ICD leads, and the use of the laser sheath.                                                 These findings suggest that there may be a high incidence of subclinical venous injury after lead extraction though rarely resulting clinically apparent sequelae. As would be expected, venous injury, including transmural removal of portions of the vein traversed by the lead, was more common amongst older leads, which generally more often require laser sheets and ICD leads. The question is however, whether this carries any direct clinical implications. One they may be considered is the potential additive risk of an advancing new lead through the same venous channel, particularly in the setting of potential transmural venous injury that already exists.                                                 Next in last month's issue of Heart Rhythm we review an article by Sharma at al. entitled 'Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac resynchronization therapy: A multicenter experience.' The use of resynchronization therapy for treatment of patients with heart failure and wide QRS has been shown to offer morbidity and mortality benefits. However, many patients maybe non-responders, and recent studies on His bundle pacing of suggested potential clinical benefits. His bundle pacing essentially only requires one pacing catheter attached within the region of the His bundle Sharma et al. sought to evaluate the safety and success rates of His bundle pacing for patients who have either failed standard resynchronization therapy or in whom most tried as a primary intervention. They noted His bundle pacing was successful in 90% of patients with reasonable myocardial and His bundle capture thresholds. Patients in both groups exhibits significant narrowing of QRS morphology and improvement in left ventricular ejection fraction from a mean of 30 to 43%. However, a total of seven patients had lead related complications.                                                 These database on a retrospective analysis of two types of patients, those failing standard biventricular therapy, and those on whom his bundle pacing was attempted as a primary modality suggest overall safety and efficacy in a handful of experienced centers. The promise of His bundle pacing is that a may allow for more effective resynchronization than standard approaches. The high rate of success suggests that His bundle pacing maybe both safe and reasonable to pursue. However randomized trials across more centers are needed to fully prove its benefit, particularly as a primary modality of treatments.                                                 Next we review ICDs and chronic kidney disease. In last month's issue of JAMA cardiology by Bansal at al. entitled 'Long-term Outcomes Associated With Implantable Cardioverter Defibrillator in Adults With Chronic Kidney Disease.' While the benefit of ICDs in patients with low EF is widely recognized, modifying factors that may increase risk of death are not as well defined. These include things like advanced age and chronic kidney disease. Bansal et al. sought to evaluate long-term outcomes and ICD therapy in patients with chronic kidney disease. In retrospective study of almost 5,900 ambulatory patients amongst whom 1550 had an ICD, they found no difference in all cause mortality. However, ICD placement was associated with an increased risk of subsequent hospitalization due to heart failure or any cause hospitalization.                                                 In light of recent studies such as DANISH the robust sense of ICD benefit is being questioned. One of the thoughts for the absence of similar benefit to prior studies lies in the improving care of ambulatory heart failure patients. In patients with chronic kidney disease several questions rises to the risk with ICD, including infectious risk in dialysis patients and the concomitant mortality risk with renal dysfunction. The author suggested in retrospective study, no incremental benefit of ICDs in patients with chronic kidney disease and perhaps some element of added risk is related to hospitalization. However, this study has several limitations. It is retrospective and many patients received ICDs may have been perceived to be sicker in some way. Thus care must be taken in interpretation, but consideration of randomized studies to adjudicate benefit are likely necessary.                                                 Finally, within the realm of devices, we reviewed an article by Tayal et al. entitled "Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS Complexes.' publishing the Journal of American College of Cardiology last month. Several parameters have been stressed to identify benefit of resynchronization therapy in patients with wide QRS include cross correlation analysis with tissue doppler imaging. However, many patients may have evidence in mechanical dyssynchrony even in the absence of an apparent wide QRS thus Tayal et al. sought to evaluate the benefit of resynchronization therapy amongst 807 patients with heart failure and a narrow QRS mean criteria in a randomized study. Of the 807 46% had delayed mechanical activation. Those without delay mechanical activation had underwent we standardization therapy and were associated with worse overall outcomes likely due to new delayed mechanical activation potentially related to CRT pacing. These data support the absence of a role for resynchronization therapy in patients with a narrow QRS. This is expected as resynchronization therapy likely offers the most benefit in patients with mechanical dyssynchrony that results from electrical dyssynchrony.                                                 Since by its very nature resynchronization therapy relies on non physiologic cardiac pacing thus compared to normal cardiac activation the nature of resynchronization pacing is desynchronization. These data support the absence of a role for resynchronization therapy in patients with heart failure and narrow QRS complexes.                                                 Moving on to cellular electrophysiology we review an article by Kozasa et al. published in last month's issue of Journal of Physiology entitled 'HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node.' Heart rate is controlled by an interplay between sympathetic and parasympathetic components. In turn HCN4 abnormalities have been implicated in congenital sick sinus syndrome. The authors sought to clarify the contribution of HCN4 to sinus node autonomic regulation. They created a novel gain-of-function mouse where the HCN4 activity could be modulating from zero to three times normal. They then evaluated ambulatory heart-rate variability and responsive heart rate to vagus nerve stimulation. They found HCN4 over-expression did not increase heart rate, but attenuated heart-rate variability. It also attenuated bradycardic response to vagus nerve stimulation. Knockdown of HCN4 in turn lead to sinus arrhythmia and enhanced parasympathetic response. These data suggest HCN4 attenuates sinus node response to vagal stimuli thus stabilizing spontaneous firing of the node. The clinical application of this remain to be seen but are maybe important in that they highlight a mechanism for a heretofore poorly understood mechanism for how exactly HCN4 abnormalities may lead to sick sinus syndrome.                                                 Within the realm of ventricular arrhythmias we highlighted a number of articles published this past month. The first article we review was published in last month's issue of JACC clinical electrophysiology, entitled characterization of the electrode atomic substrate and cardiac sarcoidosis: correlation with imaging findings of scarring inflammation published by [inaudible 00:41:40] et al. In patients with cardiac sarcoidosis one of the questions is how to define the electronic atomic substrate, particularly before we entered the electrophysiology laboratory. Both active inflammation and replacement fibrosis maybe be seen in patients. The authors evaluated in 42 patients with cardiac sarcoidosis, the association between an abnormal electrograms and cardiac imaging findings including PET and Computed Tomography, as well as Cardiac MRI. They noted that amongst these 40 patients, a total of 21,000 electrograms were obtained, and a total of 19% of these were classified as abnormal. Most of the abnormalities occurred in the basal paravalvular segments and intraventricular septum. They further noted that many of these abnormalities in terms of electrograms were located outside the low voltage areas, particularly as it relates to fractionation. In about 90% of patients they notice late gadolinium enhancements and they noted abnormal FDG uptakes suggesting active inflammation in about 48%.                                                 However, it should be noted that only 29 of the 42 patients underwent cardiac imaging. Segments with abnormal electrograms tended to have more late gadolinium enhancement evidence scar transmurality, and also they noted that the association of abnormal PET scan did not necessarily occur with abnormal electrograms. Thus, they concluded that in patients with cardiac sarcoidosis and ventricular tachycardia pre-procedural imaging with cardiac MRI could be useful in detecting electroanatomic map abnormalities that may in turn be potential targets for substrate ablation. However, they were more likely associated with more scar transmurality and lower degrees of inflammation on PET scanning. These data are important in that they highlight potential non-invasive means by which to understand where substrate might occur in patients with the cardiac sarcoidosis. It is well recognized that cardiac sarcoidosis is associated with increased risk of ventricular arrhythmias. These risks have increased ventricular arrhythmias, might be targetable with ablation. Newer therapies might even offer non invasive means by which to perform ablation in patients best. Thus if we could identify non based on mechanisms of identifying the substrate, this will be even more critical.                                                 The critical findings of this particular paper lie in noting that most of the abnormalities still is in intra ventricular sePtum in basal segments, and also that it is MRI in late gadolinium enhancement and associates more with the abnormal electrograms. Interestingly, the absence of inflammation correlating with the presence of more abnormal electrograms suggests that it is not so much the act of inflammation as being reflected in the endocardial map, but the existence of scar.                                                 Next, again within JACC clinical electrophysiology we review an article by Porta-Sánchez et al. entitled 'Multicenter Study of Ischemic Ventricular Tachycardia Ablation With Decrement Evoked Potential Mapping With Extra Stimulus.' The authors sought to conduct a multicenter study of decrement evoked potential base functional tech ventricular tachycardia substrate modification to see if such mechanistic and physiologic strategies could result in reduction in VT burden. It is noted that really only a fraction of the myocardium in what we presume to be substrate based on the presence of low voltage areas are actually involved in the initiation and perpetuation of VT. Thus if we can identify the critical areas within the presumed substrate for ablation, this would be even a better way of potentially honing in on our targets. They included 20 consecutive patients with ischemic cardiomyopathy. During substrate mapping fractionated late potentials were targeted and an extra stimulus was provided to determine which display decrements. All patients underwent DEEP focus ablation with elimination being correlated with VT non-inducibility after radio-frequency ablation. Patients were predominantly male, and they noted that the specificity of these decrement evoked potentials to detect the cardiac isthmus for VT was better than that of using late potentials alone. They noted 15 of 20 patients were free of any VT after ablation of these targets over six months of follow-up, and there was a strong reduction in VT burden compared to six months pre ablation.                                                 They concluded that detriment evoked potential based strategies towards ablation for ventricular tachycardia might identify the functional substrate and those areas most critical to ablation. They in turn regarded that by its physiologic nature it offers greater access to folks to ablation therapies.                                                 This publication is important in that it highlights another means by which we can better hone in on the most critical regions for substrate evaluation in patients with ventricular tachycardia. The fact is more extensive ablation is not necessarily better and might result in increased risk of harm if we think about the potential effects of longer ablations or more ablation lesions. Thus if we could identify ways of only targeting those areas that are most critical to the VT circuits, we could perhaps short and ablation procedural time, allow for novel ways of approaching targeted ablation with limited amounts of ablation performed, or perhaps even improve overall VT outcomes by knowing the areas that are most critical to ensure adequate ablation therapy provided. However, we need to understand that this is still a limited number of patients evaluated in a non randomized manner. Thus whether or not more extensive ablation performed might have been better is as of yet unclear                                                 Staying within the realm of ventricular tachycardia we review an article published in last month's issue of Heart Rhythm by Winterfield et al. entitled the 'Impact of ventricular tachycardia ablation on healthcare utilization.' Catheter ablation of atrial tachycardia has been well accepted to reduce recurrent shocks in patients with ICDs. However, this is a potentially costly procedure, and thus effect on overall long-term health care utilization remains to be seen. The authors sought to evaluate in a large scale real world retrospective study the effect of VT ablation on overall medical expenditures in healthcare utilization. A total 523 patients met study inclusion criteria from the market scan database. After VT ablation median annual cardiac rhythm related medical expenditures actually decreased by over $5,000. Moreover the percentage of patients with at least one cardiac rhythm related hospitalization an ER visit decreased from 53 and 41% before ablation respectively, to 28 and 26% after ablation. Similar changes we're seeing in number of all cause hospitalizations and ER visits. During the year before VT ablation interestingly there was an increasing rate of healthcare resource utilization, but a drastic slowing after ablation.                                                 These data suggests that catheter ablation may lead to reduced hospitalization in overall healthcare utilization. The importance of these findings lies in understanding why we do the things we do. We can provide a number of therapies to patients, but we seek two different effects. One is the individual effect of improving their particular health. The second thing is trying to avoid increasing healthcare expenditures on a population level and making sure resources are utilized. If we can reduce recurrent hospitalizations and overall healthcare expenditure in patients by providing a therapy in addition to provide individual benefit, this is the optimal situation. These data suggests that VT ablation might provide such a benefits, that in fact it reduces overall healthcare utilization while improving overall outcomes.                                                 Next and finally within the realm of ventricular arrhythmias, we review more on the basic side the role of Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias, published by Verdonschot et al. in last month's issue of European Heart Journal. It is known now that truncating Titin variants might be the most prevalent genetic cause of dilated cardiomyopathy. Thus, the authors sought to study clinical parameters and long term outcomes related to Titin abnormalities in dilated cardiomyopathy. They reviewed 303 consecutive and extensively phenotype dilated cardiomyopathy patients who underwent cardiac imaging, Holter monitoring, and endomyocardial biopsy and in turn also underwent DNA sequencing of 47 cardiomyopathy associated genes. 13% of these patients had Titin abnormalities. Over long-term followup they noted that these patients had increased ventricular arrhythmias compared to other types of dilated cardiomyopathy, but interestingly, they had similar survival rates. Arrhythmias in those Titin abnormal patients were most prominent in those who were subjected to an additional environmental trigger, including viral infection, cardiac inflammation, other systemic disease or toxic exposure. They also noted the cardiac mass was relatively reduced in titan admirable patients.                                                 They felt that all components of the mitochondrial electron transport chain we're simply up-regulated in Titin abnormal patients during RNA sequencing and interstitial fibrosis was also augmented. As a result, they concluded that Titin variant associated dilated cardiomyopathy was associated with an increased risk of ventricular arrhythmias, and also with more interstitial fibrosis. For a long time we have reviewed all non ischemic cardiomyopathy as essentially equal. However, more recent data has suggested that we can actually hone in on the cause. In turn, if we hone in on the cause, we might be able to understand the effects of specific therapies for ventricular arrhythmias based on that underlying cause. Patchy fibrosis might not be as amenable, for example, to ablation as discreet substrate that we might see in infarct related VT. Understanding the relative benefit in very specific types of myopathies might hold benefit in understanding how to, one, risk stratify these patients, and two, understand what type of therapy, whether pharmacologic or ablative, might result in greatest benefit to the patients.                                                 Changing gears entirely now to the role of genetics, we review multiple articles in various genetic syndromes published this past month. First, we reviewed an article by Providência et al. published in the last month's issue of heart entitled 'Impact of QTc formulae in the prevalence of short corrected QT interval and impact on probability and diagnosis of short QT syndrome.' The authors sought to assess the overall prevalence of short corrected QT intervals and the impact on diagnosis of short QT syndrome using different methods for correcting the QT interval. In this observational study they reviewed the sudden cardiac death screening of risk factors cohorts. They then applied multiple different correction formulae to the ECGs. They noted that the prevalence of individuals with the QTc less than 330 and 320 was extremely low, namely less than .07 and .02% respectively. They were also more frequently identified using the Framingham correction. The different QTc correction formulae could lead to a shift of anywhere from 5 to 10% of individuals in the cohort overall.                                                 They further noted, that based on consensus criteria, instead of 12 individuals diagnosed with short gut syndrome using the Bazett equation, a different number of individuals would have met diagnostic criteria with other formulae, 11 using Fridericia, 9 with Hodges, and 16 using the Framingham equation. Thus, they noted that overall the prevalence of short QT syndrome exceedingly low and an apparently healthy adult population. However, reclassification as meeting criteria might be heavily dependent on which QT correction formula is used. The importance of these findings is that not all QTs are created equal.                                                 Depending on how you compute the QT interval in which formula to use may affect how you actually risk characterize a patient. Unfortunately, these data do not necessarily tell us which is the right formula, but this highlights that it might be relevant to in the future evaluate the role of different formulae and identifying which is the most necessary to classify a patient.                                                 Moving on to an article published in last month's issue of the journal of clinical investigation by Chai et al. we review an article entitled 'Physiological genomics identifies genetic modifiers of Long QT Syndrome type 2 severity.' Congenital Long QT Syndrome is a very well recognized, inherited channelopathy associated life-threatening arrhythmias. LQTS type 2 is specifically caused by mutations in casein to encoding the potassium channel hERG. However, even with the mutation not all patients exhibit the same phenotype. Namely some patients are more at risk of life threatening arrhythmias in spite of having the same mutation as others who do not exhibit the same severity phenotype. The authors sought to evaluate whether specific modifiable factors within the remaining genetic code might be modifying the existing mutation. Thus, they sought to identify contributors to variable expressivity in an LQT 2 family by using induced pluripotent stem cell derived cardiomyocytes and whole exome sequencing in a synergistic manner.                                                 They found that patients with severely effected LQT 2 displayed prolonged action potentials compare to sales from mildly effected first-degree relatives. Furthermore, stem cells derived from patients were different in terms of how much L-type calcium current they exhibited. They noted that whole exome sequencing identified variants of KCNK17 and the GTP-binding protein REM2 in those patients with more severe phenotypes in whom greater L-type calcium current was seen. This suggests that abnormalities or even polymorphisms in other genes might be modifying the risk attributed to by mutations in the primary gene. This showcases the power of combining complimentary physiological and genomic analysis to identify genetic modifiers and potential therapeutic targets of a monogenic disorder. This is extraordinarily critical as we understand on one level that when we sequence a monogenic disorder that there might exist variants of uncertain significance, namely they have not been classified as disease causing, but could be. In turn, we also recognize that mutations in a family might effect different relatives differently. However, why this is has been relatively unclear.                                                 If we can understand and identify those patients who are most at risk of dangerous abnormal rhythms, this will be useful in how much to follow them, and what type of therapy to use in them. The fact that other genes might modify the risk even in the absence of specific mutations, suggests that novel approaches to characterizing the risk might help for the risk modified patients classification in general. Clinical use, however, remains to be seen.                                                 Moving on from long QT, we evaluate 'The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy' noted in last month's issue of the Journal of American College of Cardiology and published by Papadakis et al. It is well known, the negative autopsies are not uncommon in patients, however, families might be wondering how at risk they are. Thus, the authors sought to assess the impact of systematic ajmaline provocation testing using high right precordial leads on the diagnostic yield Brugada syndrome in a large cohort of Sudden Arrhythmic Death syndrome families. Amongst 303 families affected by Sudden Arrhythmic Death Syndrome evaluation was done to determine whether or not there was a genetic inherited channelopathy cause. An inherited cardiac disease was diagnosed in 42% of the families and 22% of relatives Brugada syndrome was the most prevalent diagnosis overall amongst 28% of families. Ajmaline testing was required, however, to unmask the Brugada Syndrome in 97% of diagnosed individuals. Furthermore, they use of high right precordial leads showed a 16% incremental diagnostic yield of ajmaline testing for diagnosing Brugada syndrome.                                                 They further noted that a spontaneous type 1 regard or pattern or a clinically significant rhythmic event developed in 17% of these concealed regardless syndrome patients. The authors concluded the systematic use of ajmaline testing with high right precordial leads increases the yield of Brugada Syndrome testing in Sudden Arrhythmic Death Syndrome families. Furthermore, they noted that assessments should be performed in expert centers or patients could also be counseled appropriately. These findings are important and one of the big questions always becomes how aggressively to test family members of patients or of deceased individuals who experienced sudden arrhythmic death. Many of these patients have negative autopsies, and genetic autopsy might not be possible due to lack of tissue or blood products that can be adequately tested.                                                 The data here suggest that amongst a group of 303 sudden arrhythmic death, families that Brugada Syndrome is by far the most frequent diagnosis. If an inherited cardiac disease was identified. In turn, it is not ECG alone or echo alone that helps identify them, but requires drug provocation testing in addition to different electrode placements. Whether or not this will consistently offer benefit in patients in general or my result in overcalling remains to be seen next within the realm of genetic predisposition.                                                 We view an area where we don't know if there's a genetic predisposition in article published by Tester et al. entitled Cardiac Genetic Predisposition in Sudden Infant Death Syndrome in last month's issue of the journal of american college of cardiology. Sudden Infant Death Syndrome is the leading cause of post-neonatal mortality and genetic heart diseases might underlie some cases of SIDS. Thus the authors sought to determine the spectrum and prevalence of genetic heart disease associated mutations as a potential monogenic basis for Sudden Infant Death Syndrome. They study the largest cohort to date of unrelated SIDS cases, including a total of 419 individuals who underwent whole exome sequencing and targeted analysis for 90 genetic heart disease susceptibility genes. Overall, 12.6% of these cases had at least one potentially informative genetic heart disease associated variants. The yield was higher in those mixed European ancestry than those of European ancestry.                                                 Infants older than four months were more likely to host a potentially informative gene. Furthermore, they noted that only 18 of the 419 SIDS cases hold a [inaudible 01:01:26] or likely pathogenic variant. So in other words, only 4% of cases really had a variant that they could say was distinctly pathogenic or likely pathogenic. Thus, overall, the minority of SIDS cases have potentially informative variant in genetic heart disease susceptibility gene, and these individuals were mostly in the 4 to 12 month age group. Also, only 4% of cases had immediately clinically actionable variance, namely a variant, which is well recognized as pathogenic and where we could actually say that a specific therapy might have had some effect. These findings can have major implications for how best to investigate SIDS cases in families. It might suggest that SIDS cases where the individual was older, nearly 4 to 12 months of age might have a greater yield in terms of identifying variance.                                                 While this might not affect the deceased in fit, it might affect, families are planning on having another child in whom a variant can be identified.                                                 Finally, within the realm of genetics, we review an article published in last month's issue of Science Advances by Huang. et al. entitled 'Mechanisms of KCNQ1 Channel Dysfunction in Long QT Syndrome Involving Voltage Sensor Domain Mutations'. Mutations that induce loss of function of human KCNQ1 underlie the Long QT Syndrome type 1. While hundreds of mutations have been identified the molecular mechanism by which they result in impaired function are not as well understood. The authors sought to investigate impact of 51 specific variants located within the voltage sensor domain and emphasized effect on cell surface expression, protein folding, and structure. For each variant efficiency of trafficking of the plasma membrane, impact of proteasome inhibition, and protein stability were evaluated. They noted that more than half of the loss of function mutations were seen to destabilized structure of the voltage sensor domain, generally accompanied by mistrafficking and degradation by the proteasome.                                                 They also noted that five of the folding defective Long QT Syndrome mutant sites were located in the S0 helix, where they tend to interact with a number of other loss of function mutation sites in other segments of the voltage sensor domain. They suggested these observations reveal a critical role for the S0 helix as a central scaffold to help organize and stabilized KCNQ1 overall. They also note the importance of these findings is that mutation-induced destabilization of membrane proteins may be a more common cause of disease functioning in humans. The importance of these findings lies in better understanding why specific mutations lead to appa

This episode, Wade Pitts interviews Sifu Paul Wang — a practitioner of WingChun. Paul has a bit of a “traditional, non-traditional” background in the martial arts. Originally born in Taiwan, his family immigrated to the United States, moving to Utah, then to Chicago. He got his first exposure to the martial arts from Judo, then later moved back to Taiwan where he became more immersed in the martial arts. Moving once more, back to the U.S., he began learning integrative biology with an emphasis on human locomotion, biomechanics, and biodynamics.   While studying to become a doctor, he had taken a class in WingChun and discovered that the style was one of the most efficient translations of body mechanics and results. His interest began to shift to Chinese and integrative medicine which better complimented his interests in martial arts, as they shared many of the same philosophies. He went on to earn his Master's and Doctorate in Acupuncture and Chinese Medicine, and is now the National Instructor at the International Academy of WingChun, in Berkeley, California.   Wade and Paul talk about Paul's diverse background in medicine, how his interest in biomechanics blends perfectly with WingChun, how martial arts has helped him explore his spiritual and extroverted side, what the move from academic to instructor of a martial arts was like, his daily practices, and his advice on pursuing martial arts and setting goals for yourself.   Key Takeaways: [1:25] Paul Wang's introduction to the martial arts. [3:33] Paul's process coming back to the States and transitioning from his original path of western medicine to eastern medicine. [7:20] How Paul's interest in biomechanics blends perfectly with the main style that he practices, WingChun. [10:11] How martial arts helped bring Paul come out of his introversion and help him navigate his spirituality. [12:01] How Paul got started teaching martial arts. [14:16] How that transitioned to Paul becoming an instructor at a martial arts school. [15:58] What the first couple of years were like at the martial arts school. [21:18] How Paul has seen WingChun developing and where he sees the style heading. [30:13] Paul's daily practices. [39:23] More about Paul's school and where to learn more. [41:00] Additional advice from Paul: Where to gather inspiration, how to persevere, and why you should set goals.   Mentioned in this Episode: WingChunUS.com SifuPaulWang.com  

Paul Wang:         Welcome to the monthly podcast “On The Beat”, for Circulation: Arrhythmia and Electrophysiology. I am Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field.                                 In our first article, Adetola Ladejobi and associates studied 1,433 patients, between 2000 and 2012, who were discharged alive after sudden cardiac arrest. A reversible and correctable cause was identified in 792 patients, or 55%. A reversible cause for sudden cardiac arrest was defined as significant electrolyte or metabolic abnormality, evidence of acute myocardial infarction or ischemia, recent initiation of antiarrhythmic drug, or illicit drug use, or other reversible circumstances.                                 Of the 792 sudden cardiac arrest survivors, due to reversible or correctable cause, 207 or 26% of the patients received an ICD after their indexed sudden cardiac arrest. During a mean follow-up of 3.8 years, 319 or 40% of patients died. ICD implantation was highly associated with a lower all-cause mortality, p < 0.001, even after correcting for unbalanced baseline characteristics.                                 In subgroup analyses, only patients with sudden cardiac arrest, were not associated with myocardial infarction, extracted benefit from the ICD, p < 0.001.                                 The authors concluded that in survivors of sudden cardiac arrest, due to a reversible and correctable cause, ICD therapies associated with lower all-cause mortality, except if the sudden cardiac arrest was due to myocardial infarction.                                 Further prospect of multi-center randomized control trials will be needed to confirm this observation.                                 In our next study, Carlo Pappone and associates, studied 81 patients with persistent atrial fibrillation, randomized to undergo high density electrophysiological mapping, to identify repetitive regular activities, before modified circumferential pulmonary vein ablation, or modified circumferential pulmonary vein ablation alone. The primary endpoint was freedom from arrhythmia recurrence at one year.                                 In the 81 patients with persistent atrial fibrillation, there were 479 regions exhibiting repetitive regular activities in these patients, or 5.9 repetitive regular activities per patient. There were 232 regions in the mapping group, which consisted of 41 patients, and 247 regions in the control group, consisting of 40 patients. Overall, 39% of the repetitive regular activities were identified within pulmonary veins, whereas 61% were identified in non-pulmonary vein regions.                                 Mapping-guided ablation resulted in higher arrhythmia termination rate, as compared to conventional strategy, 61% vs. 30%, p < 0.007. Total RF duration, mapping, and fluoroscopy times were not significantly different between the groups. No major procedure related adverse events occurred.                                 After one year, 73% of the mapping group of patients were free of recurrences, compared to 50% of the control group, p = 0.03.                                 The authors concluded that targeted ablation of regions showing repetitive regular activities provided adjunctive benefit in terms of arrhythmia freedom at one year in treatment of patients with persistent atrial fibrillation. These findings should be confirmed by additional larger randomized multi-centered studies.                                 In the next article, Maciej Kubala and associates examine repolarization abnormalities in 40 patients with arrhythmogenic right ventricular cardiomyopathy, comparing extent and location of abnormal T-waves of one millimeter or greater in depth, downsloping elevated ST segment in two or more adjacent leads to the area and location of endocardial bipolar and unipolar, and epicardial bipolar voltage abnormalities. They found an abnormal unipolar right ventricular endocardial area of 33.4% with presence in eight patients without negative T-waves. Patients with negative T-waves extending beyond V3, seen in 20 patients, had larger low bipolar and unipolar endocardial areas, and larger epicardial low bipolar areas, compared to those with negative T-waves limited to leads V1 to V3.                                 ECG localization of negative T-waves regionalized to the location of substrate. Patients with downsloping elevated ST segment, all localized to leads V1, V2 had more unipolar endocardial abnormalities involving outflow in mid-right ventricle, compared to patients without downsloping elevated ST segment.                                 The authors concluded that in arrhythmogenic right ventricular cardiomyopathy, abnormal electric current areas were proportional to the extent of T-wave inversion on the 12 lead electrocardiogram. Marked voltage abnormalities can exist without repolarization changes. Downsloping elevated ST segment patterns in V1 and V2 occurs with more unipolar endocardial voltage abnormalities, consistent with more advanced trans neural disease.                                 In the next manuscript, Teresa Oloriz and associates examine the timing and value of program stimulation after catheter ablation for ventricular tachycardia. They performed 218 program ventricular stimulations six days after ablation in 210 consecutive patients, 48% with ischemic cardiomyopathy in the median left ventricular ejection fraction of 37%. After ablation, ICDs were programmed according to NIPS results. Class A were noninducible, Class B non documented inducible VT, and Class C documented inducible VT. Concordance between the programmed ventricular stimulation at the end of the procedure and at six days was 67%. The positive predictive value and negative predictive value were higher for the programmed ventricular stimulation at day six. Ischemic patients and those with preserved ejection fraction showed the highest negative predictive value.                                 Among noninducible patients at the end of the procedure, but inducible at day six, 59 patients had VT recurrence at one year follow-up. Recurrences were 9% when both studies were noninducible. There were no inappropriate shocks, incidents of syncope with 3%, none harmful. The rate of appropriate shocks per patient per month according to NIPS was significantly reduced, comparing the month before and after the ablation.                                 The authors concluded that programmed ventricular stimulation at day six predicts VT recurrence.                                 In the next study, Tor Biering-Sørensen and associates examined ECG global electrical heterogeneity, GEH, in its longitudinal changes, are associated with cardiac structure and function, in their Atherosclerosis Risk and Community study, ARIC, consisting of 5,114 patients, 58% which were female and 22% African Americans. Using the resting 12-lead ECGs, and echocardiographic assessments of left ventricular ejection fraction, global strain, left ventricular mass index, end diastolic volume index, end systolic volume index at visit five.                                 Longitudinal analysis included ARIC participants with measured GEH at visits one to four. GEH was quantified by spatial ventricular gradient, the QRST angle, and the sum of the absolute QRST integral. Cross sectional and longitudinal regressions were adjusted for manifest subclinical cardiovascular disease.                                 Having four abnormal GEH parameters was associated with a 6.4% left ventricular ejection fraction decline, a 24.2 gram/meter square increase in left ventricular mass index, a 10.3 milliliter/meter square increase in left ventricular end diastolic volume index, and a 7.8 milliliter/meter square increase in left ventricular end systolic index. All together, clinical and ECG parameters accounted for approximately one third of the left ventricular volume in 20% of the systolic function variability.                                 The associates were significantly stronger in patients with subclinical cardiovascular disease. The QRST integral increased by 20 millivolts/meter second for each three year period participants who demonstrated left ventricular dilatation at visit five. Sudden cardiac death victims demonstrated rapid GEH worsening, while those with left ventricular dysfunction demonstrated slow GEH worsening.                                 The authors concluded that GEH is a marker of subclinical abnormalities in cardiac structure and function.                                 In the next manuscript, Takumi Yamada and associates studied 19 patients with idiopathic ventricular arrhythmias, originating in the parietal band in 14 patients, in the septal band in 5 patients. Among 294 consecutive patients with right ventricular arrhythmia origins, parietal band and septal band ventricular arrhythmias exhibited a left bundle branch block, with left inferior in 12 patients', superior in 2 patients' axes, in left or right inferior axis pattern in four and one patients respectively.                                 In Lead 1, all parietal band ventricular arrhythmias exhibited R-waves, while septal band ventricular arrhythmias often exhibited S-waves. A QS pattern in lead AVR, in the presence of a knock in the mid QRS were common in all infundibular muscle ventricular arrhythmias. During infundibular muscle ventricular arrhythmias, a far-field ventricular electrogram, with an early activation, was always recorded in the His bundle region, regardless of the location of ventricular arrhythmia regions. With 9.2 radiofrequency applications in a duration of 972 seconds, catheter ablation was successful in 15 of the 19 patients. Ventricular arrhythmias recurred in four patients during a fallout period of 43 months.                                 In the next paper, Uma Mahesh Avula and associates examine the mechanisms underlying spontaneous atrial fibrillation, in an Ovine model of left atrial myocardial infarction. The left atrial myocardial infarction was created by ligating the atrial branch of the left anterior descending artery. ECG loop recorders were implanted to monitor atrial fibrillation episodes.                                 In seven sheep, Dantrolene, a Ryanodine receptor blocker, was administered in vivo, during the observation period. The left atrial myocardial infarction animals experienced numerous episodes of atrial fibrillation during the eight day monitoring period, that were suppressed by Dantrolene. Optical mapping showed spontaneous focal discharges originating through the ischemic/normal-zone border. These spontaneous focal discharges were calcium driven, rate dependent, and enhanced by isoproterenol, but suppressed by Dantrolene.                                 In addition, these spontaneous focal discharges initiated atrial fibrillation-maintaining reentrant rotors anchored by marked conduction delays at the ischemic/normal-zone border. Nitric oxide synthase one protein expression decreased in ischemic zone myocytes, or NADPA oxidase in xanthine oxidase enzyme activities in reactive oxygen species increased. Calmodulin aberrantly increased, Ryanodine binding to cardiac Ryanodine receptors in the ischemic zone. Dantrolene restored the physiologically binding of Calmodulin to the cardiac Ryanodine receptors.                                 The authors concluded that atrial ischemia causes spontaneous atrial fibrillation episodes in sheep, caused by spontaneous focal discharges that initiate re-entry. Nitroso redox imbalance in the ischemic zone is associated with intensive reactive oxygen species production, and altered the Ryanodine receptor responses to Calmodulin. Dantrolene administered normalize the Calmodulin response and prevents left atrial myocardial infarction, spontaneous focal discharges in atrial fibrillation initiation.                                 In the next study, Wouter van Everdingen and associates examine the use of QLV for achieving optimal acute hemodynamic response to CRT with a quadripolar left ventricular lead. 48 heart failure patients with left bundle branch block were studied. Mean ejection fraction 28%, mean QRS duration 176 milliseconds. Immediately after CRT implantation, invasive left ventricular pressure volume loops were recorded during biventricular pacing, with each separate electrode at four atrial ventricular delays.                                 Acute CRT response, measured as a change in stroke work compared to intrinsic conduction, was related to the intrinsic interval between the Q on the electrocardiogram and the left ventricular sensing delay, that is the QLV, normalized for the QRS duration, resulting in QLV over QRS duration in the electrode position.                                 QLV over QRS duration was 84% and variation between the four electrodes was 9%. The change in stroke work was 89% and varied by 39% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position in a high QLV to QRS duration ratio had a significant association with a large change in stroke work, all P less than 0.01.                                 In a combined model, only QLV over QRS duration remained significantly associated with a change in stroke work, P less than 0.5. However, a direct relationship between QLV over QRS duration in stroke work was only seen in 24 patients, while 24 other patients had an inverse relation.                                 The authors concluded that a large variation in acute hemodynamic response indicates that the choice of stimulated electrode on the quadripolar electrode is important. Although QLV to QRS duration ratio was associated with acute hemodynamic response at a group level, it cannot be used to select the optimal electrode in the individual patient.                                 In the next study, Antonio Pani and associates conducted a multi-centered prospective study evaluating the determinance of zero-fluoroscopy ablation of supraventricular arrhythmias. They studied 430 patients with an indication for EP study and/or ablation of SVT. A procedure was defined as zero-fluoroscopy when no fluoroscopy was used. The total fluoroscopy time inversely was related to number of procedures previously performed by each operator since the study start. 289 procedures, or 67%, were zero-fluoro. Multi-variable analyses identified as predictors of zero-fluoro was the 30th procedure for each operator, as compared to procedures up to the ninth procedure, the type of arrhythmia, AVNRT having the highest probability of zero-fluoro, the operator, and the patient's age. Among operators, achievement of zero-fluoro varied from 0% to 100%, with 8 operators, or 23%, achieving zero-fluoro in 75% of their procedures. The probability of zero-fluoro increased by 2.8% as the patient's age decreased by one year. Acute procedural success was obtained in all cases.                                 The authors concluded that the use of 3D mapping completely avoided the use of fluoroscopy in most cases, with very low fluoro time in the remaining, and high safety and effectiveness profiles.                                 In the next paper, Demosthenes Katritsis and associates examine the role of slow pathway ablation from the septum as an alternative to right-sided ablation. Retrospectively, 1,342 undergoing right septal slow pathway ablation for AV nodal reentry were studied. Of these, 15 patients, 11 with typical and 4 with atypical AVNRT, had a left septal approach following unsuccessful right sided ablation, that is, the righted left group. In addition, 11 patients were subjected prospectively to a left septal only approach for slow pathway ablation, without previous right septal ablation, that is, left group. Fluoroscopy times in the right and left group, and the left groups were 30.5 minutes and 20 minutes respectively, P equals 0.6. The rate of [inaudible 00:18:24] current delivery time for comparable, 11.3 minutes and 10.0 minutes respectively.                                 There are no additional ablation lesions at other anatomical sites in either group, and no cases of AV block were encountered. Recurrence rate for arrhythmias in the right and left group was 6.7% and 0% in the left group, in the three months following ablation.                                 The authors concluded that the left septal anatomical ablation of the left inferior nodal extension is an alternative to ablation of both typical and atypical AV nodal reentry when ablation at the right posterior septum is ineffective.                                 In our next study, Mark Belkin and associates reported prior reports of new-onset device-detected atrial tachyarrhythmias. Despite the clear association between atrial fibrillation and the risk of thromboembolism, the clinical significance of new-onset device-detected atrial tachyarrhythmias and thromboembolism remains disputed.                                 The authors aim to determine the risk of thromboembolic events in these patients. Using the Ovid Medline, Cochrane, SCOPUS databases to identify 4,893 reports of randomized control trials, perspective or retrospective studies of pacemaker and defibrillator patients reporting the incidence of device detected atrial tachyarrhythmias.                                 The authors examine 28 studies, following a total of 24,984 patients. They had an average age of 69.9 years and a mean study duration of 21.8 months. New-onset device-detected atrial tachyarrhythmias was observed in 23% of patients. Among nine studies, consisting of 8,181 patients, reporting thromboembolism, the absolute incidence was 2.1%. Thromboembolic events were significantly greater among patients with new-onset device-detected arrhythmias, with a relative risk of 2.88, compared to those who had less than one minute of tachyarrhythmias, 1.77 risk ratio.                                 The authors concluded that new-onset device-detected atrial tachyarrhythmias is common, affecting close to one quarter of all patients with implanted pacemakers and defibrillators.                                 In our last paper, Sanghamitra Mohanty and associates performed a meta-analysis systematically evaluating the outcome of pulmonary vein isolation with and without thermoablation in patients with atrial fibrillation. For pulmonary vein ablation alone, only randomized trials conducted in the last three years reporting single procedure success rates, off antiarrhythmic drugs at 12 months or greater follow-up were included. In the PVI plus FIRM group, all public studies reporting a single procedure off antiarrhythmic drug success rate with at least one year follow-up were identified.                                 Meta-analytic estimates were derived, using the DerSimonian and Laird Random-effects Models, and pooled estimates of success rates. Statistical heterogeneity was assessed using the Cochran Q test and I-square. Study quality was assessed with the Newcastle-Ottawa Scale.                                 15 trials were included, 10 with PVI plus FIRM, with 511 patients, non-randomized perspective design, and 5 pulmonary vein isolation-only trials, consisting of 295 patients, all randomized.                                 All patients in the pulmonary vein only trials had 100% non paroxysmal atrial fibrillation, except for one study, and no prior ablations. About 24% of the PVI plus FIRM patients had paroxysmal atrial fibrillation.                                 After 15.9 months of follow-up, the off antiarrhythmic drug pooled success was 50% with FIRM plus PVI, compared to 58% in the PVI alone. The difference in the effect size between the groups was not statistically significant. No significant heterogeneity was observed in this meta-analysis.                                 The authors concluded that the overall pooled estimate did not show any therapeutic benefit of PVI FIRM over PVI alone.                                 That's it for this month, but keep listening. Suraj Kapa will be surfing all journals for the latest topics of interest in our field. Remember to download the podcast On The Beat. Take it away, Suraj. Suraj Kapa:          Thank you, Paul, and welcome back to “On The Beat”. Again, my name is Suraj Kapa and I'm here to review with you articles across the cardiac electrophysiology literature that were particularly hard hitting in the month of February.                                 To start, we review the area of atrial fibrillation, focusing on anticoagulation. Reviewing an article published in this past month's issue of the Journal of the American Heart Association, by Steinberg et al., entitled Frequency and Outcomes of Reduced Dose Non-Vitamin K Antagonist Anticoagulants, results from ORBIT AF II. The ORBIT AF II registry, also called the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, is a prospective national observational registry of AF patients.                                 The author sought to describe the frequency, appropriateness, and outcomes of patients prescribed reduced doses of NOACs in the community practice. They reviewed the records of almost 8,000 patients receiving NOACs and noted that the vast majority, nearly 84%, received a standard dose of NOACs, consistent with the U.S. FDA labeling. While only 16% received a reduced dose, only 43% of these were consistent with labeling instructions. Those who received reduced dose NOACs inappropriately more often tended to be younger and have, interestingly, lower overall bleeding risks scores.                                 Furthermore, compared with those appropriately receiving dosing, patients receiving inappropriately reduced dose NOACs had a higher unadjusted rates of thromboembolic events and death.                                 These data are important to understand, in that, discussion with patients, that inappropriate reduction of NOACs does not necessarily offer appropriate protection against long-term risk of thromboembolic events. Thus, close attention must be paid to consideration of the use cases and instructions for use.                                 While the registry cannot get into the details of why the dose was reduced in the spectrum of patients, it does highlight the fact that this continues to be a problem in general practice.                                 Further data is needed to understand what leads to inappropriate dose reduction, which could include factors such as patient preference, or physician education.                                 Staying within the realm of anticoagulation and understanding individual needs, we next review an article published in this past month's issue of Circulation, by Nielsen et al., entitled Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation. Should we use a CHA2DS2-VA score rather than CHA2DS2-VASc? In this review, the authors sought to evaluate whether female sex is truly an overall risk factor, as opposed to a risk modifier.                                 Using three nationwide registries, they identified patients with nonvalvular atrial fibrillation between 1997 and 2015, and they calculated two sets of scores. The first score, they termed a CHA2DS2-VA score, calculated for men and women with follow-up of one year in the Danish National Patient Registry. They wanted to calculate the risk based on this pseudo-value method. They then reviewed female sex as a prognostic factor by inclusion as an interaction term on the CHA2DS2-VA score, to calculate overall thromboembolic risk.                                 Amongst over 200,000 patients with atrial fibrillation, almost half of whom are women, they noted that the mean CHA2DS2-VA score, where sex is excluded, was a tad higher in women than men, namely 2.7 vs. 2.3. However, women had an overall higher one year thromboembolic rate of 7.3 vs. 5.7 per 100 person-years. Interestingly, with a CHA2DS2-VA score of zero, the absolute risk of thromboembolism was equal amongst men and women, around .5%. Once overall points increased above one, however, women exhibited a higher stroke risk. This interaction was statistically significant.                                 Thus, the authors indicated that female sex is a risk modifier for stroke in patients with atrial fibrillation, rather than a risk factor. The terminology is important to consider. Essentially, what they are noting is that at the lower risk level, female sex, in and of itself, is not something that necessarily puts somebody in the higher risk cohorts. Instead, at higher risk levels, because of other factors, a woman may have a higher overall risk of stroke than men. Thus, stroke risk is accentuated in women, who would have been eligible for oral anticoagulating treatment anyway, on the basis of a CHADS score above one.                                 These data highlight the importance of thinking about the fact that at the lower risk score level, female sex alone might not be sufficient to say that a patient has reached the CHA2DS2-VASc score of one and above. But, really, you need an overall CHA2DS2-VA score, or a risk score, inclusive of at least two other risk factors to indicate that now, being a female is going to modify the risk and further accentuate it.                                 Now, one thing to note is, these data are very consistent with the guidelines. The European guidelines indicates that female sex alone, which in the CHA2DS2-VASc score would confer a risk score of one, should not, by itself, construe the need to put somebody on anticoagulation.                                 However, it's important to highlight that these data show that at a CHA2DS2-VASc score of one in females, they should really be construed as equivalent to a CHA2DS2-VASc score of zero in men.                                 Using the CHA2DS2-VA score, where sex is excluded, but considering that women overall have a higher incidence of stroke at any given CHA2DS2-VA level above one, will help better counsel women about the importance of being on anticoagulants.                                 The next article we review relates to long-term risk related to atrial fibrillation, published in February's issue of Heart Rhythm, by Nishtala et al., entitled Atrial Fibrillation and Cognitive Decline in the Framingham Heart Study. While there's much out there about the potential long-term role of cognitive decline in atrial fibrillation patients, longitudinal research investigating the relationship is relatively sparse. Thus, the authors sought to investigate the association between atrial fibrillation and cognitive performance, cross-sectionally and longitudinally.                                 They chose patients within the Framingham study who are dementia and stroke-free at the time of baseline neuropsychological assessments. They evaluated atrial fibrillation status as a two level variable, namely prevalent atrial fibrillation vs. no atrial fibrillation in cross-sectional analyses. And they also separated into prevalent atrial fibrillation at baseline, interim development of atrial fibrillation, and those who didn't develop any atrial fibrillation in longitudinal analysis.                                 They studied 2,682 participants in the Framingham Heart study, including original and offspring cohorts. They noted that a baseline of about 4% had diagnosed atrial fibrillation. Prevalent AF was noted to be significantly associated with poorer attention. Interestingly, sex differences were noted, with men performing worse on test of abstract reasoning and executive function than women.                                 They noted that prevalent atrial fibrillation was significantly associated with the longitudinal decline in executive function, in both the original cohorts, as well as interim atrial fibrillation being significantly associated with longitudinal decline in executive function of the offspring cohorts. Thus, they noted that atrial fibrillation is associated with a profile of long-term change in cognitive function.                                 The importance of these data are to further highlight the potential contribution of atrial fibrillation to cognitive decline. While the exact mechanisms remain to be fully elucidated, the question of how to get ahead of the cognitive decline associated with atrial fibrillation is further put out by these data.                                 Whether the relationship between atrial fibrillation and cognitive decline is due to recurrent thromboembolic events vs. the therapies used vs. other factors such as humid anatomic factors resulting in poor brain perfusion, are relatively unclear.                                 Certainly it is also possible that atrial fibrillation simply reflects a process associated with other factors that might lead to cognitive decline. However, again, further mechanistic studies and potential treatment interventions to mitigate the risk of cognitive decline are still needed.                                 Speaking of this, we next review a paper published in the European Heart Journal this past month, by Friberg and Rosenqvist, entitled Less Dementia with Oral Anticoagulation in Atrial Fibrillation.                                 Speaking of treatments to avoid long-term cognitive decline, the authors sought to evaluate if oral anticoagulant treatment might offer protection against long-term dementia risk in atrial fibrillation.                                 These retrospective registry studies of patients with the hospital diagnoses of atrial fibrillation and no prior diagnosis of dementia in Sweden, including patients between 2006 and 2014. The study included a total of 444,106 patients over 1.5 million years. They noted that patients who were on anticoagulant treatment at baseline were associated with a 29% lower risk of dementia than patients without anticoagulant treatments. Thus, there is an overall 48% lower risk on treatments with the appropriate anticoagulation. There is no difference on whether Warfarin or the newer oral anticoagulants were used.                                 Thus, the authors concluded that the risk of dementia is higher without oral anticoagulant treatment in patients with atrial fibrillation, suggesting that early initiation of anticoagulant treatment in patients with atrial fibrillation could be of value to preserve long-term cognitive function.                                 This relates directly back to the previous paper, which focused more on the epidemiologic risk, while this paper focuses on elements that might construe mechanism or treatment options.                                 Many authors have concluded the incredible importance of early recognition of the need for anticoagulant initiation in patients with atrial fibrillation. While the exact mechanism of cognitive decline and dementia in atrial fibrillation remains to be completely elucidated, certainly recurrent thromboembolic events that might be relatively silent as they occur, but result in a long-term cumulative risk might be helped by placing patients on anticoagulants.                                 This becomes another reason to counsel patients on the importance of long-term anticoagulant therapy. Certainly, the limitations of these studies, however, are the retrospective nature and the fact that there might be some subtle differences that may not be otherwise able to be construed from retrospective registry data regarding the relative role of anticoagulants in truly protecting against long-term cognitive decline. However, the data are certainly provocative.                                 Continuing within realm and discussing outcomes associated atrial fibrillation, we next review an article by Leung et al., entitled The Impact of Atrial Fibrillation Clinical Subtype on Mortality, published in JACC: Clinical Electrophysiology this past month.                                 The author sought to investigate the prognostic implications of a subtype of atrial fibrillation, paroxysmal or persistent, on long-term prognosis. They sought to evaluate differences in mortality between paroxysmal or persistent atrial fibrillation amongst 1,773 patients. They adjusted for comorbid diseases associated with atrial fibrillation, as well as CHA2DS2-VASc score. In the study, a total of about 1,005 patients or about 57% had persistent atrial fibrillation. Over the follow-up period, about 10% of those with paroxysmal atrial fibrillation and 17% of those with persistent atrial fibrillation died.                                 They noted that persistent atrial fibrillation, after correcting for other comorbidities, was independently associated with worse survival. Thus, they concluded that persistent atrial fibrillation is independently associated with increased mortality in the long term.                                 These data are relevant in that they highlight that persistent atrial fibrillation in its nature might construe an overall higher risk cohort. It remains to be fully understood what are the true mechanistic differences between persistent and paroxysmal atrial fibrillation. Overall, however, the community grossly agrees that persistent atrial fibrillation likely suggests a higher degree of atrial myopathy. If we believe this, then it is reasonable to believe that the risk associated with this specific form of atrial fibrillation might result in higher long-term harm.                                 Of course, these data are subject to the same limitations of all retrospective data. Namely, these persistent atrial fibrillation patients might have received different therapies or been more sick to start with that cannot be construed by comorbidities alone.                                 Furthermore, these data do not necessarily get to the point of whether treating atrial fibrillation in the persistent patient more aggressively necessarily reduces the risk equivalent to that of paroxysmal patients. Thus, further understanding is needed to understand how to use these data to reduce this mortality difference.                                 Continuing within the realm of epidemiology of atrial fibrillation, we next review an article published in this past month's issue of Circulation, by Mandalenakis et al., entitled Atrial Fibrillation Burden in Young Patients with Congenital Heart Disease. It is assumed that patients with congenital heart disease are vulnerable to atrial fibrillation because of multiple factors. These include residual shunts, hemodynamic issues, atrial scars from previous heart surgery, valvulopathy and other factors.                                 However, there's limited data on the overall risk of developing atrial fibrillation and complications associated with it, especially in children and young adults with congenital heart disease. Furthermore, these children and young adults with congenital heart disease have never been compared with overall risk and control subjects.                                 The authors use the Swedish Patient and Cause of Death Registries to identify all patients with diagnoses of congenital heart disease born from 1970 to 1993. They then matched these patients with control subjects from the Total Population Register in Sweden. They noted amongst almost 22,000 patients with congenital heart disease and almost 220,000 matched control subjects that 654 patients amongst the congenital heart disease cohort developed atrial fibrillation, while only 328 amongst the larger control group developed atrial fibrillation. The mean follow-up overall was 27 years.                                 They noted the risk of developing atrial fibrillation was almost 22 times higher amongst patients with congenital heart disease than control subjects. They noted the highest risk with a hazard ratio of over 84 was noted in patients with conotruncal defects. Furthermore, at the age of 42 years, over 8% of patients with congenital heart disease had a recorded diagnosis of atrial fibrillation.                                 Interestingly, heart failure was a particularly important complication in patients with congenital heart disease and atrial fibrillation, with over 10% of patients developing atrial fibrillation and [inaudible 00:38:20] congenital heart disease developing a diagnosis of heart failure as well.                                 These data are important in that they help in counseling the importance of close follow-up of patients with congenital heart disease and their long-term risk of other complications. Even if patients might be perceivably well managed, incident atrial fibrillation might increase risk of stroke in these patients. It is further important to note that many of these patients cannot be evaluated according to traditional risk or evaluations. Thus, it is important to consider whether or not a patient should be treated with anticoagulation once they develop atrial fibrillation.                                 The high risk of overall atrial fibrillation incidents, particularly in patients with more complex congenital defects, needs to be taken into consideration when advising on the frequency of follow-up.                                 It is important to further note that we must think of this overall risk as the minimum possible risk, namely, counseling a congenital heart disease patient that up to one in ten of them may develop atrial fibrillation by the age of 42 years, is likely the minimum amount. The reason for this is many patients, due to either lack of follow-up or lack of sufficient monitoring, and the asymptomatic nature of atrial fibrillation in many patients might have not been diagnosed.                                 Implications or treatments remain to be seen, and whether or not there are methods to reduce the overall risk of atrial fibrillation is unclear. However, engaging congenital heart disease experts and advising patients, especially at younger ages, on the importance of close electrocardiographic monitoring for a potential atrial fibrillation risk is critical.                                 Next within the realm of atrial fibrillation, we switch to the topic of ablation. And review an article by Pallisgaard et al., published in this last month's issue of European Heart Journal, entitled Temporal Trends in Atrial Fibrillation Recurrence Rates After Ablation, between 2005 and 2014: a nationwide Danish cohort study.                                 Ablation has been increasingly used as a rhythm control strategy for patients with atrial fibrillation. Over this time, we have all noted evolution in both the experience and the techniques used. Thus, the authors sought to evaluate whether recurrence rate of atrial fibrillation has changed over the last decade. They included all patients with first-time AF ablation done between 2005 and 2014 in Denmark. They then evaluated recurrent atrial fibrillation based on a one year follow-up. They included a total of 5,425 patients undergoing first-time ablation.                                 They noted, interestingly, that the patient median age increased over time, and the median AF duration prior to ablation decreased over time. However, the rates of recurrent atrial fibrillation decreased from 45% in 2005 to 31% in the more recent years of 2013, 2014. With the relative risk of recurrent atrial fibrillation almost being cut in half.                                 They noted that female gender, hypertension, atrial fibrillation duration more than two years, and cardioversion with one year prior to ablation were all associated with an increased risk of recurrent atrial fibrillation, regardless of year.                                 These data, again, are retrospective and thus must be taken in the context of that consideration. However, they highlight that it is possible either our selection of appropriate patients for atrial fibrillation ablation or our techniques have improved overall success.                                 The fact that atrial fibrillation ablation is still a relatively young field, with evolving approaches and evolving techniques, needs to be taken into consideration when advising patients on success rates. Using data from many years prior to informed discussion today is fraught with potential error, especially as our catheter design and mapping system use and understanding of appropriate lesion set changes.                                 Of course, some criticism is required as well. While the patients included were relatively older in more recent years, the total AF duration prior to ablation decreased over the years. This suggests that patients are being ablated earlier than they were in the early days of atrial fibrillation ablation.                                 There is some data out there to suggest that earlier ablation for atrial fibrillation might result in a lower long-term recurrence rate. Thus, this might account for some of the difference. However, it is unlikely that it accounts for all of it, given the degree of reduction in overall risk of occurrence.                                 Staying within the trend of talking about changes in techniques for atrial fibrillation ablation, we next review an article published in this past month's issue of Heart Rhythm, by Conti et al., entitled Contact Force Sensing for Ablation of Persistent Atrial Fibrillation: A Randomized, Multicenter Trial. Contact force sensing is one of the newer techniques being used to optimize the success rates for atrial fibrillation ablation. It is generally felt that understanding when one is in contact will optimize atrial fibrillation ablation outcomes by ensuring the physician knows each time they are in contact, and also potentially reducing complications by avoiding excessive contact.                                 Thus, the authors designed the TOUCH AF trial to compare contact force sensing-guided ablation vs. contact force sensing-blinded ablation. They included a total of 128 patients undergoing first-time ablation for persistent atrial fibrillation, and thus randomized them to a situation where the operator was aware of the contact force vs. blinded to the contact force. While the force data was hidden in the blinded cohort, it was still recorded on the backend.                                 In all patients, wide antral pulmonary vein isolation plus a roof line was performed, and patients were followed at 3, 6, 9, and 12 months, with clinical visits, ECGs, and 48-hour Holter monitoring.                                 The primary endpoint was cumulative radio frequency time for procedures, and atrial arrhythmia is greater than 30 seconds after three months is considered a recurrence.                                 They noted that average force was higher in the contact force-guided arm than contact force-blinded arm, though not statistically significant, with an average of 12 grams in the latter and 14 grams in the former.                                 Interestingly, the total time of ablation did not differ between the two groups. Furthermore, there was no difference in the single procedure freedom from atrial arrhythmia, computing to about 60% in the contact force-guided arm vs. the 63% in the contact force-blinded arm. They did notice, however, that lesions with associated gaps were associated with significantly less force and less force-time integral.                                 The authors concluded from this, the contact force-guided ablation did not result in significant decrease in total radio frequency time or 12-month outcomes in terms of freedom from atrial arrhythmias.                                 These data are important to help guide us in terms of thinking about how the tools we use, as they change, actually alter outcomes. Sometimes we may perceive benefits based on logical thinking that's knowing more about what is happening when we are performing a procedure should optimize that procedure. However, this is not necessarily always the case, and thus highlights the importance of randomized trials to directly compare different situations, such as awareness of contact force vs. lack of awareness of contact force.                                 The relevance of these particular articles is that when we compare catheters with different designs, it does not necessarily highlight the importance of the force number itself. Namely, comparing a contact force catheter vs. non-contact force catheter implicates use of essentially two completely different catheters. To understand the incremental utility of force in making decisions, it is important to consider the same catheter, but simply with awareness or lack of awareness of the actual force number.                                 One of the limitations, however, is that individuals who might have been trained on using the same force sensing catheter might have some degree of tactile feedback and understanding of the amount of force being applied to the tip of the catheter, based on having been repeatedly exposed to contact force numbers during use of said catheter. Thus, there might be a difference in being blinded to contact force in early stage operators than in later stage operators who might have been trained based on repeated feedback.                                 Thus, it's difficult to conclude, necessarily, that contact force is not offering mental benefit. In fact, there's a fair chance that it does. However, offering a skeptical viewpoint to help guide the importance of continually evolving technology in actually improving outcomes is important.                                 Finally, within the realm of atrial fibrillation, we review an article published by Pathik et al., in this past month's issue of Heart Rhythm, entitled Absence of Rotational Activity Detected Using 2-Dimensional Phase Mapping and the Corresponding 3-Dimensional Phase Maps in Human Persistent Atrial Fibrillation.                                 Current clinically used phase mapping systems involve 2-dimensional maps. However, this process may affect accurate detection of rotors. The authors sought to develop 3-dimensional phase mapping technique that uses a 3D location of the same basket electrodes that are used to create the currently available 2-dimensional maps. Specifically, they wanted to determine whether the rotors detected in 2D phase maps were present in the corresponding time segments and anatomical locations in 3D phase maps.                                 They used one minute left atrial atrial fibrillation recordings obtained in 14 patients, using the basket catheter, and analyzed them offline, using the same phase values, based on 2-dimensional vs. 3-dimensional representations.                                 They noted rotors in 3.3% using 2D phase mapping, 9 to 14 patients demonstrated about 10 transient rotors, with a mean rotor duration of about 1.1 seconds. They noted none of the 10 rotors, however, were seen at the corresponding time segments and anatomical locations in 3D phase maps. When looking at 3D phases maps, 4 of the 10 corresponded with single wavefronts, 2 of 10 corresponded with simultaneous wavefronts, 1 of 10 corresponded with disorganized activity, and 3 of 10 had no coverage by the basket catheter at the corresponding 3D anatomical locations.                                 These data are important, in that they highlight the importance of when we consider reflecting 2-dimensional systems in a 3-dimensional world of atrial fibrillation. The role of ablating rotors is still in question. However, it is still an important question, and it requires continued study. The best way of identifying a rotor, knowing a rotor is a rotor, and understanding where the rotor is, are going to be critical to further evaluating whether actual ablation of these rotors has any relevance to long-term atrial fibrillation ablation.                                 The truth is, that we need to be sure that we are properly identifying all the rotors in order to help guide whether or not we are actually being successful in ablating atrial fibrillation. The importance of the study is in reflecting whether 2-dimensional representations of the 3-dimensional geometry is sufficient to reflect what is actually happening in that 3-dimensional geometry. These authors suggest that it is not.                                 One of the limitations, however, might be that when we wrap a 2-dimensional framework into 3 dimensions and perform additional post-processing, this might result in some degree of attenuation of the data. However, it does highlight the importance for continued rigorous evaluation of current approaches to phase mapping.                                 Several articles have been published in recent months as well, about different single processing techniques to evaluate whether or not a rotor is, in fact, a rotor and to help optimize identification of them.                                 The jury is still out on whether or not targeted ablation of rotors will, in fact, improve overall long-term atrial fibrillation ablation outcomes. The limitations might not necessarily be that rotors are not an appropriate target, but that we just don't understand entirely where rotors are, based on limited single processing options, or based on limitations of anatomical localization.                                 Next, delving into the realm of ablation at large, we review an article by Iwasawa et al., published in this past month's issue of Europace, entitled Trans Cranial Measurement of Cerebral Microembolic Signals During Left-Sided Catheter Ablation with the Use of Different Approaches - the Potential Microembolic Risk of a Transseptal Approach.                                 The authors note the importance of considering microemolization in subclinical brain damage during catheter ablation procedures. They evaluated microembolic signals detected by transcranial Doppler during ablation of supraventricular or ventricular arrhythmias with the use of either a transseptal or a retrograde approach.                                 The study set was small, only including 36 patients who underwent catheter ablation. They noted in about 11 patients left-sided ablation was done with transaortic approach, and in 9 patients a transseptal approach was used. The other 16 patients were not included, as they only had right-sided ablation.                                 The total amount of microembolic signature, based on transcranial Doppler were counted throughout the procedure and then analyzed offline. There is no significant difference in number of radio frequency applications, total energy delivery time, total application of energy, or total procedure time between the different groups. However, they did note that the mean total number of microembolic signals was highest in those undergoing transseptal approach to left-sided ablation. It was significantly lower in those having retrograde aortic approach, and lowest in those having right-sided only ablation.                                 Interestingly, many of the microembolic signals were detected during the transseptal puncture period, and then during the remainder of the procedure there was relatively even distribution of emboli formation. A frequency analysis suggested that the vast majority of microembolic signals are gaseous, in particularly Group 1 and Group 3, though only 91% in Group 2. No neurological impairment was observed in any of the patients after the procedure.                                 Recently, there's been a lot of focus on the potential long-term risk of cognitive impairments due to microembolic events in the setting of ablation. At least one recent paper in ventricular arrhythmias and several recent papers in atrial fibrillation ablation have suggested a fairly high risk of incidence cerebral emboli noted on MRI post ablation. While these results do not necessarily get at MRI lesions, they do suggest microembolic events. And what is most interesting, they look at microembolic events that occur throughout the entire ablation period with different approaches.                                 Interestingly, there is a massive spike in overall microembolic signals during the transseptal puncture period, and relatively even distribution throughout ablation, irrespective of application of radio frequency or not. Furthermore, while nearly all microembolic signals are gaseous, based on frequency analysis, with retroaortic approach or in those having right-sided only ablation, significantly less seem to be due to gaseous events in those having a transseptal approach.                                 It is known that there's possible damage to the internal dilation system when exposing it to transseptal needles or wires. Thus, one has to wonder whether some of the embolization could be from material associated with the actual transseptal puncture, either from portions of the punctured septum itself, or perhaps from the plastic material that which is being pushed transseptally.                                 These data still need to be considered and we have yet to see what the long-term applications of these kinds of findings are. It may be possible that while transseptal approach seems to offer more instant microembolic signals, if the long-term risk is no different, does it really matter?                                 However, these findings are provocative in the sense that they highlight potential significant differences and the risk of silent cerebral damage, based on the approach we use to ablation.                                 Changing gears, we next focus on the role of devices. And the first paper review is in the last month issue of JACC: Heart Failure, by Gierula et al., entitled Rate Response Programming Tailored to the Force Frequency Relationship Improves Exercise Tolerance in Chronic Heart Failure.                                 The authors sought to examine whether the heart rate at which the force frequency relationship slope peaks can be used to tailor heart rate response in chronic heart failure patients with cardiac pacemakers, and to see whether this favorably influences exercise capacity.                                 They performed an observational study in both congestive heart failure and healthy subjects with pacemaker devices. They then evaluated in a double-blind, randomized, controlled crossover study, the effects of tailored pacemaker rate response programming on the basis of a calculation of force frequency relationship based on critical heart rate, peak contractility, and the FFR slope.                                 They enrolled a total of 90 patients with congestive heart failure into the observational study cohorts, and 15 control subjects with normal LLV function. A total of 52 patients took part in the crossover study. They noted that those who had rate response settings limiting heart rate rise to below the critical heart rate were associated with greater exercise time and higher peak oxygen consumption, suggesting the tailored rate response program can offer significant benefit, particularly in congestive heart failure patients.                                 The importance of this trial is in that it highlights the importance of thoughtful decision-making in programming devices, and that group decision-making involving exercise physiologists, alongside pacemaker programming, and involving our congestive heart failure specialists might be the most critical in optimizing the approach to programming.                                 It might be that more aggressive measures are needed in congestive heart failure patients to decide on what optimal programming is, than it is in otherwise normal patients.                                 Staying within the realm of devices, we next focus on a publication by Sanders et al., published in this past month's issue of JACC: Clinical Electrophysiology, entitled Increased Hospitalizations and Overall Healthcare Utilization in Patients Receiving Implantable Cardioverter-Defibrillator Shocks Compared With Antitachycardia Pacing.                                 The authors sought to evaluate the effect of different therapies and healthcare utilization in a large patient cohorts. Specifically comparing antitachycardia pacing with high voltage shocks. They used the PROVIDE registry, which is a prospective study of patients receiving ICDs for primary prevention in 97 U.S. centers. They categorized these patients by type of therapy delivered, namely no therapy, ATP only, or at least one shock. They then adjudicated all ICD therapies, hospitalizations, and deaths.                                 Of the 1,670 patients included, there was a total follow-up of over 18 months. The vast majority, 1,316 received no therapy, 152 had ATP only, and 202 received at least one shock.                                 They noted that patients receiving no therapy and those receiving only ATP had a lower cumulative hospitalization rate and had a lower risk of death or hospitalization. The cost of hospitalization was known to be significantly higher for those receiving at least one shock than for those receiving only ATP therapy.                                 They noted no difference in outcomes or cost between patients receiving only ATP and those without therapy. Thus, the authors concluded that those receiving no therapy or those receiving only ATP therapy had similar outcomes, and had significantly reduced hospitalizations, mortality, and costs compared to those who received at least one high voltage shock.                                 The relevant findings from this study is similar to prior studies that suggest that any shock over follow-up is associated with potential increase in long-term mortality. The difficulty in assessing this, however, is the fact that it might be that those who have VT that can be appropriately ATP terminated, might be at a somewhat lower risk than those who need to be shocked to get out of their VT. Thus, the presumption of needing a shock to restore normal rhythm might suggest a higher risk cohort, it cannot be gleaned from traditional evaluation of morbid risk factors.                                 This is why the importance of considering how devices are programmed and whether or not a patient who has received shocks can be reprogrammed to offer ATP only therapy to terminate those same VTs, needs to be taken into consideration. How to best tailor this therapy, however, is still remaining to be determined, though more and more clinical trials are coming out to suggest in terms of optimal overall population-wide programming for devices.                                 Staying with the realm of devices, we next review an article by Koyak et al., in this past month's issue of Europace, entitled Cardiac Resynchronization Therapy in Adults with Congenital Heart Disease.                                 Heart failure is one of the leading causes of morbidity and mortality amongst patients with congenital heart disease. But there's limited experience in the role of cardiac resynchronization therapy amongst these patients. Thus, the authors sought to evaluate the efficacy of CRT in adults with congenital heart disease.                                 They performed a retrospective study on a limited number of 48 adults with congenital heart disease who received CRT, amongst four tertiary referral centers. They have defined responders as those who showed improvement in NYHA functional class or improvement in systemic ventricular ejection fraction. The median age at CRT implant was 47 years, with 77% being male. There was a variety of syndromes included.                                 They noted that the majority of patients, nearly 77%, responded to CRT, either by definition of improvement of NYHA functional class, or systemic ventricular function, with a total of 11 non-responders.                                 They noted that CRT was accomplished with a success rate comparable to those with acquired heart disease. However, the anatomy is much more complex and those technical challenges in achieving success o

  Paul Wang:         Welcome to the monthly podcast On the Beat for Circulation, Arrhythmia, and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field.                                 In our first study, Boris Schmidt and associates studied 134 patients with persistent atrial fibrillation, randomized to laser balloon or wide area circumferential pulmonary vein isolation using irrigated radiofrequency current ablation and 3D mapping.                                 They found that 71% of patients in the laser balloon group had freedom from atrial fibrillation between 90 and 365 days after a single ablation, similar to 69% of patients in the radiofrequency group, p=0.40. In the laser balloon group, one patient developed stroke, one had false aneurysm and one had phrenic nerve palsy. In the radiofrequency group, two patients developed a false aneurysm and one patient needed surgical repair. Procedure and fluoroscopy times were similar between the two groups. The authors concluded that the two methods were associated with similar efficacy in patients with persistent atrial fibrillation.                                 In the next study, Kairav Vakil and associates examined the success of VT ablation in elderly patients who were part of the International VT Center Collaborative Study Group Registry. Of the 2,049 patients in the registry, 33% or 681 were greater than or equal to 70 years of age with a mean age of 75 years.                                 Compared to patients less than 70 years, patients 70 years or greater had higher in-hospital, 4.4% versus 2.3%, p=0.1 mortality, and also a higher one year mortality, 15% versus 11%, p=0.002. But they had a similar instance of VT recurrence, 26% versus 25% and a similar time to recurrence, 280 versus 289 days.                                 The authors concluded that VT ablation in elderly is feasible with reasonable safety and modestly higher in-hospital and one year mortality with similar rates of VT recurrence at a one year compared to younger patients.                                 In the next study, Angel Ferrero-de Loma-Osorio and associates studied the optimal dosage of cryotherapy using cryoballoon ablation of pulmonary veins. The study the prospective, randomized, multicenter, non-inferiority study including 140 patients with paroxysmal atrial fibrillation which was refractory to antirrhythmic drugs.                                 Patients were randomly assigned to a conventional strategy group of 180 seconds cryoablation applications per vein with a bonus freeze 70 patients or a shorter time application protocol with one application that lasted the time required for a electrical time to effect plus 60 seconds and a 120 second freeze bonus, 70 patients.                                 At one year followup there was no difference in freedom from atrial fibrillation 79.4% of the control group versus 78.3% in the study group, p=0.87. The time to effect was detected in 72% of the veins. The study and control group had similar mean number of applications per patient, 9.6 versus 9.9. compared to controls the study group had a significantly shorter cryotherapy time, 28.3 versus 19.4 minutes, p80 or >90, especially when one refers to the appropriate use criteria where appropriateness was reclassified based on what the age range was and what the indication was from a primary prevention defibrillator. Further study is need to understand whether we really should apply an age cutoff to the benefit of ICDs but it is an important thing to consider when counseling patients, especially in light of evolving evidence in this area.                                 Still staying in the realm of heart failure but now going to more basic electrophysiology, we review a paper published in Circulation this past month by Cho et al., entitled Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.                                 Increasingly, heart failure with preserved ejection fraction is being diagnosed to the point where it is now approximately half of all diagnosed heart failure with incidences that continue to increase nevertheless. One of the leading causes of mortality in heart failure with preserved ejection fraction is sudden death but the underlying mechanisms for this is less clear.                                 Thus in a rat model, Cho et al., sought to evaluate why heart failure with preserved ejection fraction might result in an increase risk of sudden death. They exposed salt sensitive rats to a high salt diet and evaluated the effect on systolic and diastolic function. After verifying, some rats that suffered from HFpEF at this point versus control rats, they underwent programmed electrical stimulation and they measured corrected QT interval from surface ECG as well. Furthermore they did optical mapping, whole-cell patch clamping and quantitative polymerase chain reaction and Western blotting to evaluate ion channel expression.                                 They noted that 31 of 38 rats exposed to a high salt diet demonstrated diastolic dysfunction and preserved ejection fraction along with signs of heart failure. There was an increased susceptibility to ventricular arrhythmias amongst these particular rats when compared to controls. They also noted that the corrected QT interval was significantly longer. Interestingly optical mapping showed that these rats had prolonged action potentials and multiple reentry circuits during induced ventricular arrhythmias. Furthermore there was confirmed a delay of repolarization based on patch clamping with a downregulation of transient outward potassium currents or ITO. Finally they noted that there was a downregulation of IK1 as well as IKR.                                 Thus they felt that the susceptibility to ventricular arrhythmias was indeed markedly increased, at least in a rat model of HFpEF. These could be caused by QT prolongation, which is associated with delayed repolarization from downregulation of potassium currents and also associated multiple reentry circuits which can mediate ventricular arrhythmia. These findings are significant in that they highlight both potential targets for sudden death risk in the setting of HFpEF as well as potential targets for treatments that might prevent ventricular arrhythmias in the long term.                                 Staying within the realm of ventricular arrhythmias, we next review an article by Do et al., published in the Journal of the American Heart Association this past month, entitled Thoracic Epidural Anesthesia Can Be Effective for the Short‐Term Management of Ventricular Tachycardia Storm.                                 Similar to the earlier discussed article, of optogenetic stimulation of left stellate ganglion, even short term management options for VT storm are important. Some inject lidocaine or bupivacaine into the left stellate ganglion or into both stellate ganglia in order to get control. However, depending on comfort level, the utility of this may be variable at different institutions.                                 Thus, novel therapies aimed at modulating the autonomic nervous system that might be available at other institutions such as thoracic epidural anesthesia are important to consider. The group sought to evaluate via multicenter experience what the effect on VT storm was with thoracic epidural anesthesia.                                 They noted amongst 11 patients reviewed between July 2005 and March 2016 that the majority who underwent thoracic epidural anesthesia had incessant VT with a minority of them being polymorphic VT. Furthermore almost half of them had nonischemic cardiomyopathies. Almost half of the patients had a complete response to thoracic epidural anesthesia where the VT became quiescent. And one patient had a partial response.                                 Thus, they suggested that thoracic epidural anesthesia may be effective and should be considered as a therapeutic option in patients with VT storm, especially those with incessant VT, who are refractory to initial management. They also noted clinically that improvement in VT burden associated with deep sedation may suggest a higher likelihood of responding to thoracic epidural anesthesia. For a clinical electrophysiologist especially in community hospitals where rapid utilization of ablation may not be possible or other advanced methods of autonomic modulation might not be feasible, options such as thoracic epidural anesthesia are important to be considered. They exist in an armament that includes intravenous drugs, left stellate ganglion injections, general anesthesia and use of IV beta blockers. These findings are highly suggestive and the fact that certain clinical characteristics might suggest those that are more likely to benefit might just to clinicians exposed to a patient of VT storm what the next step should be.                                 Changing gears a little bit we will now review an article by Rafaat in the Journal of the American Heart Association entitled Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter‐Free Ablation of Cardiac Arrhythmias.                                 The group sought to demonstrate using a linear accelerator based stereotactic radiosurgery system whether or not atrioventricular node ablation could be safely performed with minimal damage to surrounding structures. They used the linear accelerator to apply energy in a pig model after implantation of a pacemaker using a CT scan to guide therapy. They also performed pathologic evaluation of the region of the AV node and the surrounding tissues. They found that all animals included had disturbances of AV conduction with progressive transition into complete heart block. There was no damage to the surrounding myocardium and all pigs had preserved systolic function echocardiography.                                 Thus they suggested that catheter free radioablation using this approach might be feasible in an intact swine. These findings are important because they build on other studies done by groups at other centers suggesting that noninvasive linear accelerator based therapies either using stereotactic radiosurgery with existing technologies, proton beams, carbon beams or other approaches, might offer feasible methodologies for noninvasive treatment for cardiac arrhythmias. Further study is indeed needed to validate what the effect on surrounding tissues actually is.                                 Next we will review an article published by Williamson et al., in JACC Clinical Electrophysiology this past month entitled Real-World Evaluation of Magnetic Resonance Imaging in Patients With a Magnetic Resonance Imaging Conditional Pacemaker System.                                 Results of four year prospective followup in over 2,600 patients, while MRI conditional pacemakers are more increasingly used, long term longevity as well as effects of multiple MRI scans in terms of MRI functioning the devices is unclear. Thus, the study was sought to be a large scale, real world evaluation of MRI in patients with MRI conditional pacemakers. They included over 2,600 patients in multiple centers and all these patients had a SureScan pacing system. They noted that there were no MRI related complications occurring during or after the MRI, meeting the primary objective. In fact, almost a third of the patients underwent two or more scans and even then there was no cumulative increase in problems in these patients. The pacing capture thresholds stayed stable throughout all patients.                                 Thus this report constituted the largest longitudinal MRI experience in patients implanted with an MRI conditional device. The importance of this is to be able to highlight to patients that in fact even multiple MRIs despite having a device in place is safe. There is an increasing body of data that suggests that however, MRIs might be safe in a controlled setting, even in patients with legacy pacemakers. Whether MR conditional pacemakers actually offer incremental safety over legacy pacemakers however, is less clear and will likely require randomized trials of a large scale given the low number of events to really come to a conclusion. However, in most centers where it's not possible to do MRIs in legacy pacemakers, this offers some level of certainty that patients will likely be safe even undergoing multiple MRIs in a setting of having chronic pacemakers that are MRI conditionally safe.                                 Staying within the realm of looking at large multicenter experiences, we review an article by Hosseini et al., entitled Catheter Ablation for Cardiac Arrhythmias, Utilization and In-Hospital Complications, 2000 to 2013, published in JACC Clinical Electrophysiology this past month.                                 In this study, Hosseini et al., sought to investigate the overall utilization and in-hospital complications associated with catheter ablation in of all types in the United States between 2000 and 2013 using the National Inpatient Sample and Nationwide Inpatient Samples. They included all patients 18 years of age and older who underwent inpatient catheter ablation over this time period.                                 They estimated total a total of almost 520,000 inpatient ablations performed in this time period with a median age of 62 years amongst patients. Interestingly the annual volume of ablations and the number of hospitals performing ablations increased year over year but the rate of complications and length of stay also increased. A large number, almost more than a quarter of inpatient ablation procedures were actually performed in low volume hospitals and in turn were associated with an increased risk for complications with an odds ratio 1.26. Independent predictors of in-hospital complications and in-hospital mortality included complex ablations for atrial fibrillation and ventricular tachycardia, older age and a greater number of comorbidities. In addition to this, lower hospital volumes was an independent predictor of complications.                                 Thus the authors note that there has been a steady progressive in the number of in-hospital catheter ablation procedures. However, despite the increasing number, the number of periprocedural complications is increasing which may be partly mediated by taking in sicker patients from a complex procedures but also to performing these at lower volume centers. These findings are critical when considering the future of ablation strategies and ablation performance when we consider multicenter experiences or when we consider where certain procedures might be performed based on the experience of the operator or the institution. Why exactly it is that lower volume centers of higher complication rates still needs to be evaluated. However, it should be understood that ablations are  complex procedures and thus require a certain amount of experience in order to allow for procedural efficacy and safety similar to any cardiac surgery or other procedure. It remains to be understood what the number of procedures to be able to be felt to be competent and safe should be. But, these findings should be considered by all providers based on their own personal experience and based their own personal numbers.                                 Staying with the realm of catheter ablation, we will next review an article by Haldar et al., published regarding Catheter ablation vs electrophysiologically guided thoracoscopic surgical ablation in longstanding persistent atrial fibrillation: The CASA-AF Study in last month's edition of Heart Rhythm.                                 In this article, they sought to evaluate catheter ablation outcomes for longstanding persistent atrial fibrillation as compared with those of thoracoscopic surgical ablation. There's a limited amount of data comparing these two methodologies for ablation. They included 51 patients with de novo symptomatic atrial fibrillation. 26 underwent thoracoscopic surgical ablation and the remainder underwent stepwise left atrial ablation with a primary end point being single-procedure freedom from atrial fibrillation and atrial tachycardia lasting >30 seconds without antiarrhythmic drugs at 12 months. They noted that single- and multi procedure freedom from atrial fibrillation was higher in the surgical ablation group than in the catheter ablation group. Namely the overall success rate from the surgical ablation group was 73% versus 32% in the catheter ablation group. It should be noted that there was testing of the surgical ablation lesion set by electrophysiologists that was felt increased success rate in achieving acute conduction block by 19%. It also should be noted that the complication rate in the surgical ablation group, was significantly higher than the catheter ablation group, namely 27% versus 8%. This did not reach statistical significance however, possibly due to the low numbers considered.                                 The conclusion from the authors was that meticulous electrophysiologically guided thoracoscopic surgical ablation as a first line strategy in long standing persistent atrial fibrillation, may provide excellent single procedure success rates as compared with traditional catheter ablation. However again, there is an increased upfront risk of nonfatal complications. These considerations are important when thinking about what strategy to use in specific patients. Whether at a large level, thoracoscopic surgical ablation should be routinely used is still unclear and larger studies are likely needed to compare different modalities of ablation to better evaluate which is the right one for which patients.                                 Again staying in Heart Rhythm in 2017, we next review an article by Sheldon et al., published regarding Catheter ablation in patients with pleomorphic, idiopathic, premature ventricular complexes.                                 When a patient presents with idiopathic PVCs that are a single monomorphic focus, it is often considered reasonable to ablate them. However when patients have pleomorphic PVCs or polymorphic PVCs, the role of ablation is less clear and often considered more complex. Thus in this study, Sheldon et al., sought to evaluate patients who underwent ablation with pleomorphic PVCs. They reviewed about 100 consecutive patients 31% of whom had pleomorphic versus 69% who had monomorphic PVCs, however all of who were considered idiopathic. They noted the overall success rate was lower in patients with pleomorphic PVCs, namely 71% versus 90%. In fact, the presence of pleomorphic PVCs was independently associated with unsuccessful ablation. Also, pleomorphic PVCs more often had an epicardial origin than did monomorphic PVCs. And repeat ablation procedures were required in almost 20% of the cohort. Interestingly, three of the patients who came back for another procedure, had an increase of a nonpredominant PVC and one patient had a newly emerged PVC focus.                                 The conclusion by Sheldon et al. Was the presence of pleomorphic PVCs can affect ablation outcomes but it's still possible to achieve successful elimination of the predominant PVC even if not all PVCs are targeted. Furthermore, they suggested that most recurrences are due to reemergence of the originally targeted predominant PVC morphology though sometimes other PVC morphologies may arise. Larger scale evaluation is still necessary to understand when a patient should be taken to ablation and when not. We recognize that sometimes the presumption of idiopathic might be due to a lack of consideration of other ideologies such as subclinical inflammation that can be related to myocarditis or sarcoidosis or other finding. Thus it should always be considered what the actual underlying substrate is with rigorous imaging such as MRI or PET scanning. However, the findings by Sheldon et al. suggest that just because there are multiple PVC morphologies present, does not necessarily mean that they cannot be ablated.                                 Switching gears away from PVCs, we next review an article by Romero et al. published in Heart Rhythm this past month entitled Emergence of atrioventricular nodal reentry tachycardia after surgical or catheter ablation for atrial fibrillation: Are we creating the arrhythmia substrate?                                 They reviewed patients who had AVNRT ablation performed and sought to evaluate how many of them had prior surgical or catheter ablation for atrial fibrillation. They reviewed cases of ablation for specifically persistent atrial fibrillation who eventually required a repeat ablation procedure and had a diagnosis of AVNRT at that time. A total of nine patients were identified meeting these characteristics. All of these patients were noted to have evidence of atrial fibrosis in the septum or proximal CS, and in fact six had undergone ablation either at the septum or the coronary sinus ostium or body and the other three had inferior mitral lines at a surgical MAZE approach. All had typical AVNRT inducible that was abolished with slow pathway ablation, though five required ablation in the roof of the coronary sinus or on the mitral valve annulus.                                 Thus Romero et al. concluded that ablation involving the septum or proximal CS may create a substrate that can induce AVNRT. These findings are important when we consider ablation. Oftentimes when we do ablation, we think of a targeting substrate without thinking about the substrate we might create. Thus, rigorous evaluation for other mechanisms of tachycardia that one might not think of because of the absence of it during the index ablation should always be considered such as the creation of substrate for AVNRT. While most of us will consider atrial flutters or focal atrial tachycardias or macro reentry atrial tachycardias as the principle mechanisms of tachycardia in patients returning after prior atrial fibrillation ablation should also be considered that we might be creating substrate for other types of arrhythmias such as AVNRT.                                 The next article we will review is published in the American Journal of Physiology, Heart and Circulatory Physiology by Yang et al., entitled Effect of ovariectomy on intracellular calcium regulation in guinea pig cardiomyocytes.                                 It is believed that long-term deficiency of ovarian hormones after ovariectomy can alter cellular calcium handling mechanisms in the heart that can in turn result in the formation of a proarrhythmic substrates. This is important when considering possible arrhythmogenic mechanisms in women who might be undergoing ovariectomy or who might be in a post menopausal state. Thus in a series of animals, they evaluated the effective of ovariectomy as well as estrogen supplementation to ovariectomized animals on calcium handling at the level of the heart. They demonstrated that the ovariectomized guinea pig cardiac myocytes had higher frequencies of calcium waves and isoprenaline challenged cells displayed more early after depolarizations after ovariectomy. In addition to this, they noted the observations of calcium regulation alternations were not observed in myocytes from ovariectomized guinea pigs who were supplemented with 17β-Estradiol suggesting that in fact, these changes in the arrhythmogenic substrate were due to ovarian hormone deficiency resulting in dysregulation of cardiac calcium.                                 While this was all performed at the level of guinea pigs, it is an important consideration again, as a potential mechanisms of cardiac arrhythmogenesis in women who might be undergoing ovariectomy or who might be post menopausal. In some cases ovarian hormones might be beneficial in regulating the arrhythmogenic substrate.                                 The next article we review is published in Heart this past month by Stewart et al., entitled Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients.                                 Syncope is probably one of the most difficult things that we treat in electrophysiology. In particular, vasovagal syncope. People have looked at different pacing maneuvers and specialized pacemakers for treatments. However, there's improving body of knowledge regarding other mechanisms, specific physiologic mechanisms that might underlie vasovagal syncope. This group in question had previously demonstrated that impaired post synaptic adrenergic responsiveness in those who have vasovagal syncope may be reversed by blocking nitric oxide synthase. Thus, they sought to evaluate volunteers who either had vasovagal syncope or were otherwise healthy, what the effect of a nitric oxide synthase inhibitor would be.                                 They demonstrated that arterial vasoconstriction is impaired in young vasovagal syncope patients but inhibiting nitric oxide synthase could correct this problem. Namely, that this might provide a potential mechanism of avoiding the changes in blood pressure associated with orthostatic intolerance resulting in vasovagal syncope. Whether or not this proves to be an ambulatory therapy still remains to be seen but at least in the acute study state within which these patients were evaluated, it suggests to be a potential promising target.                                 The next paper we review is also published in Heart this past month by Lazzerini et al., entitled Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes.                                 There is increasing evidence of the role systemic inflammation can play in arrhythmogenesis and particularly in acquired long QT syndrome in patients with sarcoid or myocarditis and other disease states is well recognized that ventricular arrhythmias that are potentially life threatening can happen. What the role of correcting this inflammatory state is, is less clear. However, this group decided to evaluate whether systemic inflammation may represent a currently overlooked risk factor contributing to torsades de pointes in the general population. They looked at 40 consecutive patients who experienced torsades and enrolled them to evaluate circulating levels of different inflammatory biomarkers and compared them with patients with active rheumatoid arthritis, comorbidity or healthy controls. They demonstrated that in the torsades group, 80% of patients showed an elevated inflammatory markers and in fact a definite inflammatory disease was identifiable in 18 of the 40 patients with 12 having acute infections, five having immune mediated diseases and one described as other.                                 Thus they proposed that systemic inflammation via elevated IL-6 levels could represent a novel QT-prolonging risk factor that can contribute to torsades. In their group they showed that CRP reduction was associated with IL-6 level decrease and resulted in QTC shortening. It remains to be seen whether this increased inflammatory pathway might be due to the torsades event itself or the cause. However, it does bring up the interesting question of whether or not systemic inflammation may in fact be causing untoward effects on normal arrhythmic profiles resulting in a greater risk of ventricular arrhythmias.                                 The next article we review is published by Kottkamp et al., entitled Global multielectrode contact mapping plus ablation with a single catheter: Preclinical and preliminary experience in humans with atrial fibrillation in this past month's issue of the Journal of Cardiovascular Electrophysiology.                                 Within the realm of catheter ablation for atrial fibrillation, There's a constant search for new approaches to achieve either more durable or quicker or safer pulmonary vein isolation. It is well recognized that pulmonary vein isolation is the cornerstone of atrial fibrillation ablation. In this particular paper, they sought to evaluate the utility of a catheter, namely a basket catheter that could allow for both diagnostic mapping as well as targeted ablation. This novel catheter has a distal multielectrode array with 16 ribs with 122 gold-plated electrodes. With each electrode being able to ablate, pace and able to measure tissue contact, temperature, current, and intracardiac electrograms. They noted in three patients that complete pulmonary vein isolation was achieved in all 12 and in most veins, PVI was achieved with a single placement in front of that respective vein though in one case there was a single gap requiring reapplication.                                 This suggests a new technique for quote unquote, single shot pulmonary vein isolation. Furthermore, the fact that multiple electrodes could be used to map at the same time as performing ablation, suggest that there might be opportunities for mapping more than just the veins themselves. What the safety and utility of this approach would be over other quote unquote, single shot approaches, such as laser and cryo based balloon systems, is unclear. Furthermore, whether or not they actually reflect a paradigm that offer additional utility due to the ability for more mapping, also remains to be seen. However, the critical portion of understanding these different tools is being able to differentiate them in practice and understanding what their relative values and opportunities are will be critical as one makes selections of which technologies to use.                                 The next article we review is published in Europace this past month by Hellenthal et al., entitled Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.                                 While we recognize that coronary artery disease causes the majority of sudden cardiac deaths in the older population. When we have a young patient who experiences sudden cardiac death, we always have to be concerned about the role of a genetic component. This is not just important for the patient themselves but also for family members who might still be alive. In this study they sought to determine the portion of underlying genetic heart disease among unexplained putative sudden cardiac death cases from a large German forensic departments.                                 The number included were only 10 patients who had sudden unexplained death aged 19 to 40 years. DNA was analyzed for 174 candidate genes and also genetic testing was offered to affected families. Amongst 172 forensic cases again, 10 cases of sudden unexplained death were identified and a genetic disposition was found in eight of 10 cases, with pathogenic mutations in three and variants of uncertain significance in five. Furthermore, subsequent selective screening of the family members revealed two additional mutation carriers in family members who had not suffered from a sudden death event yet.                                 The role of molecular autopsy in patients is evolving. However, the amount of molecular autopsies that are sent are still too low. All patients who are young and die unexpectedly, might benefit from molecular autopsy beyond just traditional forensic pathology to understand whether or not there's a genetic predisposition that led to their event. This might help the family members of that affected individual, especially in understanding whether or not they may also be at risk.                                 The next article we review is by Constantino et al., entitled Neural networks as a tool to predict syncope risk in the Emergency Department in Europace this past month.                                 Many patients when they pass out immediately come into the emergency department. However, it can be very difficult to understand what the risk of that syncope patient is and thus many are automatically admitted to the hospital despite the fact that history might provide a lot of data. In this study, Constantino et al., sought to evaluate the utility for artificial neural networks in stratifying risk in patients presenting with syncope to the hospital. They analyzed individual level data from three prior prospective studies and included a a cumulative sample of 1,844 patients. They included ten variables from patient history, ECG, and the circumstances of syncope to train and test the neural network. They actually had two different approaches used for training and validating neural network given the exploratory nature of the study. They found that they could identify adverse events after syncope with a sensitivity if 95% if they used one approach versus 100% if they used an approach that considers more factors.                                 Thus the study suggested that artificial neural networks could effectively predict the short-term risk of patients with syncope after presenting to the emergency departments. They did not seek to address what the predictive capability of the artificial neural network would be when compared with traditional clinical judgment and existing rule sets that might exist in various emergency departments. The reason this study's important is that as artificial neural networks become more robust we might find that their role in complementing physician decision making might become more and more important. This is especially true on the front lines amongst emergency department physicians or in other groups and consideration of employment of novel technologies or rule sets or methodologies to augment decision making on risk of patients who are being evaluated might need to be considered. It also might help individual stratify patients into those that require sooner evaluation.                                 The final article we review is published in the Journal of Interventional Cardiac Electrophysiology this past month by Schmier et al., entitled Effect of battery longevity on costs and health outcomes associated with cardiac implantable electronic devices: a Markov model-based Monte Carlo simulation.                                 Economic effects of increasing utilization of cardiac implantable electronic devices is of increasing concern. We also note that a lot of focus goes on what the battery life of a device is. However, how that battery longevity might affect overall cost and health outcomes is less clear. Thus in this study, Schmier et al., sought to develop a Monte Carlo Markov model simulation model to evaluate what happens to patients based on the battery longevity. They sought evaluations such as infection and non-infectious complication rates as well as overall costs over the lifetime of that individual patient. These outcomes were largely derived from Medicare data. They noted that an increase in battery longevity was an associated reduction in the number of revisions needed by 23%, the number of battery changes needed by 44%, the number of infections by 23%, the number of non-infectious complications by 10% and total costs per patient by 9%.                                 Thus, they demonstrated that using batteries that have longer longevity could be associated with fewer adverse outcomes and reduced healthcare costs. The understanding of the magnitude of the cost benefits of extended battery life is critical and how to optimize the battery life is also critical. It might be that as we move forward, when encountering a situation or a patient in which the battery life is far less than expected, consideration of the reasons why that battery life was limited will be critical in order to optimize the ongoing chronic care of that patient. Both to reduce the burden on the healthcare system and to improve that individual patient's long term outcomes in terms of infectious risk or other issues.                                 This is primarily simulation model and was not necessarily tested in a prospective fashion though this would be quite difficult given the long duration over which would be required to see a lot of these beneficial costs and complication rate effects. However, it is provocative in the fact that it allows us to understand that there might be benefits from taking further care in selecting not just the right device based on indication but the right device based on patient age, the number of general changes one expects a patient to have and what the longevity of that patient is expected to be.                                 I appreciate everyone's attention in these key and hard hitting articles that we have just focused on from this past months of cardiac electrophysiology across the literature. Thanks for listening. Now back to Paul. Paul Wang:         Thanks Suraj. You did a terrific job surveying all journals for the latest articles on topics of interest in our field. There's not an easier way to stay in touch with the latest advances. These summaries and a list of all major articles in our field each month can be downloaded from the Circulation, Arrhythmia and Electrophysiology website. We hope you'll find the journal to be the go to place for everyone interested in the field. See you next month.    

Paul Wang:         Welcome to the monthly podcast On The Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journals in the field.                                 In our first article, Elyar Ghafoori and associates examined the ability of late gadolinium enhancement MRI done immediately after ablation to predict edema and chronically even size. In a canine model, the authors created ventricular radiofrequency ablation lesions. All animals underwent MRI immediately after ablation. After one, two, four and eight weeks, edema and microvascular obstruction MVO, in enhanced volumes were identified in MRI. Immediately after contrast administration, the microvascular obstruction region was 3.2 times larger than the chronic lesion volume size in acute MRI. The authors found that microvascular obstruction region on acute late gadolinium enhancement images acquired 26 minutes after contrast administration most accurately predicts chronic lesion volume.                                 In the next article, Elad Anter and associates characterized the atrial substrate in patients with paroxysmal atrial fibrillation and obstructive sleep apnea. The authors examined 86 patients with paroxysmal atrial fibrillation, 43 with moderate obstructive sleep apnea and 43 without obstructive sleep apnea. The right atrial and left atrial voltage distribution conduction velocities in electrogram characteristics were examined. The authors found that patients with obstructive sleep apnea had lower atrial voltage amplitude, slower conduction velocities, and higher prevalence of electrogram fractionation. Most commonly, the left atrial septum was an area of atrial abnormality while at baseline the pulmonary veins with the most frequent triggers for atrial fibrillation in both groups after pulmonary vein isolation in patients with obstructive sleep apnea had an increased incidence of extrapulmonary vein triggers, 41.8% versus 11.6%, p=0.003. The one year arrhythmia-free survival are similar between patients with and without obstructive sleep apnea, 83.7% and 81.4%, respectively.                                 In comparison, control patients with paroxysmal atrial fibrillation and obstructive sleep apnea who underwent pulmonary vein isolation alone without ablation of extrapulmonary vein triggers had an increased risk of arrhythmia recurrence, 83.7% versus 64.0%, p=0.03, suggesting that ablation of these triggers resulted in improved arrhythmia-free survival. A randomized trial would be needed to prove this relationship.                                 In the next article, Iolanda Feola and associates demonstrated that optogenetics may be used to induce and locally target a rotor in atrial monolayers. The authors used neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel, calcium-translocating channelrhodopsin. These monolayers were subjected to patterned illumination to induce the single, stable, and centralized rotor by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching an unexcitable boundary, did not lead to termination. Instead, electrical waves started to propagate along the circumference of block. If, however, core-spanning lines of block reached at least one unexcitable boundary, reentrant activity was consistently terminated by wave collision, suggesting that this may be a key mechanism for rotor elimination.                                 In our next study, Adam Barnett and associates used data from the outcomes registry for better informed treatment of atrial fibrillation ORBIT-AF to determine how frequently patients receive care that was concordant with 11 recommendations of the 2014 AHA, ACC, HRS A-fib guidelines pertaining to antithrombotic therapy rate control in anti-arrhythmic medications. The authors also analyzed the association between guideline concordant care and clinical outcomes at both the patient's level and center level. The authors study 9,570 patients with the median A 275, median CHA2DS2-VASc score of 4. A total of 62.5% or 5,5977 patients received care that was concordant with all guideline recommendations for which they were eligible. Rates of guideline concordant care was higher in patients treated with providers, with greater specialization in arrhythmias; 60.0%, 62.4%, 67.0% for primary care physicians, cardiologists and electrophysiologist, respectively; p less than 0.001. During a median of 30 months of follow up, patients treated with guideline concordant care had a higher risk of bleeding hospitalization; hazard ratio, 1.21. Similar risk of death, stroke, major bleeding can all cause hospitalization.                                 In our next article, Hui-Chen Han and associates conducted electronic search of PubMed and Embase for English scientific literature articles to characterize the clinical presentation, procedural characteristics, diagnostic investigations and treatment outcomes of all reported cases of atrioesophageal fistula. Out of 588 references, 120 cases of atrioesophageal fistula were identified. Clinical presentation occurred between 0 and 60 days postablation with a median of 21 days. The most common presentations were fever 73%, neurological 72%, gastrointestinal 41%, and cardiac 40% symptoms. Computed tomography of the chest was the commonest mode of diagnosis, 68% although six cases required repeat testing. Overall mortality was 55%. In conclusion, the authors reported that atrioesophageal fistula complicating atrial fibrillation is associated with a very high mortality 55% with significantly reduced mortality in patients undergoing surgical repair 33% compared to endoscopic treatment 65%, and conservative management 97%. Odds ratio adjusted 24.9; p less than 0.01 compared to surgery. Neurological symptoms adjusted odd ratio 16.0. In GI bleed, adjusted odds ratio 4.2, were the best predictors of mortality.                                 In the next article, Wei Ma and associates reported that the site origin of left posterior fascicular ventricular tachycardia may be predicted using 12-lead EC morphology in the HIS-ventricular or H-V interval. The authors studied 41 patients who underwent successful catheter ablation of left posterior fascicular ventricular tachycardia. The location of the site of origin was separated into proximal, middle, and distal groups with H-V being greater than zero milliseconds in the proximal group, H-V zero to minus 15 milliseconds in the middle group, and H-V less than negative 15 milliseconds in the distal group. The earliest presystolic potential ratio that is PP-QRS interval during VT divided by the H-V interval during sinus rhythm was statistically significantly different between the three groups, 0.59, 0.45 and 0.31, respectively. In addition, the QRS ratio in the proximal group 114 milliseconds was significant nearer compared to the middle group 128 milliseconds and the distal group 140 milliseconds. The QRS duration in the ratio R to S in leads V6 and lead-1 could predict a proximal or distal origin of left posterior fascicular ventricular tachycardia with high sensitivity and specificity.                                 In our next article, Niv Ad and associates examined the safety and success of on-pump minimally invasive stand-alone Cox-Maze 3/4 procedure via right mini-thoracotomy in 133 patients with nonparoxysmal atrial fibrillation five years after surgery. The mean follow-up was 65 months in a patient population with a mean age of 57.3 years, mean left atrial size of 4.9 centimeters, mean AF duration of 51 months and 78% with longstanding persistent atrial fibrillation. All procedures were performed with no conversion to mid-sternotomy. No renal failure, strokes or operative mortality in less than 30 days. They reported a TIA in one patient, re-operation for bleeding in two patients, and median length of stay in four days. At five years, 73% of patients were in sinus rhythm off anti-arrhythmic drugs following a single intervention.                                 In the next article, Richard Soto-Becerra and associates reported that unipolar endocardial electro-anatomic mapping may be used to identify scar epicardially in chagasic cardiomyopathy. In 19 sick patients, a total of 8,494 epicardial and 6,331 endocardial voltage signals in 314 epicardial and endocardial match pairs of points were analyzed. Basolateral left ventricular scar involvement was observed in 18 out of 19 patients. Bipolar epicardial and endocardial voltages within scar were low, 0.4 and 0.54 millivolts, respectively in confluent indicating a dense transmural scarring process. The endocardial unipolar voltage value with the newly proposed less than of equal to four-millivolt cutoff predicted the presence and extent of epicardial bipolar scar, p less than 0.001.                                 In our next article, Bing Yang and associates reported the results of the stable SR study, which is a multicenter clinical trial of 229 symptomatic nonparoxysmal atrial fibrillation patients random-eyed one-to-one to two ablation strategies. In the stable SR group following pulmonary vein isolation, cavotricuspid isthmus ablation in conversion to sinus rhythm left atrial high density mapping was performed. Areas of low voltage and complex electrogram were further homogenized and eliminated, respectively. Dechanneling was done if necessary. In the step-wise group, additional linear lesions and defragmentation were performed. The primary endpoint was freedom of documented atrial tachyarrhythmias lasting 30 seconds or more after a single ablation procedure without anti-arrhythmic medications at 18 months. At 18 months, success according to intention-to-treat analysis was similar in the two arms with 74.0 success in the stable SR group and 71.5% success in the step-wise group; p=0.3. However, shorter procedure time reduced fluoroscopic time after pulmonary vein isolation and shorter energy delivery time were observed in the stable SR group compared to the step-wise group.                                 In the final paper, Alan Sugrue and associates studied the performance of a morphological T-wave analysis program in defining breakthrough long QT syndrome arrhythmic risk beyond the QTc value. The author studied 246 genetically confirmed LQT1 patients and 161 LQT2 patients with a mean follow-up of 6.4 years. A total of 23 patients experienced more than one breakthrough cardiac arrhythmic event with 5 and 10-year event rates of 4% and 7%. Two independent predictors of future long Qt syndrome-associated cardiac events were identified from the surface ECG using a proprietary novel T-wave analysis program. The authors found that the most predictive features included the left slope of T-wave in V6, hazard ratio of 0.40, and T-wave center of gravity X-axis in lead-1, hazard ratio 1.9, C statistic of 0.77. When added to QTc, discrimination improved from 0.68 for QTc alone to 0.78. Genotype analysis showed weaker association between these T-wave variables in LQT1 triggered events while these features were stronger in patients with LQT2 and significantly outperformed the QTc interval.                                 That's it for this month, but keep listening. Suraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcast On the Beat. Take it away, Suraj. Suraj Kapa:          Thank you, Paul. This month, we will again focus on hard-hitting articles from across the electrophysiological literature. I am Suraj Kapa and we're particularly focusing on articles published in October 2017.                                 The first article we will focus on is within the realm of atrial fibrillation specifically related to anticoagulation. In Journal of the American Heart Association in Volume 6, Issue 10, Lin, et al. sought to develop a prediction model for time in therapeutic range in older adults taking vitamin K antagonists. As we know, time in therapeutic range is critical for management of patients on vitamin K antagonists. As poor time in therapeutic range either due to subtherapeutic or supratherapeutic INRs, can lead to increased bleeding or thromboembolic risk. While novel oral anticoagulants have improved care of patients requiring anticoagulation, many patients either due to cost or due to other factors are unable to take the novel oral anticoagulants and thus must be maintained on vitamin K antagonists. In this study, Lin, et al. Used well-over 2,500 patients to create training and validation sets and thereby create two models for estimating time in therapeutic range. Through this, they created a simple model term PROSPER consisting of seven variables including pneumonia, renal dysfunction, prior bleeding, hospital stay more than seven days, pain medication use, lack of access to structured anticoagulation services, and treatment with antibiotics.                                 Using this, they showed that they can predict time in therapeutic range greater than 70% as well as thromboembolic and bleeding outcomes better than other existing time in therapeutic range scoring systems, such as the same TT2R2 score. The reason these scores are important are both to help patients understand when they may be at risk for not maintaining a time in therapeutic range and to assist them in identification of the right anticoagulant methodology or strategy. Also, perhaps to prospectively consider if we can identify patients who may require more intensive monitoring or structured therapy strategies. However, one must also consider that for scores like this, utilization is always critical. In other words, continuous validation of the scoring system must be done in order to make sure it's applicable across populations and across different groups of people in different communities.                                 Next, within the realm of anticoagulation and atrial fibrillation, we'll review the article by Chang, et al. published in JAMA in Volume 318, Issue 13 entitled Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding Non-Valvular Atrial Fibrillation. With any new drug that comes out, there's always the possibility of various medication interactions. The source of these medication interactions might be variable. They might include direct effects of other medications on systems by which the primary drug is metabolized. Also, might be due to synergistic effects of medications that might be unpredictable or effects on different aspects of systems the drugs are trying to treat. Thus oftentimes, larger population studies are required before one can appreciate drug interactions that might exist. This is particularly true with novel oral anticoagulant drugs. Part of the promise of the novel oral anticoagulants was that because of the extensive medication interactions associating vitamin K antagonists, the availability of the drug perhaps with fewer medication interactions resulting in alteration and bleeding or thromboembolic tendency will be very important.                                 In this important paper, Chang, et al. reviewed the effect of other medications on major bleeding events in patients on non-vitamin K oral anticoagulants such as dabigatran, apixaban, and rivaroxaban. Amongst over 91,000 patients, they noted that the concurrent use of amiodarone, fluconazole,  rifampin, and phenytoin compared with the novel oral anticoagulant alone was associated with a significant increase many times by odds ratio of 100 in risk of major bleeding. Several drugs including atorvastatin, digoxin, erythromycin or clarithromycin when used concurrently with NOACs interestingly were associated with the reduced risk of bleeding without elevating thromboembolic risk. The recent advent of NOACs in clinical use especially in patients who might be taking other medications always need to be considered in the context of how the other medications might affect the bleeding or thromboembolic risk. One of the key findings in this publication is the potential interaction with amiodarone and how concurrent use of amiodarone may increase the risk of major bleeding. Because of the general lack of tools to monitor the effects of NOACs on bleeding risk in patients, one needs to consider these population studies and whether or not there might be synergistic effects between medications going forward.                                 Unfortunately, we cannot adopt guidelines purely based on this data as to whether or not a dose adjustment should occur or whether or not the medication can be used at all. However, it does highlight the care that should be taken when using many of these drugs in conjunction with NOACs.                                 Finally within the realm of anticoagulation and atrial fibrillation, we'll review the article by Cannon, et al. in The New England Journal of Medicine entitled Dual Antithrombotic Therapy with the Dabigatran After PCI in Atrial Fibrillation. In this study, Cannon, et al. sought to systematically review the role of a warfarin strategy post-PCI versus dabigatran strategy post-PCI. They randomized patients to use of a combination of warfarin, aspirin, and a P2Y12 inhibitors such as clopidogrel post-PCI versus using dabigatran plus a P2Y12 inhibitor. They demonstrated that dual therapy approach with dabigatran resulted in significantly lower bleeding events than the triple antithrombotic/antiplatelet therapy group. There was no difference in adverse events including thromboembolism, unplanned revascularization or death between the groups. These findings were irrespective of whether patients were on 110 mg of dabigatran or 150 mg of dabigatran. These findings suggest that a dual therapy approach in the post-PCI setting with the NOACs as the dabigatran and the P2Y12 inhibitors such as clopidogrel lowers bleeding risk without increasing risk of major adverse events including thromboembolism or stent thrombosis after PCI.                                 However, it should be noted that one major criticisms of this trial is that the incremental bleeding risk conferred by aspirin could not be accounted for in the triple therapy cohort as aspirin was not used in the dual therapy cohorts. Thus, one cannot necessarily say whether the same finding would have been noted in a warfarin plus P2Y12 inhibitor versus dabigatran plus P2Y12 inhibitor especially given recent evidence suggesting no incremental benefit of aspirin particularly for thromboembolic risk associated with atrial fibrillation. However, the critical element of these findings is that a strategy excluding aspirin where dabigatran plus the P2Y12 inhibitor are used post-PCI might be actually safe.                                 Changing gears, we will next focus on an article within the realm of cardiac mapping and ablation in atrial fibrillation. This was published in the Journal of the American College of Cardiology in Volume 70, Issue 16 by Prabhu, et al. entitled Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. In this study, Prabhu, et al. studied in the multicenter randomized clinical trial the effect of catheter ablation for atrial fibrillation in the setting of left ventricular systolic dysfunction versus medical rate control. They looked at the change in ejection fraction over a follow-up of six months. A total of 68 patients were randomized in the study. They demonstrated an absolute improvement in EF by 18% in the ablation group versus 4% in the rate control group, with also a greater rate of EF normalization with ablation. In fact, over 50% of patients had EF normalization after ablation whereas only about 9% had a good medical rate control.                                 Furthermore, the improvements in EF correlated with the absence of late gadolinium enhancement on MRI and in the medical rate control group an average heart rate less than 90 beats per minute was achieved across the population randomized this approach. These findings are somewhat contrary to other studies that suggested that a rate versus a rhythm control approach were not really much different in patients with reduced left ventricular systolic function. These challenges are paradigm by suggesting that in fact successful restoration of normal rhythm in patients postablation can actually confer improvement in ejection fraction in some patients even when rate controlled. The success rates that should be noted in this study were similar to those published in most existing literature with about 56% of patients without further atrial fibrillation after a single ablation off medications and a success rate of 75% after a single ablation on medications. While the number of patients included are small and thus may be difficult to challenge the paradigm that was created, the rate versus rhythm control are equivalent in patients with reduced systolic function.                                 This finding should raise awareness that it is quite possible that there might actually be benefits in restoring normal rhythm by modern approaches in patients with reduced systolic function.                                 Moving on, still within the realm of atrial fibrillation, however, we'll next review the article by Aronsson, et al. in Europace Volume 19, Issue 10 entitled Designing an Optimal Screening Program for Unknown Atrial Fibrillation: A Cost-Effectiveness Analysis. More and more with an understanding that atrial fibrillation is essentially of epidemic proportions, but many patients tend to be asymptomatic and yet having an elevated stroke risk. People are focusing on how do we screen these populations in a manner that is both cost-effective as well as strategic. Aronsson, et al. tried to use computer simulation modeling to determine what the optimal age was to initiate screening for atrial fibrillation. They ran more than two billion different design screening programs that could be implemented at different age ranges and using data from published scientific literature. They tested these various screening programs. They demonstrated that the screening starting at the age of 75 was associated with the relatively low cost per gained quality adjusted life year. The overall cost at this level was 4,800 euros across the population for quality adjusted life year gained across that population.                                 The relevance of this publication while simulation model lies in highlighting the importance of considering what programs can we actually achieve in the modern day to better identify patients with atrial fibrillation who are not yet identified. Across the literature and in recent clinical meetings, there's a number of articles that are being published regarding the role of different strategies in identifying the asymptomatic, not yet diagnosed atrial fibrillation patients. This study presents an initial foray into systematizing programs that might be applied to recognition of these patients.                                 Along a similar course, we'll also review an article by Reiffel, et al. in JAMA Cardiology Volume 2, Issue 10 entitled Incidence of Previously Undiagnosed Atrial Fibrillation using Insertable Cardiac Monitors in a High-Risk Population: The REVEAL AF Study. In this study, Reiffel, et al. Reviewed the incidence of atrial fibrillation identified using implantable loop recorders in those with a high risk of stroke nearly a CHADS2 score of 3 or greater, but had not been previously diagnosed. It should be noted that while these patients have never been diagnosed with atrial fibrillation, 90% had nonspecific symptoms such as fatigue, dyspnea or palpitations, then theory could be attributed to atrial fibrillation. A total of 385 patients received monitors. They noted that by 30 months of monitoring, about 40% of patients have been identified as having atrial fibrillation that had not been diagnosed. If patients were only monitored for the first 30 days, however, the incident rate of atrial fibrillation in terms of new diagnosis was only 6%. In fact, the median time from device insertion to first episode of atrial fibrillation was almost four months at about 123 days.                                 In line with the previous discussed study by Arosson, et al., this study notes the importance of consideration of how we monitor patients at risk for stroke. The issue at hand is when we do screening, what is enough. The strategies used to identify atrial fibrillation of patients raised from advising on twice daily poll checks, which when done by the patient regularly might allow for identification of atrial fibrillation if they do it well to doing a single ECG, to doing a 24-hour Holter, to doing a 30-day monitor, to doing things like implantable loop recorders. However, this study by Reiffel, et al. suggests the a 30-day continuous monitor is truly insufficient if there is a high concern for atrial fibrillation. Thus with the goals to identify atrial fibrillation on high-risk patients or whether a significant clinical suspicion, one should always consider longer term monitoring by this study.                                 Finally, within the realm of atrial fibrillation, we'll review the article by Tilz, et al. published in Europace Volume 19, Issue 10 on left atrial appendage occluder implantation in Europe, indications anticoagulation post-implantation, results of the European Heart Rhythm Association survey. Currently, there's a high level of utilization of left atrial appendage occlusion for patients with atrial fibrillation who cannot otherwise be on a novel oral anticoagulants in Europe. Tilz, et al. performed a survey of providers performing these procedures. They found that about 52% of those centers performing left atrial appendage occlusion had electrophysiologist performing it as opposed to the remainder using interventional cardiologists. The most common indication for implantation was in those with high risk for stroke and with absolute contraindication to oral anticoagulation or history of bleeding. However, was most interesting from their study was that there was a very wide ranging practice in management after implantation in terms of use of antiplatelets for anticoagulants with 41% prescribing no therapy after implantation. There is even greater variability in therapies for patients who are found to have a thrombus after left atrial appendage occlusion ranging from no therapy to surgery.                                 These findings highlight the difficulty in managing practice patterns with novel technologist and in particular with left atrial appendage occlusion. The highly heterogeneous practice pattern found here suggests that large-scale population outcomes will be difficult to understand unless we understand the individual practice variation that is occurring such as considering what medications patients were prescribed on in the post-implant period or how patients were included in terms of whether or not they met the standard criteria. Furthermore, when a complication occurs such a thrombus septal left atrial appendage occlusion one might suspect that the implications of different strategies such as not doing any therapy all the way to routinely doing surgery tumor to clot should be considered.                                 Next, we will move on to the realm of ICDs, pacemakers, and CRT. First, reviewing the article by Pokorney, et al. published in Circulation in Volume 136, Issue 15 entitled Outcomes Associated With Extraction Versus Capping and Abandoning Pacing and Defibrillator Leads. In this study, Pokorney, et al. reviewed these two different approaches in abandoned leads amongst 6,859 patients. They found that extraction was associated with the lower risk of device infection, but there was no association between difference in mortality, need for future lead revision, or need for future extraction. This involved patients in the Medicare age group, but extraction patients of note, tended to be younger with fewer comorbidities, more often female and had a shorter lead dwell time. While they're statistically different, however, the actual number of years by which patients tended to be younger or to have a shorter lead dwell time was only a year.                                 The fact is that it is always hard to know what to do with an abandoned lead. Having more leads in the vascular system might lead to venous stenosis or might lead to patients having future problems when they need an extraction because of infection, or might make it harder to manipulate this in the vascular space. Thus whether extracting abandoned leads as opposed to just capping them and leaving there needs to be considered when taking any patient in for a lead revision or a lead addition for other reasons. These findings suggest that extraction confer similar mortality risk but lower long-term infection risk than capping them. However, it should be noted this is retrospective data set and given the extraction patients already were younger and had their leads for relatively shorter durations with your comorbidities, they might have reflected to healthier population anyway. However, these data are suggestive and highly the need for further study into whether a more aggressive approach with abandoned lead should be considered. Without randomized data, it will not be for certain.                                 Next, also within the realm of lead extraction, we'll review the article by Bongiorni, et al. published in the European Heart Journal in Volume 38, Issue 40 entitled The European Lead Extraction Controlled Study: A European Heart Rhythm Association Registry of Transvenous Lead Extraction Outcomes. This prospect of registry on lead extraction the largest to dates, Bongiorni, et al. reviewed safety and complications in addition to relationship to the type of center. They noted that the overall hospital major complication rate was 1.7% with mortality rate of 0.5% associated with lead extraction. The most common complication was actually pericardial synthesis, need for a chest tube or need for surgical repair. Overall, success rates for lead extraction in terms of complete removal of all lead components was 97%. However, it should be noted the overall complication rate and success rates were better in high-volume centers than low-volume centers. These findings are consistent with prior data published by [Desmott 35:22] and others, suggesting that more experience associates with better outcomes in lead extraction. However, these data represent the largest prospective registry on lead extraction and confirm the safety and efficacy of overall current practices.                                 These better data on modern lead extraction may help facilitate discussions with patients regarding actual outcomes and also decisions on whether or not extraction should be engaged in individual practices.                                 Next, we'll review the article by Aro, et al. in the realm of sudden death cardiac arrest entitled Electrical Risk Score Beyond Left Ventricular Ejection Fraction: Prediction of Sudden Cardiac Death in the Oregon Sudden Unexpected Death Study in the Atherosclerosis Risk and Communities Study, published in the European Heart Journal in Volume 38, Issue 40. In this study, Aro, et al. reviewed what features beyond ejection fraction could predict sudden death in community cohorts. They specifically focus on the electrocardiogram and demonstrated an electrocardiogram risk score based on the presence or absence of a number of features related to heart rate, left ventricular hypertrophy, QRS transition zone, QTc, and others. They found that amongst those patients with a left ventricular ejection fraction greater than 35%, the presence of four more of these ECG abnormalities confer an odd ratio of sudden death of 26.1. The importance of this article is highlighting how more complex considerations of clinical risk might help in further adjudication of sudden death in poorly characterized cohorts.                                 While most studies have concluded that addition of a variety of additional features such a T-wave alternans do not really confer incremental benefit beyond the ejection fraction in adjudicating sudden death risk and in helping decision making regarding ICD implantation. The fact is that more complex analyses that might exist in more nonlinear approaches or consider more advanced features, the ECG and combination, might confer some benefit in poorly characterized populations such as those with moderately reduced ejection fraction between 35 and 50. We know that while those with an ejection fraction less than 35% is a population have a higher risk within that population, the majority of patients who suddenly die do not have an EF less than 35%. Thus, identifying patients without an EF less than 35% who might be at risk is important. This study by Aro, et al. indicates one potential option to help discriminate patients who might not fit within normal categories for sudden death adjudication and did not fit neatly within the trials. However, prospect of evaluation of application of scoring systems either this one or others that may come in the future will be critical.                                 Changing realms yet again, we'll focus on cellular electrophysiology on an article by Kofron, et al. entitled Gq-Activated Fibroblasts Induce Cardiomyocyte Action Potential Prolongation and Automaticity in a Three-Dimensional Microtissue Environment, published in The American Journal of Physiology, Heart and Circulatory Physiology in Volume 313, Issue 4. In this publication, Kofron, et al. demonstrated that in this three-dimensional microtissue model, fibroblasts cause effects on the normal action potential in the surrounding environment leading to proarrhythmogenic automaticity. This model effectively demonstrated the activation of this fibroblast alone taken out of context by other triggers such as abnormalities of innervation, et cetera, could probably contribute to arrhythmogenicity into these hearts. It is well recognized in other studies that fibroblasts don't just cause proarrhythmic effects because of myocardial disarray. In fact, they can have paracrine effects on surrounding cells. This study by Kofron, et al. further highlights those potential effects. The presence of fibroblast amidst cardiomyocytes do not cause proarrhythmic tendency purely by shift in myocardial conduction direction, but also results from the effects of fibroblast once activated on these running cardiomyocytes action potentials of cells.                                 This study is suggesting specifically proarrhythmogenic arrhythmogenicity related to automaticity in those cardiomyocytes that are adjacent to fibroblast, highlights potential future targets for therapies and also highlights potential mechanisms by which arrhythmias might occurrence population.                                 Changing gears, we next look at genetic channelopathies in one article within the realm of Brugada syndrome and the second article within the realm of predicting QT interval. First, Hernandez-Ojeda, et al. published an article in The Journal of the American College of Cardiology Volume 70, Issue 16 entitled Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up. Amongst the 104 patients with long-term follow-up nearly greater than nine years on average, they noted a rate of appropriate therapy was very common especially in secondary prevention patients, however, was as much as 9% in otherwise asymptomatic patients. Appropriate ICD therapies, however, especially amongst asymptomatic patients were exclusively in those spontaneous type I Brugada ECG patterns and inducible ventricular arrhythmias, or those obviously the secondary prevention devices who have prior spontaneous ventricular arrhythmias. However, what is more interesting is that more than 20% of patients had some ICD-related complication. Furthermore, the overall incidence of inappropriate shocks was 8.7%, nearly the same rate as appropriate ICD therapies in the primary prevention population. These findings highlight that there is in fact a reasonable incidence of ventricular arrhythmic events needing ICD therapy even in asymptomatic Brugada patients.                                 However, I think the most striking finding is the high incidence of device-related complications of a follow-up, which highlights the need for considered selection and adequate device programming to avoid inappropriate ICD shocks and finally the need for regular follow-up of these relatively young patients receiving ICDs who might be more prone to complication with the long-term.                                 Changing gears, we'll next review an article by Rosenberg, et al. published in Circulation Genetics in Volume 10, Issue 5 entitled Validation of Polygenic Scores for QT Interval in Clinical Populations. Using more extensive genomic analyses, Rosenberg, et al. used populations and real-world cohorts including 2,915 individuals of European ancestry and 366 individuals of African ancestry. They demonstrated that clinical variables could account for about 9 to 10% of variation in QTc in Europeans and 12 to 18% in African ancestry individuals. However, interestingly, polygenic scores provided incremental explanation of a QTc variation but only in individuals of European ancestry. The reason we find this article interesting is the importance of understanding how much genetics can actually tell us and how what it can tell us might vary between difference, individuals of different backgrounds thus how we apply findings from one study to any other study. In the area of genetic testing, the Holy Grail is fully identifying overall risk scores to tell the patient what they may have without having to rely on clinical studies or other clinical variables. However, we do know that there is both an environmental component as well as the genetic components.                                 This study by Rosenberg highlights the importance of potentially considering both. The issue with the article, however, is the fact that while there was clear benefit of the polygenic score in patients of European ancestry, the African ancestry patients reflect the much smaller population almost one-eighth that of the patients included of European ancestry. Also, European versus African ancestry tend to be very broad-based terms. Whether or not there is greater polygenic variation within those of African ancestry as compared to those Europeans ancestry is relatively unclear. Thus while this study should be taken with grain of salt, it should also be considered in the context of providing a foray into seeing how polygenic scores could augment or understanding of how question intervals might vary in a population of people and might be identified immigrant patients.                                 Moving to the realm of ventricular arrhythmias, we'll first review the article by Siontis, et al. published in Heart Rhythm Volume 14, Issue 10 entitled Association of Preprocedural Cardiac Magnetic Resonance Imaging with Outcomes of Ventricular Tachycardia Ablation in Patients with Idiopathic Dilated Cardiomyopathy. In this study, Siontis, et al. tried to identify whether or not use of preprocedural MRI had any impact on overall procedural outcomes. They compared in a more modern practice where they are routinely obtaining cardiac MRI versus prior practice where they do not routinely obtain preprocedural MRI for ablation in patients with idiopathic dilated cardiomyopathy. They demonstrated that moderate use of preprocedural MRIs was associated with significantly greater procedural success mainly 63% in the modern approach versus 24% previously. The importance of the study why is in trying to understand what the actual value of preprocedural cardiac MRI is when patients are undergoing VT ablation particularly with non-ischemic cardiomyopathy. VT ablation outcomes are notoriously even harder to predict in non-ischemic cardiomyopathy cohorts than ischemic cardiomyopathy cohorts. Improved procedural experience, however, or different technologies may also alter long-term outcomes.                                 Thus, because the populations were not randomized and rather retrospective with a discrete change in practice that occurred temporally and just did not vary in terms of utilization over the course of periods of time when success rates might not have been affected just by incremental procedural success is difficult. However, these data suggest that future studies into the incremental role of MRI for VT ablation are needed to determine its utility.                                 Next, we'll review an article by Ho, et al. published in The Journal of Cardiovascular Electrophysiology in Volume 28, Issue 10 entitled ECG Variation During Ventricular Fibrillation Than Focal Sources Due to Wavebreak, Secondary Rotors, and Meander. Ho, et al. in this publication reviewed the role of rotors and focal sources in ventricular fibrillation. They attempted VF induction of 31 patients and use the combination of surface ECG and biventricular basket catheters to create face mask. They showed there's three differences between those with ventricular fibrillation that was mediate by rotors and those with ventricular fibrillation mediated by focal sources. Specifically those with rotor-based VF had greater voltage variation, which they demonstrated zero wavebreak, secondary rotor formation and rotor meander. One of the most critical findings of this study is the fact that a one-size-fits-all approach to consideration of the mechanism of fibrillation is likely unreasonable in most patients. They discriminate between rotor-based ventricular fibrillation and focal source-based ventricular fibrillation and highlighted there are discrete features that differentiate the two populations.                                 While this should be considered an initial foray into understanding these patients, clinical and computational size will be important into understand how we can discriminate mechanisms of complex arrhythmias between patients to help understand, which patients might most benefit from a specific ablation approach or therapeutic decision. This might also apply to atrial fibrillation where multiple mechanisms may coexist in the same patient for the pathogenesis of the arrhythmia.                                 Finally, we'll review an animal model by Patterson, et al. published in The Journal of Cardiovascular Electrophysiology in Volume 28, Issue 10 entitled Slow Conduction Through an Arc of Block: A Basis for Arrhythmia Formation Postmyocardial Infarction. In this study performed in the University of Oklahoma, Patterson, et al. reviewed a novel basis for arrhythmia formation after MI in an animal model. Amongst 108 anesthetized dogs, they demonstrated the delay potentials may decrement over shorter pacing cycle lengths leading to potential premature ventricular beat initiation after sufficient delay of the second potential. Thus, they demonstrated that there is a Wenckebach-like patterns of delayed activation specifically within this arc of conduction block associated with the region infarcted. These findings suggest that even across line of apparent conduction block there may be a potential for premature beat formation due to very slow conduction and thus a novel mechanism of PVC formation following myocardial infarction. Furthermore, it might highlight the mechanism by which to induce PVCs in this patient population                                 Just because there is conduction block the region of baseline mapping further provocative maneuvers to initiate or to discriminate where there might be very slow conduction might be critical to elicit arrhythmia in some patients.                                 Next, within the realm of syncope. We focus on article by Baron-Esquivias, et al. published in The Journal of American College of Cardiology Volume 70, Issue 14 entitled Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The SPAIN Study. In this randomized double blind control study, Baron-Esquivias, et al. study the value of closed loop stimulation in the specific cohort of patients with cardio-inhibitory vasovagal syncope above 40 years of age. They demonstrated amongst 46 patients the closed loops stimulation was associated with the more than 50% reduction in syncopal spells in nearly three quarters of patients. However, it should be noted that up to 9% of patients continue to have syncope in your consistent frequency to prior. However, it should also be noted that sham cohort 46% of patients continue to have syncope while only a quarter were relieved. Syncope is one of the most challenging diagnosis to manage in electrophysiologic practice. This is both due to the heterogeneity of manifestation of syncope in terms of cause as well as the lack of many therapies that affect some of the autonomic features that mediate syncope. Largely, vasovagal syncope can be strategized into cardio-inhibitory and vasodilatory groups.                                 Generally, pacing will be more effective in theory for those more of a cardio-inhibitory than a vasodilatory component thus certainly patients can have both and thus that might be only partial attenuation of syncopal events by fixing the cardio-inhibitory by pacing but not the vasodilatory, which often requires medications. In this study, the use of closed loops stimulation seems to offer significant benefit in the specific population with cardio-inhibitory vasovagal syncope in age greater than 40 years. However, care should be taken not to necessarily apply these findings to patients not within this age group or within this diagnosis group.                                 Next within the realm of electrocardiography, we'll review an article by Yasin, et al. published in The Journal of Electrocardiology Volume 50, Issue 5 entitled Noninvasive Blood Potassium Measurement Using Signal-Processed, Single-Lead ECG Acquired from a Handheld Smartphone. Yasin, et al. reviewed the ability to determine changes in potassium level using the ECG. They demonstrated amongst 22 patients undergoing hemodialysis in whom estimation models could then be trained. The mean absolute error of ambulatory follow-up between the potassium estimated off of a single lead handheld smartphone-enabled ECG in the actual blood potassium was 0.38 milliequivalents per liter or a difference of 9% of the average potassium level. These findings suggest that in terms of clinical robustness a single lead smartphone-enabled handheld base ECG might be sufficient to estimate ambulatory potassium levels in patients who might be at high risk especially of hyperkalemia. The fact is that electrolytes and other abnormalities of a body homeostasis may be reflected in the ECG. However, whether the ECG may in turn be used to finally determine changes in characteristics such as electrolytes levels has not been very well described.                                 Previous work by the same group has suggested that the 12-lead ECG may be utilized to determine find potassium changes in patients undergoing hemodialysis. These findings while in small number of patients in this particular article highlights that ambulatory technologies such as the one they used here might in fact be utilized to discriminate potassium levels in patients who might be at risk of variations of potassium levels that can sometimes be life-threatening. Further validation will be required in larger populations, but this initial foray might create a paradigm for use of the ECG in ways beyond just looking for arrhythmias.                                 The final article we'll review is by Calzolari, et al. published in The Journal of American College of Cardiology, Clinical Electrophysiology in Volume 3, Issue 10 entitled In Vitro Validation of the Lesion Size Index to Predict Lesion Width and Depth After Irrigated Radiofrequency Ablation in a Porcine Model. In this paper published in the special of JACCEP focused on biophysics of ablation, Calzolari, et al. reviewed in vitro validation of lesion size indexing using radiofrequency ablation. Specifically, they reviewed the novel measure that incorporates not just contact force, power and time, but also impedance into predicting lesion quality. They noted that while lesion with in depth did not correlate with power or contact force alone, it did with either the lesion size indexing tool that they created and also with the force-time integral. However, the lesion size indexing where impedance was included was incrementally better than force-time integral. The truth is that improved prediction model lesion size inadequacy are critical during radiofrequency ablation.                                 Predicting lesion formation might help physicians know whether or not they have done adequate intervention at the time of application. They demonstrated incorporating impedance along with contact force, power, and time. The predictive value of their lesion indexing approach was quite good. However, further validation in association with an outcome is necessary to look at the incremental value. It also should be noted that this lesion size indexing tool did not necessarily predict steam pop formation, which is more often associated with power.                                 I appreciate everyone's attention to this key and hard-hitting articles that we have just focused on from this past month of cardiac electrophysiology across the literature. Thanks for listening. Now back to Paul. Paul Wang:         Thanks Suraj. You did a terrific job surveying all journals for the latest articles on topics of interest in our field. There's none an easier way to stay in touch with the latest advances. These summaries and a list of major articles in our field each month could be downloaded from Circulation, Arrhythmia, Electrophysiology website. We hope you'll find the journal to be the go-to place for everyone interested in the field. See you next month.    

Dr. Paul Wang:                  Welcome to the monthly podcast "On The Beat" for Circulation, Arrhythmia, and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                                 In our first manuscript this month, Cho and Associates investigate the need for readmission for Dofetilide reloading. The FDA labeling for Dofetilide loading states that Dofetilide must be initiated or reinitiated in hospital with continuous electrocardiographic monitoring.                                                 In this article, the authors retrospectively examine the hospital records for 138 patients admitted for Dofetilide reloading for atrial arrhythmias. Of these 138 patients, 102 were reloaded at a previously-tolerated dose, 30 with a dose higher than a previously tolerated dose, and 2 at a lower dose, with the prior dosage unknown in 4 patients.                                                 In 44 patients, or 31.9%, dose adjustment or discontinuation of Dofetilide was performed, although, torsades de pointes occurred in two patients admitted to increased Dofetilide dosage, no torsades de pointes was observed in patients loaded with the same dose of Dofetilide.                                                 This is 0 versus 6.7% or P = 0.05. In 30 out of 102 patients, 29.4% reloaded at a previously tolerated dose. Dofetilide dose adjustment was required. In 11 out of 30 patients or 36.7% admitted for an increase in dose, a dose adjustment or discontinuation was required.                                                 The authors therefore concluded that dosage adjustments or discontinuation were frequent, and that their observations support the need for hospitalization for Dofetilide reloading. In the next manuscript Tilman Maurer and Associates report a novel superolateral approach to creating a mitral isthmus ablation line.                                                 Because the creation of an endocardial mitral isthmus line with the end point of bidirectional block maybe challenging, the authors examine 114 patients with perimitral annular flutter without a prior mitral isthmus ablation line.                                                 The authors compared the initial group of 57 patients, group A, who underwent catheter ablation using a novel superolateral mitral isthmus ablation line connecting the left sided pulmonary veins with the mitral annulus along the base of the left atrial appendage visualized by selective angiography to another group of patients, 57 patients in groups B undergoing ablation using a conventional mitral isthmus ablation line connecting the left inferior pulmonary vein to the mitral annulus.                                                 The authors found that bidirectional block was achieved in 56 out 57 patients in group A, or 98.2%, and 50 patients in group B, or 87.7%, P=0.06. Ablation from within the coronary sinus was required significantly less for creation of a superolateral mitral isthmus ablation line compared to a conventional mitral isthmus ablation line, 7.0% versus 71.9%, P is less than 0.01.                                                 The need for epicardial ablation from within the coronary sinus in the total length of the mitral isthmus line, 29.3 versus 40.8 millimeters were predictors for unsuccessful bidirectional mitral isthmus blockade. Pericardial tamponade was observed in group A, but not in group B, 5.2% versus 0%, P=0.24.                                                 The authors, therefore, concluded that superolateral mitral isthmus ablation line has a higher acute success rate compared with conventional mitral isthmus ablation line with a low likelihood of needing ablation from within the coronary sinus.                                                 In our next paper, Cronin and Associates examine the relationship between right ventricular pacing frequency, and the incidence of ventricular arrhythmias leading to ICD shock.                                                 Using the altitude database, the authors examined 389 appropriate shocks, and 425,625 transmissions received from 8,435 patients over a mean follow-up of 15.0 months.                                                 Transmissions with 80 to 98% right ventricular pacing were associated with a hazard ratio of 1.56 for an appropriate shock in the subsequent week compared to less than 1% right ventricular pacing, P=0.04 using a time dependent Cox proportional hazard model, however, the authors found that greater than or equal to 98% right ventricular pacing trended towards a lower risk of appropriate shock. Hazard ratio 0.61.                                                 Lifetime cumulative percentage right ventricular pacing was similarly associated with an increased risk of appropriate shocks at 80 to 98% right ventricular pacing, but not greater than or equal to 98% right ventricular pacing.                                                 The authors, therefore, concluded that an increased frequency of right ventricular pacing is associated with an increased risk of appropriate ICD shocks until the right ventricular pacing is greater than or equal to 98%.                                                 In the next manuscript, Wesley O'Neal and Associates examined 12,241 patients from The Atherosclerosis Risk in Communities Study, ARIC study, the association of individual QT components, that is R-wave onset to R-wave peak, R-peak to R-wave end, ST-segment, T-wave onset to T-wave peak, and T-peak to T-wave end with the occurrence of sudden cardiac death.                                                 The authors identified a total of 346 cases of sudden cardiac death identified over a median followup of 23.6 years. The prolongation of the QT interval was associated with a 49% risk of sudden cardiac death. Of the components of the QT interval only the T-wave onset to T-peak component was associated with sudden cardiac death with each standard deviation increase, hazard ratio of 1.19.                                                 The authors found similar results when the QT interval components were included in the same model, thus the authors conclude that the risk of a sudden cardiac death is driven by prolongation of the T-wave onset to T-peak component.                                                 In the next article by Kalliopi Pilichou and Associates, the authors examined copy number variations or CNVs in arrhythmogenic cardiomyopathy patients. The author studied 160 arrhythmogenic cardiomyopathy proband genotype negative for 5 arrhythmogenic cardiomyopathy desmosome genes using conventional mutation screening.                                                 Using multiplex ligation dependent probe amplification, MLPA, 9 heterozygous copy number variations were identified in 11 or 6.9% of the 160 probands. Of these, the authors found that 5 had the least of the entire plakophilin-2 gene to a deletion of only the PRP2 [exon 00:08:45], 1 a deletion of the PRP2 exon 6211, and 1 a PRP2 duplication of the 5 UTR to exon 1. One the desmocollin 2 duplication of exon 7 to 9, and one large lesion of chromosome 18 comprising both DSC2 and desmoglein 2 genes.                                                 All probands were affected by moderate severe forms of disease and 10 or 32% of the 31 family members carrying one of these deletions met the diagnostic criteria for arrhythmogenic cardiomyopathy.                                                 The authors concluded that identifying the copy number variations may increase the yield of genetic testing. In family members carrying the copy number variations, but not displaying the phenotype other factors are likely involved.                                                 In the article by Rahul Samanta and Associates, the authors examined in 7 sheep a mean of 84 weeks post MI, the influence of intramyocardial adipose tissue on scar tissue identification during endocardial contact mapping, the authors found that endocardial electrogram amplitude correlated significantly with intramyocardial adipose tissue.                                                 Unipolar, Right = negative 0.48, bipolar R = negative 0.45, but not correlated with collagen. Unipolar, R = negative 0.36, bipolar, R = negative 0.43. Intramyocardial adipose tissue, dense regions of myocardium were reliably identified using endocardial mapping with thresholds of less than 3.7 millivolts and less than 0.6 millivolts respectively for unipolar, bipolar, and combined modalities.                                                 Unipolar mapping using optimal thresholding remained significantly reliable, an AUC of 0.76. During mapping of intramyocardial adipose tissue confined to punitive scar border zone regions. Bipolar amplitude range of 0.5 to 1.5 millivolts.                                                 The authors concluded that combined bipolar and unipolar voltage mapping with optimal thresholds may permit delineation of intramyocardial adipose dense regions of myocardium following infarction.                                                 In the next article by Kevin Leong and Associates, the authors examined the substraight in electrophysiologic mechanisms that contribute to the characteristic ECG of Brugada syndrome. The authors studied 11 patients with concealed type 1 Brugada syndrome and 2 healthy controls by performing noninvasive electrocardiographic imaging, or ECGI, and ECG recordings during an Ajmaline infusion.                                                 Following Ajmaline infusion the right ventricular outflow tract had the greatest increase in conduction delay and activation recovery interval prolongation compared to the right ventricle or the left ventricle. In controls there was minimal change in the JST point elevation, the conduction delay, or activation recovery intervals at all sites with Ajmaline.                                                 In Brugada syndrome patients, conduction delay in right ventricular outflow tract, but right ventricle or left ventricle correlated with a degree of JST point elevation. Pearson R 0.81.                                                 No correlation was found between the JST point elevation and activation recovery interval prolongation in the right ventricular outflow tract the right ventricle or the left ventricle.                                                  The authors, therefore, concluded that the degree of conduction delay in the right ventricular outflow tract and not prolongation or re-polarization time accounts for the ST or J-point elevation seen in type 1 Brugada syndrome pattern.                                                 In the next article by Jonas Diness and Associates, the authors investigate the role of inhibition with small conductance calcium activated potassium channels in atrial fibrillation termination.                                                 Since these channels are predominately expressed in the atria compared to ventricles, they are a particularly attractive drug target. With a total of 43 pigs atrial tachy pacing was performed until they developed sustained atrial fibrillation that could not be reverted by vernakalant administration.                                                 After the SK channel inhibitor AP14145 was administered, vernakalant resistant AF reverted to sinus rhythm and could not be re-induced by burst pacing. In open chest pigs both vernakalant and AP14145 significantly prolonged atrial refractory of this and reduced AF duration without affecting the ventricular refractory in this or blood pressure.                                                 The authors concluded that SK currents played a role in porcine atrial repolarization and their inhibition by AP14145 demonstrates an arrhythmic affects in a vernakalant resistant porcine model of atrial fibrillation.                                                 In our final article by Padmini Sirish and Associates, the authors examined the role of several ion transporters in action potential duration in cardiac function. The solute carrier SIC26A6, which is highly expressed in cardiomyocytes plays an important role in cardiac intracellular pH regulation.                                                 Using the SIC26A6 knockout mice, the authors found that ablation of SIC26A6 results in action potential shortening, reduced calcium transients, reduced sarcoplasmic reticulum calcium load, and decreased sarcomere shortening in the SIC26A6 knockout cardiomyocytes.                                                 Ablation of the SIC26A6 reduced fractual shortening and cardiac contractility in vivo. Intracelluar pH regulation is elevated in the SIC26A6 knockout cardiomyocytes consistent with the chloride bicarbonate exchange activities of SIC26A6.                                                 The SIC26A6 knockout mice exhibited bradycardia and fragmented QRS complexes supporting the role of SIC26A6 in the cardiac conduction system, therefore, the authors provided evidence that the role of SIC26A6 cardiac electrogenic chloride bicarbonate transporter in ventricular myocytes as well as intracellular pH regulation, excitability, and contractility.                                                 That's it for this month, but keep listening.  Suraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcast "On The Beat." Take it away Suraj. Suraj Kapa:                          Thank you very much Paul and welcome everybody back to "On The Beat," where we'll review hard hitting articles across the electrophysiologic literature. It is my pleasure to introduce you to 15 different articles published in the past month of September across all the journals in cardiovascular medicine.                                                 The first area that we will be focusing on is atrial fibrillation with a specific focus within the realm of anticoagulation, and we refer you to a paper published by [Kurshida Doll 00:16:55], entitled "Factors Associated With Anticoagulation Delay Following New-Onset Atrial Fibrillation," published in The American Journal Of Cardiology on October 15, 2017.                                                 In this publication Kurshida Doll, reviewed the frequency with which there is a delay in introduction of oral anticoagulation after a new diagnosis of atrial fibrillation, and the impact on overall outcomes. In a large electronic medical record they identify incident episodes of atrial fibrillation between 2006 and 2014.                                                 They used the CHADS2 score rather than the CHADS-VASc score to estimate overall risk, and then after this they reviewekud the outcomes of the patients. They found for those patients in whom oral anticoagulation would have been recommended, the median time to initiation was around five days, with an interquartile range of 1 to 43, with by far most patients receiving Warfarin with about 86%.                                                 Interestingly, about 98 strokes occurred between the time of new atrial fibrillation diagnosis, and the actual initiation of oral anticoagulation. Several factors led to this delay in oral anticoagulation including female gender, absence of hypertension, prior falls, and the presence of chronic kidney disease.                                                 However, ultimately, by 6 months over 90% of patients were on oral anticoagulants appropriately, though still a slightly higher proportion appropriately in men than woman.                                                 They noted that most patients with new diagnosis of atrial fibrillation and noted to have an elevated stroke risk started on oral anticoagulation within 1 week. Given these findings it is important to consider how we wait to introduce oral anticoagulation into patients after initial diagnosis given many initial diagnoses may be made by internists, or even in some cases by the patient themselves on a remote monitor or an ambulatory monitor it is important to consider how they are tied into the individual, who would feel most comfortable and who's most apt to prescribe oral anticoagulation.                                                 Changing gears within atrial fibrillation we next move on to cardiac mapping and ablation, and specifically focus on a paper published by Black-Maier et al, in the September edition of "Heart Rhythm" entitled "Risk Of Atrioesophageal Fistula Formation With Contact Force-Sensing Catheters."                                                 While atrioesophageal fistula formation is a relatively rare complication of atrial fibrillation ablation it can be life threatening, contact force catheters for ablation of atrial fibrillation have come into vogue as they are felt to improve procedural effectiveness and potentially reduce complications by improving individual understanding of contact with the myocardium and when contact is excessive.                                                 However, there's been little exploration of the actual risk of atrioesophageal fistula. An [inaudible 00:19:50] from the association they refused the mod database or the manufacturer and user facility device experience database for adverse event reports.                                                 Amongst almost 27,000 device reports they identified a total of 78 atrioesophageal fistula cases. About 1,200 of the reports were related to contact force-sensing catheters and about almost 1,500 were related to non contact force sensing catheters.                                                 Of the 78 atrioesophageal fistula cases reported the vast majority were the contact force-sensing catheters with a total number of 65, or about 5 times more than with non contact force-sensing catheters.                                                 Unfortunately, esophageal temperature increases were only mentioned in about 2.5% of cases in contact force and power settings were not consistently reported in order to come to any conclusions. They noted the overall mortality with atrioesophageal fistula in this population was around 56%, with really the vast majority surviving as a result of surgical repair as apposed to stenting or no intervention.                                                 While this data is somewhat skewed because it's based on self reported data by proceduralists, who are reporting back to the mod database, it is important to consider whether or not there is actually an increase complication rate associated with contact force-sensing catheters as these catheters do reflect a fundamentally different catheter than the non contact force-sensing catheters routinely used due to changes in the stiffness, and the mechanics of the catheter itself.                                                 It is important to consider when using any new catheter with any new options for monitoring, or that might alter the stiffness, or other mechanical properties of the catheter, whether or not application of similar power settings are relevant.                                                 While the data is potentially skewed in the status set it will be important to consider it going forward as to whether or not there are implications of some increased risk of complications, and how to mitigate these by altering our contact force and power setting decision making.                                                 Further study will be required in order to better understand these data and the implications. I would refer the readers also to an article published by [inaudible 00:22:02] in circulation where they reviewed the mechanism of atrioesophageal injury and also to another publication published in The Journal Of Cardiovascular Electrophysiology this past month by [inaudible 00:22:11], where they did a meta analysis of the overall benefit of contact force related catheters over non contact force related catheters.                                                 In that paper they demonstrated that based on this meta analysis there seems to be an overall benefit in terms of outcomes in contact force-sensing catheters without a difference in procedural complications. However, I would refer the reader to the fact that there are very limited randomized studies comparing contact force versus non contact force catheters.                                                 Next, also within the realm of cardiac mapping and ablation we reviewed a publication by Haldar, et al., entitled Resolving Bipolar Electrogram Voltages During Atrial Fibrillation Using Omnipolar Mapping, published in the last edition of Circulation Arrhythmia Electrophysiology. Also, reviewed by Dr. Wang in last months podcast.                                                 The importance of this article lays in an improved understanding of what we mean when we talk about voltage or substraight mapping. In his paper, Haldar, et al., tried to understand better what the bipolar electrogram might actually refer to when comparing traditional bipolar mapping versus omnipolar mapping.                                                 This becomes important as we consider a low voltage guided substraight modification for not just atrial fibrillation ablation, but also potentially for ventricular arrhythmia ablation. They sought to compare the use of peak-to-peak voltage for assessment of bipolar voltage with omnipolar peak-to-peak voltages in both sinus rhythm and atrial fibrillation.                                                 They demonstrated that in canines vertical orientation of a catheter relative to the underlying tissue consistently resulted in a higher bipolar voltage in both sinus rhythm and atrial fibrillation. Furthermore, they show that the max obtained ominipolar voltage were consistently larger than multi-horizontal and vertical voltages in both rhythms.                                                 Vector field analysis of these wave fronts during atrial fibrillation in particular, demonstrated the omnipolar electrograms can account for a collision in fractionation, and required an electrogram of voltages independent of these effects. Thus, they suggested that the omnipolar electrograms can use maximum voltages, and can separate the influence from directional factors, collision, or fractionation especially when compared with contemporary bipolar techniques.                                                 The implications of the study are several. First off, when performing substraight mapping we traditionally use what we can in terms of trying to get appropriate bipolar signal analysis. However, catheters have significantly evolved since the early studies of bipolar voltage mapping in terms of establishing voltage cutoffs.                                                 There are many different multipolar catheters with varying interelectrode spacing, but sometimes prefer parallel orientation to the underlying myocardium as opposed to vertical orientation. The fact that bipolar voltage can significantly vary based on both orientation of the catheter as well as the rhythm is important when considering whether a substraight actually exists in a specific location or not, and what "Normal voltage cutoffs," where specific patients should be."                                                 When we consider novel catheters with increasing complex design including introduction of mini electrodes as well as omnipolar electrodes, it is important to consider whether an assessment of "Normal voltage," should be the same. Further study will be required to better understand how to best analyze these results.                                                 Moving to a different form of management in atrial fibrillation we will next refer you to a paper by Borris [Madal 00:25:44] published in this last month's edition of Heart Rhythm, entitled Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation, 1-Year follow-up outcome data of the EWOLUTION  trial.                                                 The EWOLUTION trial was a prospective multi center registry looking at the outcomes of WATCHMAN patients, who had indication for closure based on European society of cardiology guidelines. They sought to evaluate a 1 year followup of these patients.                                                 The baseline CHADS-VASc score was on average about 4-1/2 with a mean age of over 73 years. Almost a third of the patients had prior transient ischemic attach or ischemic stroke. They noted that the vast majority of the patients had a successful WATCHMAN implantation with a 1,005 out of 1,025 patients having successful implantation, with only 3 of these 1,005 patients having any leak greater than 5 millimeters.                                                 The majority up to 87% had T-followup at least once after initial implantation. Interestingly, the vast majority only used antiplatelet therapy with only 8% having vitamin K antagonist used in the post WATCHMAN implantation period.                                                 There was a reasonably high mortality of 10% in the first year after implantation, though this was felt to typically reflect advanced age and other comorbidities. Also, interestingly almost 4% of patients had thrombus on their device, which was independent of the drug regimen used. In other words whether antiplatelet therapy or vitamin K antagonists.                                                 Overall, the ischemic stroke rate was relatively low at 1.1%, with a relative risk of 84% versus estimated historical data, and also with a relatively low major bleeding rate of only 2.6% and this predominately being non-procedure of device related.                                                 Thus, they concluded that LA closure with the WATCHMAN device had a high implant and sealing success, and it appeared to be safe and affective in reducing ischemic stroke risk given that the relative incidence was only 1.1%, despite the fact that the vast majority were not actually even using oral anticoagulation.                                                 There are trial ongoing in the United States to evaluate whether or not patients can be safely kept off of oral anticoagulation in the peri-implant period as in some countries standard of care is to place them on anticoagulants in the immediate post implantation period.                                                 However, two other things need to be noted in this real world analysis of outcomes with WATCHMAN. Almost 10% or 1 out of 10 patients died within 1 year of followup, thus whether or not better patient selection is required to understand those patients will receive maximal benefit from this invasive procedure might be considered.                                                 Further, more almost 4% had device related thrombus. What this means in terms of stroke risk especially over longterm followup needs to also be considered. I think overtime we'll get better understanding of what those risks might be for an endocardial system for a left atrial appendage occlusion.                                                 But, staying within the realm of stroke risk in atrial fibrillation, we next review the article by King, et al., published in The Journal Of American College Of Cardiology, in the September 2017 edition entitled, Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.                                                 Cardiac MRI to evaluate late gadolinium enhancements suggesting regional cardiac fibrosis and atrial fibrillation is slowly taking steam, but primarily as a method of assessing potential efficacy of atrial fibrillation ablation with greater amounts of delayed enhancement potentially suggesting an overall lower risk, or a lower likelihood of success of atrial fibrillation ablation.                                                 King, et al., sought to evaluate in a retrospective cohort study regarding the risk of cerebrovascular and cardiovascular major events associated with a degree of delayed enhancement in MRI. They reviewed 1,228 patients undergoing cardiac MRI to assess left atrial fibrosis between 2007 and 2015.                                                 They then staged these patients and stratified them according their [Utah 00:29:45] stage, which had been previously recorded for the degree of fibrosis seen. They demonstrated on followup that there was a significantly higher incidence of major cardiovascular and cerebrovascular events associated with higher degrees of late gadolinium enhancement with a relative risk ratio of about 1.67.                                                 However, the only individual component of these outcomes that remains significantly associated with advanced gadolinium enhancement was actually stroke or TIA, with a hazard ratio of 3.94, thus they concluded that severe LA late enhancement is associated with increased cerebrovascular events principally.                                                 This study is important in that it highlights another potential risk factor that may need to be considered when risk stratifying patients for their risk of stroke. We recognize that even some paroxysmal patients can have extensive left atrial fibrosis, and some persistent patients might not have a ton of atrial fibrosis.                                                 Whether this can further help risk stratified patients in terms of overall stroke risk, and might identify and help characterize low risk patients further needs to be considered.                                                 One of the key features of this evaluation needs to be also the mechanism. In theory patients with greater endocardial injury of the atrium might be more prone to clot formation, and thus it may seem reasonable to expect indeed when we have more left atrial fibrosis as suggested by delayed enhancement on MRI. There may in fact be a higher greater cerebrovascular event rate.                                                 Finally, changing gears a little bit within the realm of risk stratification and management for atrial fibrillation we focused on autonomics and specifically a publication by Stavrakis et al., in the last month edition of Jack Clinical Electrophysiology, entitled Low Level Vagus Nerve Stimulation Suppresses Postoperative Atrial fibrillation And Inflammation In A Randomized Study.                                                 The group, headed up by Sonny [Poe 00:31:42] have previously published on both tragus stimulation as well as low level of vagus nerve stimulation in patients undergoing atrial fibrillation ablation. In this particular study they sought to evaluate whether or not implantation of a low level of vagus nerve stimulator during cardiac surgery could reduce the risk of postoperative atrial fibrillation.                                                 They sutured a bipolar wire to the vagus nerve preganglionic fibers along the lateral aspect of the superior vena cava at the time of surgery. They then performed high frequency stimulation of 50% below the threshold for slowing the heart rate for 72 hours, and those randomized to the vagus nerve stimulation group.                                                 The secondary group was a sham cohort. They demonstrated amongst the 54 patients randomized to either group that the frequency of postoperative atrial fibrillation was almost a third in the low level of vagus stimulation group when compared with the control group.                                                 Interestingly, their frequency of atrial fibrillation was not only lower, but the level of inflammatory markers also decreased with both serum tumor necrose factor alpha and interleukin 6 levels being significantly lower in the low level vagus nerve stimulation cohorts.                                                 In line with prior data from atrial fibrillation ablation these data were suggesting that low level of vagus nerve stimulation can suppress postoperative atrial fibrillation and attenuate the inflammatory response.                                                 Also, in this past month there was a paper by [Yoo 00:33:09] et al., in The Journal Of The American Heart Association, specifically looking at the use of vagus nerve stimulation at the level of the tragus in patients with obstructive sleep apnea associated atrial fibrillation.                                                 Similar to prior work form the Oklahoma group, they demonstrated that in fact there is a beneficial effect on reduction of atrial fibrillation, and this is primarily mediated through attenuation of autonomic factors that mediate obstructive sleep apnea related atrial fibrillation.                                                 Moving away from atrial fibrillation, we next delve in cellular physiology first starting with an article published in Nature Scientific Report this past month, on very low density lipoprotein in metabolic syndrome, and how it modulates gap junctions and slows cardiac conduction.                                                 In the past year there have been multiple studies regarding specific cell types and how they might interplay with cardiac fibrosis, and risk of conduction slowing. In this publication we had all reviewed the effect of very low density lipoproteins, and their effect on cardiac conduction in, in vitro models.                                                 They demonstrated that primarily through down regulation of [conexion 00:34:21] 40 and conexion 43, very low density lipoproteins have significant impact on cardiac conduction with increased prolongation of the P-wave, PR-intervals, QR restoration, and QTC intervals.                                                 Thus, they concluded that very low density lipoproteins may contribute to the path of physiology of both atrial fibrillation and ventricular arrhythmias that can be seen in metabolic syndrome. This report is important because it highlights the fact that we can actually see other cell types including LDL causing a significant reduction in cardiac conduction and thus mediating arrhythmogenesis.                                                 In fact there was one other paper published just a couple weeks prior also in The Nature Of Scientific Reports by [Lee 00:35:04] et al., entitled Human Electronegative Low-Density Lipoprotein Modulates Cardiac Repolarization Via LOX-1-Mediated Alteration Of Sarcolemmal Ion Channels.                                                 They showed that LDL can actually result in QTC prolongation in patients with ischemic heart disease by specific mechanisms involving LOX-1. Recognition of the mechanisms behind which less traditional factors such as VLDL or LDL may mediate alterations in cardiac conduction are important when we consider our potential novel targets for treatment of arrhythmias in patients whether for prevention or for treatments.                                                 In light of this attempt to identify novel targets we next move on to another paper in the realm of cellular electrophysiology published by [Toib 00:35:52] et al., in The American Journal of Physiology, Heart and Circulatory Physiology, entitled Remodeling Of Repolarization And Arrhythmia Susceptibility In A Myosin-Binding Protein C Knockout Mouse Model.                                                 In hypertrophic cardiomyopathy there might be multiple mechanisms that might lead to increased risk of ventricular arrhythmias. These might be scar related due to the fact that patients can burn out from the hypertrophic cardiomyopathy overtime and get both endocardial, epicardial, and mid myocardial fibrosis, but what are the mechanisms that might mediate the development of ventricular arrhythmias and hypertrophic cardiomyopathy remain to be elucidated, and there's been very limited evaluation of the effect of repolarizing potassium currents on this risk.                                                 Thus, Toib, et al., studied myosin-binding protein C knockout mice to look at what happens with repolarizing potassium currents in his cohorts. They demonstrated that in these knockout mice there was a prolongation in the corrected QT interval when compared to the wild type mice with overt ventricular arrhythmias.                                                 They also demonstrated that there is action potential prolongation associated with a decrease for polarizing potassium currents, and a decreased MRNA levels of several key potassium channels subunits, thus, they concluded that in this specific subtype of hypertrophic cardiomyopathy needed by myocin combining protein C mutations that part of the ventricular arrhythmia risk might be due to a decrease in polarizing potassium currents in turn leading to increase in action potential and QT interval.                                                 The reason that this particular finding is important is in my highlight drug selection in specific types of hypertrophic cardiomyopathy. In my postulate for example the class 3 antiarrythmics drugs might actually increase risk in some subtypes of hypertrophic cardiomyopathy due to down regulation of potassium channel subunits.                                                 Consideration of this is critical when best evaluating how to mange and treat these patients. Changing gears to another method of channelopathy we focus within the realm of genetic channelopathies and specifically on Brugada syndrome.                                                 In this last month's edition of Heart Rhythm, Sierra, et al., published their series of longterm prognosis of drug induced Brugada syndrome. They reviewed a consecutive cord of 343 patients with drug induced Brugada syndrome, and compared their outcomes with 78 patients with a spontaneous type 1 pattern.                                                 The mean age of patients was around 41 years. Interestingly, about 4% of the patients had a clinical presentation of 7 cardiac deaths, and 25% had a clinical presentation of syncope. However, the majority of the patients were asymptomatic, around 71%.                                                 Most of the patients were female amongst the drug induced Brugada syndrome cohort. They demonstrated that there were less ventricular arrhythmias both induced string and electrophysiology study, and seen over followup of up to 62 months in the drug induced Brugada syndrome cohort as compared with the spontaneous type 1 cohort.                                                 Overall, the event rate in drug induced Brugada syndrome was 1.1% of [person year 00:38:54] versus 2.3% of person year in patients with spontaneous type 1 pattern.                                                 They suggested that presentation of sudden cardiac death or inducable ventricular arrhythmias at the time of VP study were independent risk factors associated with arrhythmic events in drug induced Brugada syndrome. However, if a patient was asymptomatic and had no inducible ventricular arrhythmias they had a significantly better prognosis with drug induced Brugada syndrome over a spontaneous type 1 pattern.                                                 Thus, they concluded that even in drug induced Brugada syndrome sudden cardiac death is possible. However, in asymptomatic patients without a prior clinical presentation of sudden cardiac death or inducible ventricular arrhythmias during electrophysiology study, they may be relatively safer than their spontaneous type 1 counterparts.                                                 This study highlights the importance of stratification of patients into the mechanism of how their genetic channelopathy presents whether as a spontaneous finding or as a finding in the setting of other events. Further prospective analysis, however, is needed to best guide how to manage these patients and in whom to put a defibrillator as I would note that almost 37% of these patients actually had an ICD placed with the vast majority without incident events.                                                 Speaking of implantable devices we next move to the realm of ICD pacemaker and CRT, and specifically we review the publication by Samar, et al., published in Jack Clinical Electrophysiology this past month on the diagnostic value of MRI in patients with implanted pacemakers and implanted cardiover defibrillators across the population.                                                 Does the benefit justify the risk of proof of concept study? Increasingly, MRIs are being done in patients with even Legacy defibrillators and permanent pacemakers. However, when assessing the benefit versus the risk it's important to understand did the MRI actually change outcomes, and this was a specific question that the authors tried to answer.                                                 They took patients with conventional or Legacy pacemakers or ICDs, and tried to evaluate what the actual benefit was on those patients in whom an MRI was done. They specifically asked four questions, one, did the primary diagnosis change, two, did the MRI provide additional information to the existing diagnosis, three, was the pre-MRI or tentative diagnosis confirmed, and four, did the patient management change?                                                 They noted there were no safety issues encountered in any of the 136 patients an MRI was performed. In 97% it was felt that MR added value to the patient diagnosis and managements, with 49% of investigators feeling that MR added additional valuable information to the primary diagnosis, and in nearly a third the MR actually changing the principle diagnosis and subsequent management of the patient.                                                 Increasing evidence suggesting that MRI can be safely performed even in Legacy pacemakers and ICDs, and the fact the MRI can wield important evidence related to diagnostics needs to be taken into consideration as investigators and other centers try to identify methodologies for safely performing MRIs in these patient cohorts.                                                 It seems thus far like MRI might justify risk of these procedures under controlled settings. Next, we move also within the realm of implantable cardioverted defibrillators, but to a different assessment published by Kawada et al., in this past months issue of Heart Rhythm where they sought to evaluate the comparison of longevity in clinical outcomes of implantable cardioverted defibrillator leads among manufacturers.                                                 They specifically sought to assess the longevity of [Lynox 00:42:35] SSD by [Atronic 00:42:36] leads compared with Sprint Fidelis by Matronic, Sprint Quattro by Matronic, and Endotac Reliance by Boston Scientific Leads. The reasoning for this was early failure of some of the biotronic Lynox leads has been reported. Thus, they retrospectively reviewed patients undergoing implantation with these different lead approaches between 2000 and 2013.                                                 They noted failure rates of the Lynox versus Spring Fidelis versus Endotac leads where 3.2% for a year, versus 3.4% for a year, versus 0.61% for a year respectively. No lead failure was notable with a followup [inaudible 00:43:13] in Sprint Quattro leads, thus, they felt that the survival probability of Lynox leads was comparable to Sprint Fidelis leads, and lower than that of Endotac or Sprint Quattro leads.                                                 They found that age was the primary predictor of Lynox lead failures with the patients less than 58 years old had significantly increased risk of lead failure compared with those greater than 58 years old, thus, they concluded that this was a first description of a lower survival rate for Lynox leads in an aging population.                                                 Early identification of leads that might be at risk of failure is critical in patient risk stratification. The finding that there might be other leads that might be at risk of failure highlights the importance of close monitoring of these leads in contribution to register data.                                                 I would note that within this study that it was primarily done at one center and the vast majority of patients actually received Lynox leads. Thus, further evidence was clinically required for more centers to understand what the mechanism of this risk is, and also whether the risk is born out consistently across multiple centers particularly because the vast minority got the one lead, but didn't have any lead failure encountered for.                                                 Further, speaking about defibrillators we focus on the different mechanism of failure, and specifically the publication by [Thogersen 00:44:38] et al., published in last months' edition of Circulation And Arrhythmia Electrophysiology entitled Failure To Treat Life Threatening Ventricular Tachy Arrhythmias In Temporary Implantable Cardioverted Defibrillators Implications For Strategic Programming.                                                 In this publication they did not so much focus on lead failure, but the failure the ICD due to potential strategic programming decision making on appropriately treating ventricular tachy arrhythmias. Their current consensus recommendations as far as using a generic rate threshold between 185 and 200 beats per minutes in primary prevention ICD patients, thus, they sought to determine in the case series what the relationship between program parameters and failure of modernizing ICDs to treat for VF actually worked.                                                 Between 2015 and 2017 at four institutions they reviewed cases where normally functioning ICDs failed to deliver timely therapy for VF. There were a small number of patients noted fitting this criteria with only 10 ambulatory patients. Five actually died from their untreated VF, whereas four had cardiac arrests through a witness requiring external shocks, and one was ultimately rescued by a delayed ICD shock.                                                 The main reason that they were not appropriately treated were that the ventricular fibrillation event did not satisfy the programmed detection criteria in nine out of ten patients. Seven of the patients had the slowest detection rates consistent with generic recommendations, but were never tested in the peer review trial for the manufacturers ICDs.                                                 Namely, the decision making on the appropriated generic rate threshold was tested on specific manufacturers ICDs, but didn't apply the decision making on programming on other manufactures ICDs. In some cases manufacturers specific factors were interacting with fast detection rates to withhold therapy such as enhancement in MIC wave oversensing.                                                 Thus, they demonstrated that in this population untreated VF despite recommendation programming, accounted overall for 56% of sudden deaths and 11% of all deaths in the overall cord of patients during the study period.                                                 Thus, over half of the cases where sudden death occurs in patients with ICDs appears to be due to untreated VF despite recommended programming. Thus, they concluded that these unanticipated interactions or complex decision making regrading generic program of parameters might in part lead to withholding of therapy inappropriately in ventricular fibrillation.                                                 This publication highlights the importance of thoughtful decision making when translating evidence based detection parameters both between manufacturers and applying them across individual patients.                                                 While the overall number of patients is quite low, mainly only ten patients who were affected by this event, the number of patients dying as a result of it is fairly high in terms of a percentage with 56% of sudden deaths occurring as a result of untreated VF from variation from recommended programming.                                                 Closer attention needs to be paid to understanding how to better assess which patients would benefit from the current generic rate thresholds as opposed to who will be harmed by it. It is possible that one size fits all approach will always result in some harm to some, while benefit to others as potentially cutting down the lower rate cutoff in some patients might lead to inappropriate therapies, which might be as life altering as untreated VF in many patients.                                                 Finally, keeping within the realm of defibrillation we review an article by [Layva 00:48:24] et al., published in last month's edition of The Journal of American College of Cardiology entitled Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.                                                 There are several recent studies that have started to cast doubt on what the incremental benefit of defibrillation adage cardiac resynchronization therapy actually is in nonischemic cardiomyopathy.                                                 However, we also know that in patients with scar noted on MRI that there can be an increased risk of ICD therapy, thus, part of the difficulty that some individuals have is how we define the nonischemic cardiomyopathy cohorts. Namely, is all nonischemic cardiomyopathy crated equal and we can better risk stratify this population to subtypes some of whom might benefit from primary correction defibrillators and some of whom might not?                                                 Thus, in this study they aimed to determine whether CRTD is superior to CRTP in patients with nonischemic cardiomyopathy based on the presence or absence of left ventricular midwall fibrosis detected by cardiac magnetic resonance.                                                 There were a total of 68 patients who had midwall fibrosis, and 184 patients who had not, and all of them underwent the evaluation prior to CRT implantation. They noted that the presence of midwall fibrosis was an independent predictor of total mortality with a hazard ratio of 2.31 as well as total mortality or heart failure hospitalization.                                                 This sudden cardiac hazard ratio was about 3.75 with an increased risk attributable to the presence of midwall fibrosis. They also noted that total mortality or heart failure hospitalization, and total mortality or hospitalization for major adverse cardiac events was significantly lower in patients with CRT defibrillator than with CRT pacemaker in those with midwall fibrosis, but not in those without midwall fibrosis.                                                 These findings highlight that in some patients with nonischemic cardiomyopathy CRTD may be superior to CRTP, though these might be guided by the presence of abnormal substraights. The evaluation of what nonischemic cardiomyopathy means in an individual patient needs to be closely considered.                                                 Nonischemic cardiomyopathy is a blanket term for all those patients who do not have an ischemic cardiomyopathy and who may or may not have been fully evaluated for discrimination of another type of myopathy such as infiltrated myopathies for example sarcoidosis.                                                 The value of cardiac magnetic resonance imaging is being increasingly understood as it applies to both risk stratification, nonischemic cardiomyopathy, as well as the value in decision making as far as treatment of these patients. In a recent publication published this past month as well in Jack Electrophysiology, by [inaudible 00:51:13], et al., they reviewed the efficacy of implantable cardioverted defibrillator therapy in patients with nonischemic cardiomyopathy based on a meta analysis of existing trials.                                                 They demonstrated in a meta analysis of randomized controlled trials that compared to medical therapy ICD has significantly improved survival among patients with nonischemic cardiomyopathy with an injection fraction of less and equal to 35%. However, CRT defibrillator overall was not associated with statistically significant mortality death when compared to CRT pacemaker.                                                 These findings are actually complimentary to each other, but need to be considered in context. One of the indications for the recently published Danish study was the fact that not only is CRT being increasingly utilized appropriately in patients with nonischemic cardiomyopathies, but also guideline directed medical therapy has improved over the course of the last several years since the initial trials of defibrillator therapy as primary prevention.                                                 Furthermore, the trial was actually powered based on a 25% reduction in overall events. Thus, even if there's a smaller benefit it would not necessarily be powered to identify if this is statistically significant. One issue as stated is the fact that nonischemic cardiomyopathy might be a milieu of different causes in individual patients. Some of whom might be at high risk for sudden cardiac death and some of whom might not.                                                 The publication by Levya, et al., highlights that better attempts at risk stratification on the basis of either MRI or other modalities might be important in helping us further assess who actually benefits from ICD, however, when mixing in prior trials with more recent trials that existed at different areas of medical therapy, and different areas of appropriate use of devices such as CRT it is critical to consider whether or not the same cutoffs, the same power calculations still apply.                                                 It is doubtless that defibrillator therapy is needed in many patients with both ischemic and nonischemic cardiomyopathy even with improved therapies for these patients otherwise. However, this multitude of publications coming out to improve our assessment of the utility of ICDs should not necessarily call into question of whether or not ICDs are merited at all, but should call into question whether we understand and have come to the best form of risk stratification for those patients who would most benefit, and thus this is an opportunity for us to identify those patients better.                                                 Next, we will move to the realm of supraventricular tachycardia's and specifically an article published by [Yang 00:53:41], et al., in the last month's edition of Heart Rhythm, entitled Focal Atrial Tachycardia's From The Parahisian Region, Strategies From Mapping And Cather ablation.                                                 With focal atrial tachycardia's from the parahisian region can potentially be targeted from multiple different regions, the right atrial septum, the noncoronary cusp, and the right middle septum. However, the optical mapping and ablation strategy for these arrhythmias remains unclear, and thus they sought to investigate electrophysiology characteristics in optimal ablation sites for parahisian [inaudible 00:54:10] from these different areas.                                                 They reviewed 362 patients with atrial tachycardia's undergoing catheter ablation. They did DCG analysis and electrophysiology studies extensively on these patients. Overall, 91 patients had a parahistian origin. An ablation was successful in a majority of these up to 94.5%.                                                 The majority of these patients had their AT successfully eliminated from the noncoronary cusp with about 44 of the 91 having it targeted from this region, with the remaining 23 from the right atrial septum, and 19 from the right middle septum. They noted those who had an earliest potential at the distal HIS catheter tended to have their site of origin more successfully ablated from the noncoronary cusp.                                                 However, those with a greater [inaudible 00:54:55] in the proximal HIS catheter tended to more likely have successful ablation from the right atrial septum or right middle septum. The mean timing of the A potential in differentiating right and middle septum ATs from right atrial septum ATs, was that they attended to be later in right middle septum ATs, than right atrial septum ATs, or noncoronary cusp ATs.                                                 They noted that for atrial tachycardia's arising from the right atrial septum and right middle septum, an A to V ratio less than 1.22 predicted safe and successful ablation with a sensitivity of 88.4% and the specificity of 91.7%. Thus, they concluded that activation sequence and timing of the A and HIS catheter could provide clues for where the most likely successful site of ablation would occur for parahisian tachycardia's.                                       

Dr. Paul Wang :                 Welcome to the monthly podcast On the Beat for circulation, arrhythmia and electrophysiology. I’m Dr. Paul Wang editor in chief with some of the key highlights from this month’s issue. We’ll also hear from Dr. Suraj Kapa reporting on new research for the latest journal articles in the field.                                                 The first article in this month's issue is by Yoav Michowitz and Associates who examine the morphological ECG characteristics of left posterior fascicular ventricular tachycardia and differentiated from right bundle branch block and left anterior hemiblock aberrancy. 183 ECGs with left posterior fascicular ventricular tachycardia in patients who underwent ablation were identified using a systematic Medline search were examined and compared to 61 ECGs with right bundle branch block in left anterior hemiblock aberrancy with no obvious cardiac pathology by echocardiography.                                                 Using four variables including atypical right bundle branch block like V1 morphology, positive QRS in aVR, V6R greater than S ratio of less than one and QRS less than or equal to 140 ms, a prediction model was developed that predicted posterior fascicular ventricular tachycardia with a sensitivity of 82% and a specificity of 78%. Patients with three out of four positive variables had a high probability of having left posterior fascicular ventricular tachycardia whereas patients with less than or equal to one positive variable always had right bundle branch block plus left anterior hemiblock.                                                 In the next article, Anna Thøgersen and associates describe a case series of 10 patients in whom implantable cardioverter defibrillators failed to treat ventricular tachyarrhythmias. The authors examine whether consensus derive generic rate threshold cutoffs between 185 and 200 beats per minute were employed in this case series. In nine patients, ventricular fibrillation did not satisfy program detection criteria. Five patients died with untreated ventricular fibrillation, four had cardiac arrest requiring external shocks and one was rescued by a delayed ICD shock. Seven of these patients had slowest detection rates that were consistent with generic recommendations but not tested in a peer review trial for their manufacturer’s ICDs.                                                 In the reported cases, manufacturer specific factors interacted with fast detection rates to withhold therapy including strict ventricular fibrillation episode termination rules, enhancements to minimize T-wave over sensing and features that restrict therapy to regularly rhythms in VT zones. Untreated ventricular fibrillation despite recommended programming accounted for 56% of the deaths and 11% of all of deaths. The authors concluded that complex and unanticipated interactions between manufacturer specific features and generic programming can prevent therapy for ventricular fibrillation.                                                 In the next article, Miguel Rodrigo and associates describe from 17 simulations of atrial fibrillation, atrial flutter and focal atrial tachycardia the ability to understand signal processing that can affect identification of reentrant activity using electrograms, body surface potential mapping and electrocardiographic imaging ECGI phase maps. Reentrant activity was identified by singularity point recognition and raw signals and in signals after narrow band pass filtering at the highest dominant frequency.                                                 Reentrant activity was identified without filtering in 60% of unipolar records but filtering was required to increase reentrant activity detection from 1% to 62% in bipolar recordings. The filtering resulted in residual false reentrant activity in about 30% of bipolar recordings. The authors concluded that rotor identification is accurate and sensitive and does not require additional signal processing in measured or noninvasively computed unipolar electrograms while bipolar electrograms and body surface potential mapping do require highest dominant frequency filtering in order to detect rotors at the expense of a decrease specificity.                                                 In the next article, Raymond Yee and associates examine the ability of a new automated antitachycardia pacing algorithm to reduce ICD shocks. The new automated ATP algorithm was based on electrophysiologic first principles and prescribed the ATP sequences in real time using the same settings for all patients. In 144 patients who had dual chamber or CRT ICDs as well as a history of one or more ICD treated VT or VF episodes or a recorded sustained monomorphic ventricular tachycardia episode. Detection was sent to ventricular fibrillation interval detection of 24 out of 32 ventricular tachycardia interval detection of 16 or greater in a fast VT zone of 242 to 320 ms.                                                 There were 1,626 treated episodes in 49 patients over 14.5 month’s follow up. Data logs permitted adjudication of 702 episodes including 669 sustained monomorphic ventricular tachycardia episodes, 20 polymorphic ventricular tachycardia episodes, 10 SVT episodes and three mal sensing episodes. The novel automated antitachycardia pacing algorithm terminated 39 out of 69 episodes or adjusted 59% of the sustained monomorphic ventricular tachycardia events in the fast VT zone, but 509 out of 590 or 85% adjusted in the VT zone and 6 out of 10 in the VF zone. No SVTs were converted to VT or VF and no anomalous ATP behavior was observed. The authors concluded that this new automated ATP algorithm could be used safely in all zones without need for individualized programming.                                                 In the next study Pablo Ávila and associates studied the incidence and clinical predictors of atrial tachycardias in adults in a cohort of 3,311 patients with congenital heart disease. Prospectively followed in a tertiary center for 37,607 person years. The study patients were divided into three categories; 49% simple, 39% moderate and 12% complex congenital heart disease. In this cohort, 153 or 4.6% of patients presented with atrial tachycardia. The atrial tachycardia burden was highest in complex congenital heart disease such as single ventricle 22.8% or D-TGA 22.1%.                                                 The authors found that univentricular physiology, previous intracardiac repair, systemic right ventricle, pulmonary hypertension, pulmonary regurgitation, pulmonary AV valve regurgitation and pulmonary and systemic ventricular dysfunction were independent risk factors for developing atrial tachycardia. At the age of 40 years, atrial tachycardia free survival in patients with zero risk factors was 100%. With one risk factor, it was 94%. With two risk factors was 76% and three or more risk factors was 50%. These authors confirm these findings in a validation cohort.                                                 In the next article, Khidir Dalouk and associates compare clinical outcomes between ICD patients followed up in a telemedicine videoconferencing clinic and a conventional in person clinic. In this retrospective study, the authors compared time to first appropriate ICD therapy, time to first inappropriate ICD therapy, time to first shock and overall survival. The authors studied 287 patients in the telemedicine videoconferencing clinic group and 236 patients in the conventional in person clinic over mean follow-up duration of 4.8 years. The authors found that telemedicine videoconferencing clinic was not inferior to in person follow-up for the pre-specified outcomes.                                                 In the next article, Elisabeth Mouws and associates studied the epicardial breakthrough waves in sinus rhythm possibly giving insight to the arrhythmogenic substrate in atrial fibrillation. In 381 patients with ischemic or valvular heart disease, intraoperative epicardial mapping with intro electro distance of 2 mm was performed of the right atrium, Bachmann’s bundle, the left atrioventricular groove and the pulmonary vein area. Epicardial breakthrough waves were referred to as sinus node breakthrough waves if they were the earliest right atrial activated site. A total of 218 epicardial breakthrough waves and 57 sinus node breakthrough waves were observed in 168 patients or 44%.                                                 Epicardial breakthrough waves mostly occurred at the right atrium and 48% at the left atrioventricular groove and 31% followed by Bachmann’s bundle and 12% and the pulmonary vein area and 9%. Epicardial breakthrough waves occurred most often in ischemic heart disease patients 49% to valvular patient's 17%. Epicardial breakthrough wave electrograms most often consisted of double or fractionated electrograms seen in 63%. Fractionated epicardial breakthrough wave potentials were more often observed at the right atrium or Bachmann's bundle. The authors concluded that epicardial breakthrough waves are present in over a third of patients possibly indicating muscular connections between the endocardium and epicardium that may enhance the occurrence of epicardial breakthrough waves during atrial fibrillation promoting AF persistence.                                                 In the next article, Shouvik Haldar and associates compare horizontal and vertical orientation bipolar electrograms with novel omnipolar peak to peak voltages in sinus rhythm and atrial fibrillation using a high density fixed multi-electrode plaque placed on the epicardial surface of the left atrium in dogs. Bipolar orientation had significant impact on bipolar electrogram voltages obtained either in sinus rhythm or atrial fibrillation. Omnipole Vmax values were 99.9% larger than both horizontal or vertical electrograms in sinus rhythm in larger than horizontal or vertical electrograms in atrial fibrillation.                                                 Further vector analysis of omnipole electrograms showed that omnipolar electrograms can record electronic voltage unaffected by collision and fractionation. The authors concluded that omnipolar electrograms can attract maximal voltages from AF signals which are not influenced by directional factors, collision or fractionation compared to contemporary bipolar techniques.                                                 In our final article for the month, Pauline Quenin and associates examine the efficacy of screening in relatives of subjects who died suddenly. The authors provided clinical screening to 64 families who experienced unexplained sudden cardiac death before age 45 in a prospective multicenter registry. The diagnosis was established in 16 families, 25% including Brugada syndrome, long QT syndromes, dilated cardiomyopathy and hypertrophic cardiomyopathy. The diagnostic yield was mainly dependent on a number of screen relatives with 3.8 screen relatives in the diagnosed family versus 2.0 in the non-diagnosed families rising to 40% with at least three relatives.                                                 It additionally increased from 9% to 41% when both parents were screened. Diagnostic performance was also dependent on the exhaustiveness of the screening. 70% of complete screening versus 25% with incomplete screening with 17 Brugada syndrome and 15 long QT syndrome diagnoses based on pharmacologic tests. The authors concluded that even without autopsy, familial screening after sudden death in young patients is effective greatly increasing the likelihood of diagnosis in families.                                                 That's it for this month but keep listening. Suraj Kapa will be surveying all journals for the latest articles on topics of interest in our field. Remember to download the podcast On the Beat. Take it away Suraj. Suraj Kapa:                          Thank you Paul. It is my pleasure to welcome everybody back to our continued series of On the Beat articles from across the electrophysiology literature especially selected to highlight their potential importance in terms of either current or future practice within the realm of cardiac electrophysiology. Again, my name is Suraj Kapa and it is my pleasure to walk us through a variety of hard-hitting articles.                                                 Today we’ll be starting within the realm of atrial fibrillation specifically as it relates to cardiac mapping and ablation. The first article was by Iwasawa et al entitled Temperature Controlled Radiofrequency Ablation for Pulmonary Vein Isolation in Patients with Atrial Fibrillation published in volume 70 of the Journal of the American College of Cardiology. In this article, Iwasawa and colleagues discuss the role of novel temperature controlled irrigated ablation catheter to attempt to obtain deeper transmural lesions in cardiac tissue, specifically they tested the utility of a diamond embedded tip for rapid cooling accompanying six surface thermocouples to better reflect tissue temperature.                                                 They demonstrated in this first in human series that a temperature controlled irrigated ablation could produce rapid, efficient and durable PV isolation. The importance of this particular article lies in the continued development of novel tools that can achieve pulmonary vein isolation either more safely or more quickly. This was highlighted in the article by Iwasawa et al when they demonstrated that the mean radiofrequency application duration was significantly less by almost a factor of three and those using the novel radiofrequency ablation catheter versus those with older models.                                                 They also noted that there was lower acute dormant pulmonary vein re-conduction rates and patients tend to have more frequent durable isolation when remapped after ablation. While the study group only consisted of 35 patients within the treatment group and 35 patients within the control group, the potential of these novel catheters to achieve aims of both shortening procedure duration as well as improving procedure and success need to be taken in consideration.                                                 The next article is by Dr. Gopinathannair entitled Atrial Tachycardia after Surgical Atrial Fibrillation Ablation Clinical Characteristics, Electrophysiological Mechanisms and Ablation Outcomes from a large multicenter study published in the August 2017 issue of JACC Clinical Electrophysiology. In this article, Dr. Gopinathannair reviews the outcomes of cardiac mapping and ablation targeted atrial tachycardias occurring after surgical atrial fibrillation ablation. They reviewed a large number of patients nearly 137 undergoing catheter ablation for symptomatic postsurgical atrial fibrillation ablation atrial tachyarrhythmias across three high volume institutions in the United States.                                                 They demonstrated that the vast majority had a left atrial origin though up to a third also had a right atrial origin further atrial tachyarrhythmias. The predominant circuits noted were cavotricuspid isthmus but also frequently perimitral roof and left or right pulmonary veins. In addition, most of the patients namely 93% had at least one pulmonary vein reconnection requiring re-isolation. The key point with the article however were the outcomes. They demonstrated that acute termination inducibility could be achieved in as many as 97% of right atrial and 93% of left atrial tachyarrhythmias in the setting of prior surgical ablation.                                                 Furthermore, 12 month followup demonstrated an 80% success rate. Traditionally, surgical atrial fibrillation ablation is seen as a complex procedure with the remapping of arrhythmias requiring a lot more complexity. However, these findings cross a large group of patients suggesting that we can have a high rate of success should propose to individuals that perhaps targeted ablation at these postsurgical atrial tachyarrhythmias should be amenable towards ablation especially at high volume complex ablation centers.                                                 Next will discuss the article by Pathik et al entitled Epicardial-Endocardial Breakthroughs through Stable Macroreentry: Evidence from ultra-high-resolution three-dimensional mapping published in Heart Rhythm in August 2017. In this article, the group of Pathik et al decided to review whether epicardial-endocardial breakthrough could be discerned during stable right atrial macroreentry using high density and high spatial resolution three-dimensional mapping. Twenty-six patients were studied and they noted that up to 14 patients had evidence of epicardial-endocardial breakthrough. Using systematic entrainment confirmation, stable atrial macroreentry with epicardial-endocardial breakthrough was consistently demonstrated.                                                 The principle of epicardial-endocardial breakthrough or dissociation is critically important during cardiac mapping. While widely accepted for ventricular mapping, the tradition because of lack of available tools and atrial mapping has suggested that endocardial only mapping should reveal the entire cardiac circuits. Advances in signal processing as well as cardiac mapping techniques and technologies has allowed for better discernment of potentially deeper manifestations of cardiac tissue involvement in cardiac arrhythmias. As been well recognized that there can be significant epicardial and endocardial dissociation in cases of persistent atrial fibrillation.                                                 The article by Pathik et al is important in that it highlights that such events can manifest themselves even in the setting of relatively organized or stable atrial macroreentry. Part of the reason this becomes so critical is that when we consider endocardial only remapping and rely on these signals alone, we may run into situations where we miss a significant chamber of atrial tissue namely the epicardium, thus the focus of this article and the consideration of it in the clinician's repertoire of cardiac mapping and ablation should lie in an understanding of the fact that the entire story of an electrical circuits may not be told by traditional endocardial mapping alone without consideration for epicardial-endocardial breakthrough.                                                 The next article we will focus on is by Dr. Chun et al regarding the impact of cryoballoon versus radiofrequency ablation for paroxysmal atrial fibrillation on healthcare utilization and costs and economic analysis. This was from the FIRE and ICE Trial published in the Journal of the American Heart Association this past month. In this study they sought to assess payer cost following cryoballoon or radiofrequency catheter ablation for paroxysmal atrial fibrillation. They demonstrated that there are cost savings of as much as $355,000 related to the use of cryoballoon over traditional radiofrequency catheter ablation. This reduction in resource use and payer costs was consistent across three different national healthcare systems.                                                 Furthermore, the reason for the reduced cost was primarily attributable to fewer repeat ablations and a reduction in cardiovascular rehospitalizations with cryoballoon ablation. In this era of cost reduction, it is important to consider the potential implications of use of novel technologies in terms of procedural costs. The ability to identify novel techniques that can actually both reduce costs and either achieve equal or improved outcomes needs to be strongly considered. While the three national healthcare systems reviewed here might not reflect all healthcare systems or all insurance needs, it still brings up an important economic consideration that all novel technology may not necessarily result in increased costs, and utilization must be considered both in the context of the particular system as well as the particular provider.                                                 Changing pace, we’ll move on with an atrial fibrillation to the role of anticoagulation. The first major article recently published is by Pollack et al regarding the use of Idarucizumab for dabigatran Reversal, the full cohort analysis published the New England Journal of Medicine. Idarucizumab is a monoclonal antibody fragments developed to reverse the anticoagulant effect with dabigatran and represents the first reversal agent available for reversal of any of the novel oral anticoagulant drugs. In this study which is both multicenter, prospective and open label, patients were enrolled to undergo treatment with this reversal agents.                                                 A total 503 patients were included and the median maximum percentage reversal dabigatran was 100% which was measured using the diluted thrombin time or the ecarin clotting time. In those with active bleeding, the median time to cessation of bleeding was around 2.5 hours. Furthermore, in a surgical cohorts who underwent reversal in order to accommodate them going to surgery, the time to initiation of an intended procedures was 1.6 hours with periprocedural hemostasis assessed as normal in 93%, mildly abnormal in 5% and moderately abnormal in 1.5%. Thrombotic events occurred in about 6.3% of patients undergoing reversal because of active bleeding and then 7.4% undergoing reversal for surgical accommodation.                                                 Mortality rates were around 18% to 19%. Thus it was demonstrated that in emergency situations Idarucizumab can rapidly, durably and safely reverse the anticoagulant effect of dabigatran. However, it is important to note that there was a signal for thrombotic events and consideration of the risk of rapid reversal of anticoagulation regardless of the type of anticoagulation in combination with the actual need for reversal should be considered in the patient context.                                                 The next article we will review is by Jackevicius et al entitled Early Non-persistence with Dabigatran and Rivaroxaban in Patients with Atrial Fibrillation, published in Heart this past month. In this article, the group reviewed how patients manage being on their novel oral anticoagulants over the course of time after initial diagnosis and prescription. One of the concerns regarding novel oral anticoagulants is given the fact that there is no actual tracking or no actual measurements needed to ensure continued adherence to the drug, whether or not there will be higher rates of nonpersistence with use of these novel oral anticoagulants.                                                 Amongst 15,857 dabigatran users and 10,119 rivaroxaban users, they noted that at six months about a third of patients were nonpersistent with either drug. In those patients who were nonpersistent with use of the drug, the combined endpoint of stroke, TIA and death was significantly higher with hazard ratios of 1.76 in the dabigatran cohort and 1.89 in the rivaroxaban cohort. Furthermore, the risk of stroke or TIA was markedly higher in nonpersistent patients with about a hazard ratio of 3.75 in dabigatran nonpersistence and 6.25 in rivaroxaban nonpersistence.                                                 Given these relatively high rates of nonpersistence in clinical practice and the negative outcomes associated with nonpersistence, this highlights the importance of continued validation of the need for persistence with use of oral anticoagulation in patients prescribed these perceived to be at high risk of stroke associate with atrial fibrillation. In an era of improving drug use or improving drugs that can be used without the need for blood testing, it must also be considered that these drugs may be more easily stopped on the patient's own discretion without any knowledge from a provider as there is no active blood test associated. Thus this further highlights the importance of continued discussion between patients and physicians over the course of therapy and care regarding the need for continuation.                                                 Changing paces. We review the article by Godier et al entitled Predictors of Pre-procedural Concentrations of Direct Oral Anticoagulants a prospective multicenter study published at the European Heart Journal. We all know that one of the major issue with a direct oral anticoagulants is that these patients frequently undergo elective invasive procedures and in this setting the management can be very challenging specifically as it relates to when the direct oral anticoagulants should and can be safely stopped.                                                 In clinical practice, there is wide variability in the timing by which providers inform patients to stop these new oral anticoagulants prior to invasive procedure. In this prospective multicenter study, 422 patients were evaluated with preprocedural DOAC concentrations and routine hemostasis assays performed to determine those patients who achieved a minimal preprocedural concentration based on the timing of their discontinuation of the drug. They ranged the duration of discontinuation of the oral anticoagulant from 1 to 218 hours. They noted after a 49 to 72 hour discontinuation period, 95% of the concentration of the direct oral anticoagulants in patients had levels that were significantly low suggesting safety and proceeding with any sort of invasive procedure.                                                 Thus a 72 hour discontinuation period predicted sufficiently low concentrations of DOACs with 91% specificity. In multivariable analyses, duration of the DOAC discontinuation with creatinine clearances and antiarrhythmics were independent predictors of a minimal preprocedural DOAC concentration, namely better renal function, longer duration of DOAC discontinuation and interestingly the use of antiarrhythmic drugs were all associated with lower DOAC concentrations. The conclusion from this article was a last DOAC intake of three days before a procedure resulted in a minimal preprocedural anticoagulant effect for almost all patients considered.                                                 The exception would be in moderate renal impairment especially in dabigatran treated patients and antiarrhythmics in anti-Xa-treated patients could result in the need for longer DOAC interruption. Thus, the key things here to note are that antiarrhythmics can result in the need for longer DOAC interruption to achieve minimal blood concentrations and that similarly moderate renal impairment especially in dabigatran treated patients may result in the same. Another outcome other studies suggested a lack of association between routine assays such as routine hemostasis assays and DOAC concentrations suggesting that in situations where testing is believed to be needed routine assays should not replace DOAC concentration measurement in decision-making regarding whether or not the DOAC has sufficiently gone down in concentration to safely proceed.                                                 Along these lines, the final article we will review within the realm of anticoagulation is by Brendel et al entitled the Anticoagulant Effect of Heparin during Radiofrequency Ablation in Patients Taking Apixaban or Rivaroxaban published in the Journal of Interventional Cardiac Electrophysiology this past month. One concern regarding the use of the direct oral anticoagulants is the fact that during procedures where heparin is needed, knowledge of how much heparin to give is unclear. This is both in the setting of understanding what the synergistic effect of the simultaneous and continued use of apixaban or rivaroxaban or other direct oral anticoagulants in combination with heparin might be and also what the effect on actual activated coagulation time might be.                                                 As it is felt that be ACT may not necessarily reflect the true anticoagulant activity of drugs. Thus in a prospective study, Brendel et al studied about 90 patients with atrial fibrillation undergoing radiofrequency ablation procedures. During radiofrequency ablation, unfractionated heparin was given to maintain ACT of 250 to 300 ms with blood samples taken before and up 360 minutes after heparin administration. They demonstrated that heparin displayed a lower anti-Xa activity in rivaroxaban treated patients compared to apixaban treated patients.                                                 In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin combinations than in rivaroxaban/heparin combinations. While there was clear differences in the level of anticoagulant effect, depending on which DOAC was combined with heparin, they had no clinical impact in terms of bleeding or thromboembolic complications from the procedure. This article is significant in that it highlights that there are clear and different biochemical responses based on which DOAC is used in combination with heparin during radiofrequency ablation.                                                 While in the small study, there was no clear effect on clinical impact, precautions should still be considered when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement especially considering the variability that might occur between DOACs themselves and not just between DOACs and warfarin.                                                 Changing paces to risk stratification and management within atrial fibrillation. We’ll review the article by Labombarda et al entitled Increasing Prevalence of Atrial Fibrillation and Permanent Atrial Arrhythmias in Congenital Heart Disease published in this past month's issue of the Journal the American College of Cardiology. In this article, they sought to assess the types and patterns of atrial arrhythmias, associate factors and age-related trends in a multicenter cohort of patients with adult congenital heart disease. What they demonstrated is that by far the most common presenting arrhythmia was intraatrial reentrant tachycardia in almost two-thirds of patients with the remaining including atrial fibrillation in up to 30% of patients and focal atrial tachycardias in up to 10% of patients.                                                 The association of intraatrial reentrant tachycardia with congenital heart disease was stronger with higher complexities of congenital heart disease. With those with more complex defects having a higher frequency of IART than those with simple effects. Furthermore, as is commonly seen in the general population, the frequency of atrial fibrillation increased with age to eventually suppress IART as the most common arrhythmia in those greater than equal to 50 years of age. The predominant arrhythmia pattern was paroxysmal in almost two-thirds of patients though almost 30% were persistent.                                                 Furthermore, the frequency of permanent atrial arrhythmias increased with age. While it is commonly seen that patients with congenital heart disease were living longer and as a result it is expected that the frequency of arrhythmias in this population will likely increase. The interesting outcome from the study is the high frequency of intraatrial reentrant tachycardia as the presenting atrial arrhythmia in patients with congenital heart disease and also with the predominantly paroxysmal pattern. The finding also that atrial fibrillation increases in prevalence highlights the importance of closely monitoring these patients in order to assess for anticoagulation needs and options for treatment.                                                 Changing gears to cellular electrophysiology. We focus on an article by Qiao et al entitled transient Notch activation induces long-term gene expression changes leading to sick sinus syndrome in mice published in this past month's issue of Circulation Research. Notch signaling programs cardiac conduction during development and in the adult ventricle. It is noted that injury can induce notch reactivation resulting in global transcriptional and epigenetic changes. Thus, the group sought to determine whether notch reactivation may alter atrial ion channel gene expression arrhythmia inducibility.                                                 They demonstrated that notch signaling regulates transcription factor in ion channel gene expression in adult atrial myocardium. With reactivation inducing electrical changes resulting in sinus bradycardia, sinus pauses and a susceptibility atrial arrhythmias, altogether contributing to a phenotype resembling sick sinus syndrome. The importance of these findings lies in the mechanism underlying sick sinus syndrome.                                                 While we search for genetic clues for why patients might develop atrial fibrillation or sick sinus syndrome or sinus bradycardia as they age, the importance of activation of typically quiet signaling patterns in the adult myocardium and their role in arrhythmogenesis is important because it might highlight novel targets for treatment. Understanding how the arrhythmogenic substrate develops and the mechanisms underlying it, may allow for a better understanding of why in certain patients certain drugs may be effective or not or certain invasive therapies may be effective or not.                                                 Next with the realm of electrocardiography, we’ll review the article by Christophersen et al entitled 15 Genetic Loci Associated with Electrocardiographic P-wave published in Circulation Genetics this past month. Similar to the previous article by Dr. Qiao et al, the importance of the article by Christophersen et al lies in the identification of a number of genetic underpinnings for what forms the final electrocardiographic P-wave that is seen.                                                 Six novel genetic loci associated with P-wave duration and six novel loci associated with P-wave terminal force were identified by the group. Both in the case of the transient Notch activation findings as well as in the findings related to a specific genetic loci associated with electrocardiographic P-wave abnormalities might highlight potential genetic targets either with existing drugs not traditionally used for atrial electrophysiology or potentially future drug targets.                                                 Changing gears yet again, we’ll move on to their own sudden death cardiac arrest and specifically to an article published by Fallavollita et al entitled the denervated myocardium is preferentially associate with sudden cardiac arrest in ischemic cardiomyopathy a pilot competing risks analysis of cost specific mortality. Previous studies identify multiple factors associated with total cardiac mortality but we all recognize the ejection fraction has limited value. Thus within this article published in Circulation: Cardiovascular Imaging, the group decided to do a competing risks analysis the National Institutes of Health sponsored prediction of arrhythmic events with positron emission tomography trial.                                                 They demonstrated that sudden cardiac arrest was correlated with greater volumes of denervate myocardium based on defects on positron emission tomography using a norepinephrine analog carbon 11 hydroxy ephedrine. However, they also demonstrated that other factors such as lack of angiotensin inhibition therapy, elevated BNP and large left particular end-diastolic volume were further associated with sudden cardiac arrest.                                                 The importance of potential modifying factors to better attribute cardiac arrest risk and thus the need for defibrillator or other therapies in patients with myopathy needs to continue to be highlighted especially in light of recently published Danish and other studies suggesting that the mortality benefit conferred by ICD is an ischemic and nonischemic populations may not be equivalent in newer studies. The fact that further risk stratification opportunities can exist underlying the pathophysiologic basis for why these patients develop ventricular arrhythmias is critical. While recognized for a few decades now that myocardial denervation may be associated with sudden cardiac arrest risk, this study highlights the continued need for further study to help further clarify these populations.                                                 Moving onto the realm of genetic channelopathies, we review the article by Anderson et al entitled Lidocaine Attenuation Testing: An in vivo Investigation of Putative LQT3-Associated Variants in the SCN5A-encoded sodium channel published in this past month's issue of Heart Rhythm. Long QT syndrome type 3 represents one of the more difficult types of long QT syndrome to adequately diagnose both by genetic testing as well as through traditional means. Approximate 2% of healthy individuals can have rare variance of uncertain significance in the SCN5A channel and thus distinguishing true LQT3 causative mutations for background genetic noise can be quite difficult in this population.                                                 Anderson et al decided to assess the utility of lidocaine attenuation testing in evaluating patients with possible LQT3. They gave a loading dose of 1 mg per kg of intravenous lidocaine followed by continuous infusions of 50 micrograms for 20 minutes. If the corrected QT interval shortened by at least 30 ms, the LAT was defined as positive. They demonstrated that use of this test can help distinguish true LQT3 causative mutations from otherwise noncontributory variance of uncertain significance. Thus in this era of increasing genetic testing where one might identify a variant of uncertain significance in either a family member affected with sudden cardiac arrest or in a patient being evaluated for any sort of uncertain significant variant, the use of lidocaine testing in those variance as they apply to LQT type 3 may offer significant clinical use.                                                 Next we will review the article by Ishibashi et al published in this past month's edition of Heart entitled Arrhythmia Risk and Beta Blocker Therapy in Pregnant Woman with Long QT Syndrome. One of the biggest concerns of patients with long QT syndrome especially woman is pregnancy. The fact is because of the different hormonal states, it is possible that pregnancy may alter arrhythmic risk and the safety of beta blocker therapy given both the potential fetal effects as well as the continued efficacy at the level those seen previously.                                                 Thus Ishibashi et al reviewed 136 pregnancies across 76 long QT pregnant patients. They retrospectively analyzed clinical and electrophysiological characteristics in pregnancy outcomes in both the presence and absence of beta blocker therapy. All of the beta blocker group had prior events while the majority of the nonbeta blocker group had not been diagnosed with pregnancy. Pregnancy was noted to increase heart rate in those not treated with beta blockers, but interestingly, between the two groups there was no significant difference over the course of pregnancy in QT intervals.                                                 In the beta blocker group, only two events occurred and these were relegated to the postpartum period. However, 12 events occurred in the nonbeta blocker group either during pregnancy and half or in the postpartum period and the remaining half. There was no difference in this frequency of spontaneous abortion between the two groups, and furthermore, fetal growth rates and proportion of infants with congenital malformation were similar between the two groups. However, premature delivery and low birth weight infants were more common in those taking beta blockers.                                                 Given the high risk of events and the relative safety of beta blocker therapy in this population of patients with long QT who become pregnant, it was felt that the use of early diagnosis and beta blocker therapy could be critical both the during pregnancy and during the postpartum period. It was also felt the beta blocker therapy may be tolerated for babies in long QT pregnant patients. This highlights that the continued use of beta blockers throughout the pregnancy and consideration of the introduction of beta blockers in those not already on them during pregnancy may be an important consideration.                                                 Finally within the realm of genetic channelopathies, we focus on the article by Roberts et al entitled Loss of Function in KCNE2 Variants: True Monogenic Culprits of Long QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation published in this past month's issue of Circulation: Arrhythmia Electrophysiology. As we identify more and more genes the baby is associated with long QT syndrome, the understanding of the clinical phenotype associated with that syndrome requires better study. In this particular study, Roberts et al reviewed the role of long QT syndrome type 6 stemming from mutations in the KCNE2 encoded voltage gated channel beta subunits.                                                 They reviewed mutations identified during arrhythmia evaluation from either inherited arrhythmia clinics or the Rochester long QT syndrome registry. They demonstrated that the high allelic frequencies of LQT6 mutations in the Exome aggregation consortium database and the absence of previous documentation of genotype phenotype segregation suggest many KCNE2 variants and potentially all were actually erroneously designated as LQT as causative mutations. Instead, it was felt the KCNE2 variants may actually confer proarrhythmic susceptibility when provoked by additional environmental and/or acquired or genetic factors.                                                 What they are saying is that identifying the KCNE2 variants as the principal culprits may be over calling the role of the KCNE2 variants and instead it might be a combination of effects such as two hit affect the requires further provocation by either outside or additional genetic factors. Furthermore, complex genetic studies were likely needed to better understand how variants and genes that may not have been previously designated as disease causing play a role in the actual disease process, whether as potentiating other factors that might exist that might also otherwise be relatively benign or as unique singular hits that might by themselves result in the clinical phenotype.                                                 Next moving onto the realm of ventricular arrhythmias, we first focus on an article published in this past month's issue of the American Journal of Physiology, Heart and Circulatory Physiology by Howard Quijano et al entitled Spinal Cord Stimulation Reduces Ventricular Arrhythmias during Acute Ischemia by Attenuation of Regional Myocardial Excitability. In this article, they demonstrated in a porcine model ventricular ischemia that spinal cord stimulation decrease sympathetic nerve activation regionally in ischemic myocardium while having no effect on normal myocardium. They demonstrated that the antiarrhythmic effects conferred by spinal cord stimulation were likely secondary to attenuation of some sympathoexcitation locally in ischemic myocardium rather than changes in the global myocardial electrophysiology.                                                 This is important because it highlights the mechanisms by which spinal cord stimulation may confer in antiarrhythmic benefits in both animal and human models. As we search for novel interventions that can be used for the treatment of ventricular arrhythmias, understanding the underlying pathophysiologic mechanisms by which they work is critical. The understanding that the use of spinal cord stimulation is primarily conferred in a regional way primarily in terms of its effect on an ischemic myocardium, further study is also needed in terms of how the effect is seen in nonischemic myopathies where there may be more patchy scar in the same role of denervation, nerve sprouting and hyper innervation may play different roles.                                                 In the next article we choose to focus on is by Berte et al entitled a New Cryo-energy for Ventricular Tachycardia Ablation a Proof of Concept Study published in this past month's edition of Europace. One of the key problems in ventricular tachycardia ablation is the lack of transmural lesion formation. This is an important determinant of arrhythmia recurrence. Thus the group decided to do a proof of concept study to evaluate the safety and efficacy of a new and more powerful cryoablation system for ventricular ablation. They demonstrated that a novel cryoablation system to create large transmural ventricular lesions, whether it delivered by endocardial or epicardial approach. It was felt that this technology can hold potential for both surgical and catheter-based VT ablation in humans.                                                 While primarily studied in sheep models, it nevertheless highlights the importance of novel therapies that might better achieve through and through lesions. There are many different novel products being developed for the hope of achieving transmural lesions partly to target the myocardial circuits and partly to ensure achievement of through and through lesions without leaving residual potential substrate, because of only partial thickness lesions. These include things like needle ablation catheters, the safety of which still has to be fully evaluated, bipolar ablation or the use of technology such as novel cryo-energy approaches. Comparative efficacy of these different approaches however will be critical to determining which one is safest and best in any given clinical situation.                                                 Next we’ll review the article by Venlet et al published this past month's issue of Circulation Arrhythmia and Electrophysiology entitled Unipolar Endocardial Voltage Mapping in the Right Ventricle: Optimal Cutoff Values Correcting for Computed Tomography-derived Epicardial Fat Thickness and their clinical value for substrate delineation. The work by [inaudible 00:53:37] and others highlighted the importance of using unipolar and bipolar voltage cutoffs and helping delineate areas of both endocardial as well as potentially more distal such as epicardial scar during endocardial mapping. It is felt the low endocardial unipolar voltage during bipolar voltage mapping endocardially may indicate epicardial scar.                                                 However, the primary issues, the additional presence of epicardial fat both in the right ventricle and left ventricle and how this epicardial fat may effect normal unipolar voltage cutoffs. Thus, Venlet et al decided to review using computed tomography data the effective epicardial fat on unipolar voltage cutoffs. They demonstrated that endocardial unipolar voltage cutoff of 3.9 millivolts was more accurate than previously reported cutoff values for right ventricular epicardial scar during endocardial mapping.                                                 It was further demonstrated that while epicardial abnormal electrograms may be associated with transmural scar when associated with low endocardial bipolar voltage, the additional use of endocardial unipolar voltage and normal bipolar voltage sites can improve the diagnostic accuracy resulting in identification of all epicardial abnormal electrograms at sites with less than 1 mm of fat. Thus, the unipolar voltage not only assisted in evaluating whether epicardial scar was present, but also in further clarifying epicardial abnormal electrograms in terms of whether or not they truly represented potential transmural scar.                                                 Finally, within the realm of electrogram mapping of ventricular arrhythmias, we focus on the article by Magtibay et al entitled Physiological Assessment of Ventricular Myocardial Voltage using Omnipolar Electrograms published in the Journal of the American Heart Association this past month. Bipolar electrograms are traditionally used to characterize myocardial health. However, dependence on these electrograms may reduce the reliability of voltage assessment along different planes of arrhythmic myocardial substrates.                                                 Thus, newer catheters rely on evolving tools that might allow for different approaches to bipolar mapping. Using omnipolar electrograms, Magtibay et al studied in healthy rabbits, pigs and diseased humans under paced conditions the role of two bipolar electrode orientations both horizontal and vertical. Voltage maps were created for both bipoles and omnipoles, and they noted that electric orientation affected the bipolar voltage map with an average absolute difference between horizontal and vertical of up to 0.25 millivolts in humans. Thus, they demonstrated omnipoles can provide physiologically relevant and consistent voltages along the maximal bipolar direction and provide an advantage over traditionally obtained bipolar electrograms.                                                 When we consider the use of evolving techniques to get an understanding of myocardial health whether for the purpose of cardiac mapping and ablation or even for the purpose of other intervention such as cardiac biopsy, understanding what the voltage abnormalities perceived actually are is critical to understanding what substrate is actually being targeted. However, given directionality issues in terms of assessment of voltage as well as relative orientation of the catheter in understanding the relevance of received voltage, use of novel signal processing and electro designs are important to consider in the light of their effects on substrate mapping compared to traditional techniques.                                                 Changing gears yet again, but nevertheless related to cardiac mapping and ventricular arrhythmias, we focus on article by Yalagudri et al published in this past month's issue of the Journal of Cardiovascular Electrophysiology entitled A Tailored Approach for Management of Ventricular Tachycardia in Cardiac Sarcoidosis. While in a small number of patients, nearly 14 patients, they attempt to develop a methodology for approaching patients with cardiac sarcoidosis for management of their ventricular arrhythmias. Patients with either cardiac myocarditis or cardiac sarcoidosis represent a particularly difficult cohort to treat.                                                 Prior work by Dr. Roderick Tung and others has demonstrated the high-frequency of perceived inflammatory abnormalities based on cardiac FDG PET scanning amongst patients with ventricular arrhythmias. Whether this reflects cardiac sarcoidosis or other hypermetabolic activity is unclear. However, how to take into account the FDG PET abnormalities when deciding whether or not to take a patient for ablation or how to best treat them in light of their primary disease process is critical.                                                 In this study, the group tried to tailor therapy for ventricular tachycardia and cardiac sarcoidosis according to the phase of disease results. Namely based on the degree of inflammation noted on the FDG PET scan. They noted that via their named clinical protocol, that this tailored therapy could result in good clinical outcome and avoid unnecessary immunosuppression in some patients. Whether or not the use of this tailored therapy approach may apply in larger populations remains to be seen.                                                 Finally within the realm of other EP concepts that might apply broadly across the electrophysiology landscape, we focus on two articles. The first is by Kudryashova et al entitled Virtual Cardiac Monolayers for Electrical Wave Propagation in Nature Scientific Reports this past month. It is the complex structure of cardiac tissue that is considered to be one the main determinants of whether a substrate becomes arrhythmogenic or not. Multiple mathematical and computational models have been developed in order to recapitulate this complex cardiac structure. However, there been varying degrees of limitations in these approaches.                                                 Using a joint in silico-in vitro approach, the group carefully characterized the morphology of cardiac tissue and cultures of neonatal rat ventricular cells and then proposed mathematical models to result in tissue morphology that could be recapitulated for virtual studies of cardiac electrophysiology mainly in order to study wave propagation. They demonstrated in their virtual cardiac monolayers, that the simulated waves had the same anisotropy ratios and wave form complexity as those in in vitro experimental models.                                                 Thus, they demonstrated that they could reproduce both the morphological and physiological properties of cardiac tissue in a virtual landscape. These findings are critical to improving the ability to better study the effects of different antiarrhythmic drugs or interventional techniques on overall cardiac electrophysiology. The difficulty in existing techniques using traditional in vitro cultures is the fact that they’re costly and requires sacrifice of animals that adds to the additional cost of routine studies. The ability to recapitulate actual hearts within a virtual landscape to mimic the cardiac electrophysiology and then study it in a more controlled setting that can be reproducible based on the availability of appropriate computing power is important in terms of future studies within the realm of our field.                                                 The final article we will review is by Das and Dutta published in Physical Review E this past month entitled Controlling Three-Dimensional Vortices using Multiple and Moving External Fields. One of the key studies over the course of the last several years has been that of the role of the spiral and scroll waves in not just atrial fibrillation but ventricular fibrillation and other arrhythmias. It is well recognized that the spiral or scroll waves depending on whether one thinks in a two dimensional or three dimensional substrate may have significant contribution to arrhythmogenesis. Whether targeting the spiral or scroll waves actually eliminates arrhythmias remains to be fully elucidated. However, it also remains to be elucidated exactly how one should control the spiral or scroll waves.                                                 The review by Das and Dutta demonstrated that in fact the spiral or scroll waves could actually be physically moved around and controlled using moving external electric fields and thermal gradients. They show that the scroll rings can be made to trace cyclic trajectories on a rotating electric field or that application of thermal gradients in addition to electric field could deflect the motion and change the nature of a trajectory of a spiral or scroll wave. These findings are important in that they might represent non-ablative techniques that can eventually be used to control spiral or scroll waves in cardiac media, and thus result in either their alteration or termination without the need for additional cardiac injury.                                                 One the biggest problems with additional cardiac ablation in cases such as atrial fibrillation is the fact that they often lead to additional regions of scarring that might lead towards further organized atrial arrhythmias. However, the ability to potentially terminate critical sites responsible for arrhythmogenesis in real time without the need for ablation may represent novel interventions or devices in the future.                                                 I appreciate everyone's attention to these key and hard-hitting articles that we have just focus on from this past month of cardiac electrophysiology across the literature. Thanks for listening. Now back to Paul. Dr. Paul Wang :                 Thanks Suraj. You did a terrific job surveying all journals for the latest articles on topics of interest in our field. There is not an easier way to stay in touch with the latest advances. These summaries and a list of all major articles in our field each month could be downloaded from the Circulation: Arrhythmia and Electrophysiology website. We hope that you’ll find the journal to be the go to place for everyone interested in the field. See you next month.

Dr. Wang:            Welcome to the monthly podcast On The Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field.                                 This month's issue of Circulation: Arrhythmia and Electrophysiology has a number of fascinating and important articles. Let's start with the first article by Philip Halbfass and Associates, which describes the use of esophageal endoscopy in patients undergoing atrial fibrillation ablation. Of 1,802 patients undergoing afib ablation, 832 underwent post-procedural esophageal endoscopy. All patients were ablated using a single tip re-circular ablation catheter. Category one lesions described as erythema erosion were seen in 98 out of these 295 patients, while in 52 out of the 295 patients, ulceration was seen. In three of the 832 patients, esophageal perforation occurred, and in two of the 832 patients, atrial-esophageal fistula occurred.                                 Esophageal perforation only occurred in patients with category two lesions with an absolute risk of 9.6%. The authors concluded that post-ablation esophageal endoscopy is able to identify patients with high-risk lesions. One out of 10 patients with post-ablation esophageal ulcers progressed to perforation, while no patients without esophageal ulcers showed evidence of perforating complications.                                 In the next article by Christian Sohns and Associates describes the relationship between atrial fibrosis identified with magnetic resonance imaging and atrial rotor activity identified by noninvasive electrophysiological mapping. Ten patients underwent pulmonary vein isolation for persistent atrial fibrillation. Late gadolinium enhancement using magnetic resonance imaging, which projected onto the anatomy used for noninvasive electrophysiologic mapping.                                 The noninvasive electrophysiologic mapping identified 410 rotors evenly distributed between the left atrium and the right atrium. This study found that there was no statistically significant association between the presence of late gadolinium enhancement and the presence of rotors.                                 In the next article written by Jereon Venlet examines the endocardial unipolar voltage that best identifies abnormal epicardial electrograms. Thirty-three patients underwent endocardial epicardial right ventricular electro-anatomical mapping in ablation of right ventricular scar-related ventricular tachycardia. Eighty-six percent of abnormal epicardial electrograms had corresponding endocardial sites with bipolar electrogram less than 1.5 millivolts.                                 The remaining abnormal epicardial electrograms could be identified by endocardial unipolar voltages of less than 3.7 millivolts. The authors concluded that this use of endocardial unipolar voltage cut off at normal bipolar voltage sites improves the identification of all abnormal epicardial electrograms where there is less than 1 millimeter of fat.                                 The next article by Alan Bulava and Associates examines the outcomes of hybrid epicardial and endocardial radial frequency ablation, a persistent atrial fibrillation. Seventy patients underwent the epicardial thoracoscopic procedure followed by endocardial mapping ablation two to three months later. At the time of catheter ablation, 76% of patients were in sinus rhythm. All four pulmonary veins were found to be isolated in 69% of the patients and the left atrial posterior wall was isolated in 23% of the patients.                                 In the 12 months after the catheter ablation, 77% were arrhythmia-free, off antirrhythmic drugs. The majority of arrhythmia occurrences occur during the first 12 months following catheter ablation. Using previously ineffective antiarrythmics drugs and re-ablation procedures, arrhythmia-free survival increased to 97% during a mean followup of 936 days. Left atrial volume greater than 165 milliliters, the absence of sinus rhythm before catheter ablation and induce-ability of any sustained tachyarrhythmia at the end of catheter ablation predicted atrial fibrillation recurrence.                                 The authors concluded that the majority of patients after epicardial ablation required endocardial catheter ablation to complete the linear ablation or pulmonary vein isolation lesion sets. In the next article, Jason Roberts and Associates studied the clinical phenotype of Type 6 Long QT Syndrome, stemming from mutations in the KCNE2 encoded voltage gated channel beta subunit.                                 The authors examined individuals reported pathogenic KCNE2 mutations collected from inherited arrhythmia clinics in the Rochester LQTS registry as well as previously reported LQT6 cases identified through a med-line database search. Of 44 probands studied, 16 probands had resting QTC intervals and only developed QT prolongation and malignant arrhythmias following exposure to QT prolonging stressors. Ten had other Long QT pathogenic mutations and 10 did not have a Long QT phenotype, with the remaining eight subjects having a Long QT phenotype, but with evidence suggesting that the KCNE2 variant was not the underlying culprit.                                 The authors noted that the collective frequency of KCNE2 variance implicated in Long QT6 syndrome in the exome aggregation consortium database was 1.4%, in comparison with the 0.0005% estimated clinical prevalence of LQT6 syndrome. Thus, the authors concluded that based on clinical phenotype, the high allelic frequencies of LQT6 mutations in the exome consortium database, in absence of prior documentation of genotype phenotype segregation, many KCNE2 variants, and perhaps all have been erroneously designated as long QT syndrome causative mutations.                                 Instead, KCNE2 variants may confer pro-arrhythmic susceptibility when provoked by additional environmental acquired or genetic factors. In the next article, Alexander Quinn and Associates examine how mechanically-induced ectopy may cause ventricular fibrillation, the mechanism of commotio cordis. It is known that the block of stretched sensitive ATP inactivated potassium channels limits ventricular fibrillation occurrence in a porcine model of commotio cordis.                                 In isolated rabbit heart preparations using optical voltage mapping combined with pharmacological block of potassium ATP or stretch activated cation nonselective channels, the authors showed that the mechanical stimulation reliably triggers premature ventricular excitation at the contact site with induce-ability predicted by local tissue indentation. Mechanically-induced premature ventricular excitation induction is decreased by stretch activated cation nonselective channel block.                                 The authors also found that mechanically-induced premature ventricular excitation resulted in ventricular fibrillation only if the mechanical stimulation site overlaps the re-polarization wave edge in hearts where T-waves involve a well-defined re-polarization edge traversing the epicardium. This defines a narrow subject-specific vulnerable window for commotio cordis-induced ventricular fibrillation in both time and space.                                 In the next article Matthias Seidl and Associates examine the gene expression required for development of atrial fibrillation in a transgenic mouse model. Recent studies showed that atrial fibrillation susceptibility is associated with down regularization of target genes of the CREB/CREM family of transcription factors. CREB/CREM refers to cyclic and P-response element binding protein modulator.                                 Short CREM repressor isoforms like CREM-IbΔC-X bind to cyclical A&P responsive elements preventing transcriptional activation. Messenger RNA for CREM-IbΔC-X is up-regulated in atrial biopsies from patients with paroxysmal or chronic atrial fibrillation. The authors examined transgenic mice expressing CREM-IbΔC-X, which spontaneously developed atrial fibrillation proceeding to permanent fibrillation with age.                                 The authors found that the most prominent alterations of the gene program linked to CREM-induced atria modeling were identified in expression of genes related to structure, metabolism, contractility and electrical activity regulation. In the next article by Takumi Yamada and Associates electrophysiologic characteristics of the idiopathic ventricular arrhythmias originating from the parietal band, one of the muscle bands of the right ventricle, were examined.                                  Of 294 consecutive patients with right ventricular origins, 14 patients had ventricular arrhythmia origins in the parietal band. All patients have left bundle block pattern with 12 inferior and two superior axis. All patients had the notch in the middle of the curess in all cases. Seven patients had precordial transition before lead V3 and four patients had a slow curess onset.                                 Far field ventricular electrogram with an early activation was always recorded in His bundle region regardless of the location of the ventricular arrhythmia origin. During the catheter ablation, a mean number of 10.4 radio frequency of applications with a mean duration of 1,099 seconds were delivered. Catheter ablation was successful in 10 patients and ventricular arrhythmias recurred in four with a mean followup of 41 months.                                 In the Advances in Arrhythmia and Electrophysiology section, the Buza and Associates have reviewed cancer treatment-induced arrhythmias. The authors describe ECD advances in arrhythmias associated with individual cancer chemotherapeutic agents. Now here with a review of the highlights from the articles from journals throughout the world in the past month, is Dr. Suraj Kapa. Dr. Kapa:              Hello. Today we're going to be going over several hard hitting articles we have identified that seem to stand out in the electrophysiological literature from the month of July 2017. The first area we will be delving into is that of atrial fibrillation. Specifically related to cardiac mapping and ablation. The first article in this area that we've chosen was published by Samuel et al. in the Journal of Cardiovascular Electrophysiology entitled Catheter Ablation for the Treatment of Atrial Fibrillation Is Associated with a Reduction in Healthcare Resource Utilization.                                 Samuel et al. reviewed data from a large population base cohort in Quebec, Canada including over 1,500 patients undergoing cardiac ablation for atrial fibrillation. They demonstrated that healthcare resource utilization including hospitalizations, emergency room visits and cardioversions were significantly reduced both 12 months as well as 24 months after the next ablation. These findings seem to suggest that catheter ablation has a sustained overall impact on resource utilization amongst patients with atrial fibrillation.                                 While the study was not randomized and was a retrospective evaluation of outcomes, these findings are provocative. Certainly as we wait for the results of the Cabana trial in about one year we hope to see whether or not cardiac ablation carries the weight of potential beneficial impacts both in terms of long-term care as well as long-term outcomes. Of course being a retrospective evaluation, one question that lies with regards to these findings is whether or not the reduction in resource utilization might be a byproduct of improved ambulatory care of these patients or whether it's a byproduct of patients understanding their disease process better, and thus perhaps not seeking emergency room care or hospitalization as frequently.                                 The next publication we'll focus on was published by Anselmino et al. in The International Journal of Cardiology entitled Conduction Recovery Following Catheter Ablation in Patients with Recurrent Atrial Fibrillation and Heart Failure. This publication synergizes with several other publications that have come out in the month of July. Focusing on the publication by Anselmino et al., they reviewed retrospectively patients undergoing redo atrial fibrillation ablation in the setting of underlying heart failure.                                 What they demonstrated was that nearly a third of patients had no pulmonary vein reconnection, but tended to have more persistent forms of atrial fibrillation suggesting more extensive atrial substraights. This study is complimentary to a publication by [inaudible 00:15:23] et al., published in JACC EP. this past month where they evaluated the longterm outcomes of patients who, when presenting for redo atrial fibrillation ablation had persistent pulmonary vein isolation.                                 In that article, they found that nearly 17% of patients presenting for redo ablation had persistent pulmonary vein isolation. Moreover, these patients tended to perform significantly worse in terms of longterm outcomes than those who presented with PV reconnection, with about a 56% freedom from affiliate swipe after we do ablation in the setting of persistent pulmonary vein isolation as opposed to 76% when there was PV reconnection seen.                                 So the question becomes if we see this greater atrial substraight, should we automatically be doing more ablation? Of course as we all know, there have been many studies performed trying to tease out whether additional ablation in patients who might have more significant atrial substraight carries benefits. In this regard, Fink et al. in last month's edition of Circulation, Arrhythmia and Electrophysiology demonstrated that in fact as an index procedure of performing a stepwise concomitant café plus linear ablation on top of pulmonary vein isolation in persistent and long standing persistent atrial fibrillation patients did not necessarily confer an increased likelihood of longterm success over pulmonary vein isolation alone.                                 Thus, the jury continues to still be out as far as what the right strategy is in many of these patients. However, these studies highlight the importance of continued evaluation and understanding of how we can use information about atrial substraight to guide our ablation procedures more successfully. Changing gears, we'll move on the pathophysiology mechanisms of disease within atrial fibrillation.                                 The article we will choose to focus on here was published by Die et al. in The Journal of Cardiovascular Electrophysiology entitled The Effects of Extrinsic Cardiac Nerve Stimulation on Atrial Fibrillation Induce-ability: The Regulatory Role of the Spinal Cord. Over the course of the last several years many investigators have sought to show that modulation of the autonomic nervous system can successfully alter cardiac electrophysiology and provide antiarrythmic benefits.                                 However, when subject to prospective trials such as the recently published Defeat HF Trial, they have not necessarily found clear benefit. Thus, a critical question becomes how we translate our animal models into human treatment. The interesting results from Die et al. lie in the fact that they looked at the effects of spinal cord stimulation and spinal cord block in addition to concomitant stimulation of other centers such as the venous nerve, the stellate ganglion and ganglionated plexi.                                 They demonstrated that spinal cord stimulation enhanced the effects of venial nerve stimulation while attenuating the effects of stimulating the left stellate ganglion or ganglionated plexus. In turn, the combinations of these different levels of stimulation had different effects on affiliate swipe induce-ability, whether significantly increasing or decreasing the potential.                                 The reason this article is important is it highlights the extensive cross linking and synergy that exists within the autonomic nervous system and that attention paid to only a single center of autonomic innovation may not be sufficient for certain paradigms of care. This past month there were also two reviews summarizing the role of the autonomic nervous system and modulation of that nervous system and the treatment of arrhythmias.                                 The first was by Witt et al. and Europace. The other by Schwartz et al. in the International Journal of Cardiology. These articles help the reader understand the extensive crosslinking and cross communication that might occur, that might sometimes defeat our efforts to use a single element of the autonomic nervous system to modulate cardiac arrhythmias. Changing gears yet again, we'll move on to risk stratification and management for atrial fibrillation.                                 Perino et al. in last month's edition of The Journal of the American College of Cardiology published an article entitled Treating Specialty in Outcomes in Newly Diagnosed Atrial Fibrillation from the Treat AF Study. They present data based on a very large cohort of over 180,000 veterans regarding the effect of treating specialty on atrial fibrillation outcome. Interestingly they demonstrated that when a cardiologist was involved in the care of the patient, there was an overall decrease in stroke and mortality.                                 Albeit with a concomitant increase in hospitalization for AF. The stroke reduction seen was also seen to be secondary to better anticoagulation prescription within 90 days of diagnosis when those patients were seen by a cardiologist as compared with a general internist. This earlier prescription anticoagulation however did not mediate the mortality reduction. These data presented by a Perino et al. are provocative in this era of rising healthcare costs.                                 The question is, as atrial fibrillation rates rise, as the general population ages, how quickly and how aggressively we should engage specialty care early on in patient evaluation. The data by Perino et al. suggests that maybe this engagement should occur earlier. Part of the reasons for this might be improved understanding of current evidence regarding treatment of such patients or better systems of care that allow for providers to identify patients who might need alterations and care faster.                                 However, if anything this is hypothesis-generating. Why anticoagulation prescriptions are delayed when patients are not seen by a specialist or why there would be a difference in mortality are important factors to review further. In this past month Hernandez et al. in Stroke published an article discussing the large degree of geographic variation that exists with regards to appropriate anticoagulation prescription in patients with atrial fibrillation.                                 They demonstrated that there's extensive inhomogeneity across the United States in terms of how and in whom anticoagulation gets prescribed. Thus, how much of these outcomes are specialist-driven, geographically-driven or based on elements of access to care or other issues are going to be important features that have to be evaluated.                                 The next article in risk stratification was published by Mostofsky et al. in Heart, entitle Chocolate Intake and Risk of Clinically Apparent Atrial Fibrillation: The Danish Diet, Cancer and Heart Study. In this study they demonstrated in a population of over 55,000 patients that when accounting for as many variables as they could, higher chocolate intake, more than once per month, was associated with a decreased atrial fibrillation risk when compared with those consuming less chocolate than once per month.                                 Of course, they note that despite these attempts to account for multiple confounding variables, residuary confounders cannot be accounted for. The relevance of this article lies in the question of lifestyle choices patients are asked to make when thinking about how to either prevent themselves from having atrial fibrillation or trying to even treat their atrial fibrillation risk.                                 Chocolate has been shown to have multiple potential beneficial effects in multiple areas of cardiology, however, how to counsel patients with data like these becomes very difficult. The questions lies in how chocolate might mediate arrhythmia risk and how it might also modulate other potential risks such as weight gain or other factors.                                 Thus while important to consider this in light of patients often asking what they can and cannot have, it is important to further consider that we don't understand the full story. The other key element to understand is that really when they say that chocolate intake reduces risk of clinically apparent atrial fibrillation they are speaking about moderate chocolate intake and not necessarily having it for three meals a day.                                 Changing gears away from atrial fibrillation, we will next focus on the area of ICDs pacemakers and CRT. Aberi et al. in Nature's Scientific Reports published regarding inductively power wireless pacing via miniature pacemaker and remote stimulation control system. Their approach provides potential novel opportunities beyond currently available both lead-based and leadless pacemakers and improving battery and allowing for further miniaturization of such devices.                                 They noted by creating a very novel inductive power supply they're able to miniaturize the pacing components and also significantly reduce the power requirements. In fact, they suggested that they could create a leadless device that could be as small as being delivered out of the anterior ventricular vein. This is the first report of such an inductively powered miniaturized pacing system with low enough power consumption that may prove viable for ambulatory human use.                                 The desire to create improved pacing and fibrillation systems is further highlighted by an article published by [Kalu 00:25:41] et al. in JACC Clinical Electrophysiology this past month where they demonstrated initial results of percutaneous epicardially delivered partially insulated defibrillator lead. Work like these holds the potential to improve options for patients and in traditional vascular access is not desired, or an identifying new ways of delivering pacing therapy that exists outside the traditional lead base or even somewhat miniaturized leadless approaches.                                 We'll next focus on the area of sudden death and cardiac arrest. The first article we'll focus on was published by Stecker et al. in The Journal of The American Heart Association entitled Health Insurance Expansion and Incidence of Out of Hospital Cardiac Arrest: A Pilot Study in the US Metropolitan Community. This article looked at the results of The Affordable Care Act, mainly health insurance expansion, on the rate of out of hospital cardiac arrest in a large US metropolitan community of over 600,000 people.                                 They separately studied a middle aged population that might have been affected by healthcare expansion versus an older population, above 65, who would have had relatively stable insurance plans having been covered by Medicare both prior to and after this change in healthcare plans. They demonstrated that there was a significant decrease in overall out of hospital cardiac arrests amongst middle age people without any significant change amongst the more elderly Medicare population in the same time period.                                 The time period studied was relatively short, nearly less than a decade. Of course, whether there were other events that might have occurred to alter this risk such as improvements in care beyond the combination of availability and mandates plus carrying health insurance, it remains to be seen. However, the data is very suggestive. Further evaluation at the national level in varying communities however would be useful, as well as consideration of population level cost benefit analysis.                                 The next article published by Shen et al. in the New England Journal of Medicine entitled Declining Risk of Sudden Death in Heart Failure. They presented data across 40,000 patients from multiple clinical trials over two decades regarding the changing rates of sudden death amongst heart failure patients. Interestingly they noted there was an overall 44% reduction in sudden death rates across these trials over time dating from the 1990s to 2014.                                 In the earliest trials considered, the mortality rate within 90 days after randomization was as high as 2.4% while the most recent trials suggest that that rate is more like 1.0%. This profound decline was attributed to improved usage and prescription of medications early on in the heart failure course, which may modulate outcomes.                                 The relevance of these findings lies in trials that have been published recently and met analysis that we've discussed regarding utility of defibrillators in nonischemic cardiomyopathy or even ischemic cardiomyopathy. The recently published Danish study suggested that ICDs might not confer an equivalent mortality risk as what would have been expected years ago. However, this publication by Shen et al. is particularly provocative because it calls into question whether the same mortality benefit we anticipated from earlier heart failure trials should still be the rubric by which current defibrillator trials are powered.                                 Namely, if we consider that Danish saw the 25% difference in mortality, with a 44% overall reduction in sudden death seen in trials over time for heart failure, seeking a 25% reduction might be excessive. Thus, this highlights the need to potentially power trials for ICDs and the benefit of such ICDs better. This importance of better stratifying better heart failure patients for sudden death risk has been raised in multiple articles this month, including in a review by Holiday et al. in Circulation and in the series of reviews published in Volume 237 of The International Journal of Cardiology.                                 The last article we choose to focus on in the role of sudden death and cardiac arrest was published by Vehmeijer in Circulation: Arrhythmia and Electrophysiology entitled Prevention of Sudden Cardiac Death in Adults with Congenital Heart Disease: Do the Guidelines Fall Short? They reviewed outcomes amongst 26,000 adults with congenital heart disease in light of existing guidelines for risk prediction and prevention of sudden death.                                 They demonstrated that less than half of the patients with sudden cardiac death actually had a guideline basis recommendation for an ICD on the basis of either the 2014 consensus statement on arrhythmias or the 2015 European Society of Cardiology Guidelines. These findings are very provocative in suggesting that we don't really understand who requires treatment amongst adults with congenital heart disease.                                 With improved care paradigms, both with improvements in surgical outcomes as well as ambulatory care of these patients and recognition of need for interventions, arrhythmias are becoming a greater and greater problem amongst patients with adult congenital heart disease. However, large scale studies are limited in stratifying overall risk of arrhythmias. The risk is certainly present as many of these patients have ventricular scar often attributable to cardiac surgeries or have hemodynamic insults that may result in progressive fibrosis of the ventricles.                                 In addition, the basal abnormalities of cardiac formation itself may lend itself to a sudden increased risk of arrhythmias. Thus, the question remains as how to best risk stratify these patients in order to reduce these overall sudden death rates. Changing gears yet again, we'll focus on two articles within the realm of cellular electrophysiology. The first article was published by Cerrone et al. in Nature Communications entitled Plakophilin-2 is Required for Transcription of Genes that Control Calcium Cycling and Cardiac Rhythm.                                 They demonstrated that plakophilin-2, or PKP2, which is known to mediate arrhythmogenic right ventricular cardiomyopathy due to abnormalities in the desmosomes actually has other direct electrical effects independent of substraight effects that are seen. Specifically PKP2 plays a significant role in maintaining gene transcription for several genes that mediate normal electrophysiologic activity, such as the ryanodine receptor, calsequestrin and others.                                 They demonstrated that this reduced expression of other genes secondary to PKP2 absence or abnormality leads to increased isoproterenol or adrenaline-induced arrhythmias that in turn can be suppressed with Flecainide. These findings are provocative in the fact that they suggest that it is possible for patients to have abnormalities of genes such as PKP2 that result in electrical abnormalities independent of the structural abnormalities.                                 Furthermore, it suggests that manifestation of the disease such as catecholaminergic polymorphic ventricular tachycardia may be immediate upstream of typical channels associated with the disease. For example, if PKP2 reduces expression of the ryanodine receptor, this might result in manifestations similar to CPTB in some patients. Along the same lines, Hewitt et al. published in Science Advances regarding deregulated calcium cycling underlies the development of arrhythmia and heart disease due to mutant obscurin.                                 Obscurins are a relatively growing area of interest as these are cytoskeletal proteins that have be associated with both hypertrophic and dilated cardiomyopathy. Similar to the story we just told about PKP2 however, they demonstrated that obscurins, likely through circa 2 and pentameric phospholamban can cause abnormal calcium handling. In fact, they demonstrated that the principle phenotype associated with obscurin abnormalities is one of an electrical abnormality, namely frequent PVCs.                                 In turn, mechanical phenotypes such as cardiomyopathy result in the setting of chronic pathologic stress such as increased afterload, thus these findings demonstrate that genes such as obscurin or PKP2, which are commonly associated with structural or mechanical myopathic processes might have direct independent electrical effects. The story with obscurin raises further question into how this may apply to conditions of PVC-related cardiomyopathy or other such conditions.                                 The other key point about these two areas of interest lie in the fact that it is possible as these genetic abnormalities mediate not just direct substraight elements, but arrhythmogenesis via abnormal channel expression, whether in all patients presenting with such specific genetic abnormalities substraight-based ablation alone will result in reduction of arrhythmia tendency. Of course this remains to be seen and is primarily hypothesis-generating.                                 Next we'll focus on three articles within the area of genetic channelopathies. The first paper was published by Rohatgi et al. in The Journal of the American College of Cardiology entitled Contemporary Outcomes in Patients With Long QT Syndrome. In a large single center practice, they reviewed the results of over 600 patients predominantly affected by LQT1 or LQT2 and demonstrated that after initial evaluation along with treatment based on the individual, done at a highly skilled center, 92% of patients did not experience any breakthrough cardiac events over longterm followup.                                 It was noted however, that the incidence of breakthrough cardiovascular events over longterm followup were far more common in patients who were symptomatic prior to their first evaluation than asymptomatic. In other words, if you were symptomatic prior to your first evaluation, the likelihood of a breakthrough cardiovascular event over longterm followup was as high as 25%, but if you were asymptomatic it was as low as 2%.                                 These data suggest that our overall care of the Long QT patient is improving. However, it also supports that further improvements in care are needed as breakthrough cardiovascular events can continue to occur. It also highlights the importance of close followup of that symptomatic patient in the modern era.                                 The second article was published by Kannenkeril et al. in JAMA Cardiology entitled the Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia. Flecainide currently carries a class 2A indication according to both the 2015 ENC guidelines and 2013 HRS AHRA APHRS consensus statement for treatment of patients with CPVT who fail max dose beta blockers. A lot of this evaluation however, has been based on retrospective evaluations.                                 Kannenkeril reviewed in a prospective single blind placebo controlled crossover trial the effect of Flecainide on exercise associated arrhythmias in CPTV patients who were already on max tolerated beta blockers and had an ICD. Amongst the 14 patients included of whom 13 completed the study, they showed there was a significant reduction in median ventricular arrhythmia score during exercise and in fact there was complete suppression with Flecainide compared to the placebo of 85%.                                 These findings thus add to the existing literature in terms the potential incremental value of Flecainide in achieving adequate arrhythmia suppression when used in conjunction with maximal tolerated beta blockers. The last article within the realm of genetic channelopathies we'll focus on was published by Yang et al. in The Journal of Physiology entitled A Multi-Scale Computational Modeling Approach Predicts Mechanisms of Female Sex Risk in the Setting of Arousal-Induced Arrhythmias.                                 It is recognized that female gender can increase the risk of Torsades in the setting of both inherited and acquired prolonged QT syndromes. In a combination of experimental and computational approaches, Yang et al. demonstrated that hormone concentrations can partly mediate this risk, specifically as it relates to her-related mutations. They demonstrated testosterone and high progesterone levels provide a protective effect against Torsades. However, estrogen can enhance Torsadogenic potential, particularly in the setting sympathetic stress.                                 They also demonstrated the mechanism by which this likely occurs is due to interaction of estrogen with pore loop or intracavity binding site of the her channel. In fact, on top of this they demonstrated that combined treatment with both estrogen and Dofetilide can simultaneously blockade the pore channel of her. These findings are provocative and hypothesis-generating. In terms of potential future research to further clarify risk for patients, particularly as it may apply to menstruating females who might have varying levels of estrogen, especially when being treated with concomitant QT prolonging agents such as Defetilide.                                 Next we will focus on three articles within the realm of ventricular arrhythmias. The first article was published by Sapp et al. in JACC Clinical Electrophysiology entitled Real Time Localization of Ventricular Tachycardia Origin from the Twelve Lead Electrocardiogram. They presented a methodology for rapidly determining in real time the approximate origin of a ventricular tachycardia using the 12 lead during cardiac ablation.                                 In 38 patients they used a variety of methods that involved multiple linear regression learning methods and demonstrated that a patient-specific regression method using at least 10 training set pacing sites in the individual patient can provide a localization accuracy of the exit site for VT of as much as five millimeters. Furthermore, with additional pacing sites that accuracy could improve further.                                 These findings support the continued utility of the standard 12 lead ECG in localizing the exit site of ventricular tachycardia. Furthermore, it points out the importance of considering that the electrocardiogram can be patient-specific. By using multiple pacing sites, this helps an algorithm learn how a patient-specific heart exists in terms of its electrical propagation potential. Further informing based on a 12 lead of a specific VT approximately where it should be exiting from.                                 The next article we will focus on was published by Muser et al. in again, JACC Clinical Electrophysiology entitled Longterm Outcomes of Catheter Ablation of Electrical Storm in Nonischemic Dilated Cardiomyopathy COMpared with Ischemic Cardiomyopathy. The summary point to this article is in a single center, large volume group of patients including about 267 total, the longterm outcomes of VT recurrence or mortality was no different between nonischemic and ischemic patients.                                 This is important to note as most prospective studies and in fact retrospective studies of the role of ventricular tachycardia ablation have focused on ischemic patients where the substraight is relatively predicable. These findings highlight that ablation may provide a reasonably effective therapy irrespective of the cause of the myopathy. Finally, changing gears within the realm of ventricular arrhythmias, we'll focus on a translational article by Motloch et al. in JACC Basic to Translational Science entitled Increased Afterload Following Myocardial Infarction Promotes Conduction-Dependent Arrhythmias That Are Unmasked by Hypokalemia.                                 They studied the role of increased afterload after myocardial infarction in a listing arrhythmias in a porcine infarct model. They demonstrated that in the setting of increased afterload there was increased widespread interstitial fibrosis. Interestingly, pacing -induced arrhythmias induced by a rapid burst pacing were mediated by hypokalemia associated conduction abnormalities rather than repolarization abnormalities.                                 The reason these findings are potentially important lie in the fact that arrhythmias in the early stages after myocardial infarction, especially in a setting of increased afterload, might be considered to be secondary to either repolarization abnormalities or depolarization abnormalities. These findings suggest that in the setting of concomitant hypertension the primary problem really lies in hypokalemia associated conduction abnormalities.                                 Thus, treatments that impair cardiac excitability, for example, even sodium channel blockade, may similarly confer an increased risk of ventricular arrhythmias when in the presence of increased afterload and myocardial infarction. It also calls into question whether interventions such as antitachycardia pacing in patients with hypertension, in other words increased afterload, might be more prone to acceleration of the ventricular arrhythmias than patients who are relatively better managed as far as afterload.                                 Changing gears yet again, we will focus on EP relevant myopathies. [inaudible 00:44:19] et al. published in JACC Clinical Electrophysiology regarding use of the 12 lead electrocardiogram to localize regions of abnormal electron atomic substraight in arrhythmogenic ventricular cardiomyopathy. There were really two major articles in this regard that have been published both in the same month.                                 The other article was published by Andrews et al. in Circulation, Arrhythmia and Electrophysiology entitled Electrical and Structural Substraight of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging.                                 The relevance of both of these articles lies in their statements about the potential utility of noninvasive approaches essentially using electrocardiograms to determine the distribution of substraight in arrhythmogenic right ventricular cardiomyopathy. The article by [inaudible 00:45:16] et al. specifically focused on fractionation of the QRS. They showed that patients with evidence of fractionation in the QRS on a 12 lead ECG had more extensive substraight.                                 Furthermore, distribution of fractionation to specific leads such as inferior, anterior or basal superior leads, was 100% specific, but veritably sensitive for identifying substraight as it localizes to specific cardiac regions. In turn, the publication by Andrews et al. in Circulation, Arrhythmia and Electrophysiology reviewed how the addition of multiple leads by a noninvasive electrocardiographic imaging could be used to even more specifically hone in on the relevant substraights.                                 Their further benefit was in the suggestion that repolarization abnormalities in fact co-localized with origination sites for ventricular ectopy in these patients. In combination, these sites highlight the utility of simple, noninvasive methods of electrocardiographic imaging in identifying and defining the arrhythmogenic substraight in the NRVC.                                 The next article we will review was by Sommariva et al. in Nature's Scientific Reports published just this past month entitled MIR 320A as a Potential Novel Circulating Biomarker of Arrhythmogenic Cardiomyopathy. They did micro RNA analysis on 53 healthy controls, 21 idiopathic VT patients and 36 arrhythmogenic cardiomyopathy patients and demonstrated that the circulating micro RNA 320A was significantly higher in arrhythmogenic cardiomyopathy than in either other cohorts.                                 It is recognized that some patients with idiopathic VT, especially right ventricular [inaudible 00:47:09] VT might reflect a cohort that might have what we call "concealed ARVC." The question thus becomes how to define why a patient has a specific manifestation of disease because longterm outcomes, if there is some underlying ARVC might be worse if the ARVC is not recognized and if cure is assumed based on treatment of the initial presenting rhythm.                                 Thus identifying novel ways of defining the presence of a disease even in the absence of obvious structural abnormalities carries benefit in terms of suggestions on longterm followup. Complimentary to the previously discussed article on the role of PKP2 mutations on mediating electrical instability in the heart, the study by [inaudible 00:48:01] et al. does in fact suggest that there might be methods of distinguishing arrhythmogenic cardiomyopathy from whether it be controls or truly idiopathic ventricular tachycardia using a very specific circulating biomarker.                                 On a completely different route, we'll finish our podcast today with a discussion of Bruner et al. published in European Heart Journal entitled Alcohol Consumption, Sinus Tachycardia and Cardiac Arrhythmias at the Munich Oktoberfest: Results from the Munich Beer-Related Electrocardiogram Workup Study or Munich Brew.                                 Bruner et al. studied over 3,000 voluntary participants with a combination of breath alcohol concentration measurements and electrocardiographic recordings via smartphone throughout the Munich Oktoberfest. In addition, they sought to evaluate chronic alcohol consumption effects on arrhythmias in a separate cord of over 4,000 patients from the Cora S4 study. In the study regarding acute alcohol effects, they demonstrated that in line with increasing BAC, there was a greater occurrence of arrhythmias in particular sinus tachycardia in almost a third of patients.                                 What was even further interesting was that respiratory sinus arrhythmia over the course of higher BAC is from baseline was reduced in the setting of alcohol use. Similarly, with chronic alcohol consumption there was an apparent significant association with the occurrence of sinus tachycardia. The reason these findings are important is in their suggestive element that the effects of alcohol intake in terms of whether it be acute or chronic arrhythmogenesis might somewhat lie in their effects on the basal autonomic states. As demonstrated by the reduction in overall sinus arrhythmia.                                 These findings serve to further elucidate mechanisms by which alcohol may mediate arrhythmias in a large real world patient sample. Thank you for joining us on this edition of On The Beat. Tune in next month again for more articles that might be of interest to the general electrophysiologic community all summarized in a single location.

Dr. Paul Wang:                Welcome to the monthly podcast, On The Beat for Circulation: Arrhythmia, and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field.                                            This month's issue of Circulation: Arrhythmia, and Electrophysiology has a number of groundbreaking and fascinating articles. Let's start with the first article by Christopher Andrews and Associates on the novel use of noninvasive electrocardiographic imaging in patients with arrhythmogenic right ventricular cardiomyopathy.                                            The authors compared 20 genotyped arrhythmogenic right ventricular cardiomyopathy patients to 20 control patients using electrocardiographic imaging, ECGI, a method for noninvasive cardiac electrophysiology mapping. They found that ARVC patients had a longer ventricular activation duration, with a mean of 52 milliseconds versus 42 milliseconds with a p-value of 0.007, as well as a prolonged mean epicardial activation recovery interval, a surrogate for local action potential duration with a median of 275 milliseconds versus 240 milliseconds with a p-value of 0.014.                                            In addition, the authors observed abnormal epicardial activation breakthrough locations with regions of nonuniform conduction and fractionated electrograms. These abnormal activation patterns correlated with late gadolinium enhancement using cardiac magnetic resonance scar imaging. This study suggests that electrocardiographic imaging may be a promising tool for the diagnosis and follow-up of patients with ARVC.                                            In the next article, Thomas Fink and Associates report the results of the prospective randomized Alster-Lost AF trial, comparing ablation strategies in patients with symptomatic persistent or long-standing persistent atrial fibrillation. The study compared standalone pulmonary vein isolation, the PVI-only approach, with a stepwise approach of PVI followed by complex fractionated atrial CFAE ablation and linear ablation, the substrate modification approach. Patients were randomized one-to-one to each study group. The primary study endpoint was freedom from recurrence of any atrial tachyarrhythmia at 12 months after a 90-day blanking period. 118 of 124 enrolled patients were analyzed. 61 in the p-value only group and 57 in the substrate modification group. The pulmonary vein isolation only group had a one-year freedom from arrhythmia recurrence of 54%, which was similar to the 57% recurrence rate in the substrate modification group, p = 0.86. Thus, this study confirms in a population of persistent and long-standing persistent atrial fibrillation that there is no significant benefit to the addition of CFAE ablation to pulmonary vein isolation only.                                            In the next paper, John Papagiannis and associates studied AV nodal reentrant tachycardia in patients with congenital heart disease. In this multi-centered, retrospective study, the authors compared catheter ablation of AV nodal reentrant tachycardia in 51 patients with complex congenital heart disease, with 58 patients with simple congenital heart disease.                                            There was no significant difference between the groups in terms of growth parameters, the use of 3D imaging, or type of ablation, radio frequency versus cryoablation. The procedure times, fluoroscopy times were longer in the complex group compared to the simple group. There were also significant differences between the groups in terms of acute success of ablation, 82% versus 97%; the risk of AV block, 14% versus 0%; and the need for chronic pacing, all significant in favor of the simple congenital heart disease group. There were no permanent AV block observed in patients who underwent cryoablation.                                            After a mean, 3.2 years of follow up, the long-term success was 86% in the complex group, and 100% in the simple group, p = 0.004. Thus, the authors concluded that the complexity of congenital heart disease affects the outcome of AV nodal reentrant tachycardia catheter ablation.                                            In the next paper, Moloy Das and associates studied whether the presence of abnormal intra-QRS peaks would indicate altered activation and might predict ventricular arrhythmias in cardiomyopathy patients. The authors examined the 99 patients with ischemic or nonischemic cardiomyopathy undergoing primary prevention ICD implantation, with a mean left ventricular ejection fraction of 27%. After a median follow up of 24 months, 20% of patients had arrhythmic events. Using a multivariate, Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRS peaks, only QRS peaks was an independent predictor of arrhythmic events with a hazard ration of 2.1. ROC analysis revealed that a QRS peak value of greater than or equal to 2.25 identified arrhythmic events with a greater sensitivity than QRS duration, 100% versus 70%, with p < 0.05, and a negative predictive value of 100%, compared to 89% for QRS duration, p < 0.05. Thus, the authors concluded that this novel QRS morphology index may be a promising additional tool in sudden death risk stratification.                                            In our next paper, Yoshiyasu Aizawa and associates studied J wave changes during atrial pacing in patients with and without idiopathic ventricular fibrillation. In eight patients with idiopathic ventricular fibrillation, and 17 patients without idiopathic ventricular fibrillation, having J waves, the J wave amplitude was measured before, during and after atrial pacing. All of the patients with ventricular fibrillation did not have any structural heart disease. The idiopathic ventricular fibrillation patients were younger than the non-idiopathic ventricular fibrillation patients, and had larger J waves with more extensive distribution. The J wave amplitude decreased from 0.35 millivolts to 0.22 millivolts when the R-R intervals shortened, a decrease of greater than, equal to 0.005 millivolts in the J wave amplitude was observed in six of eight idiopathic ventricular fibrillation patients while the J wave amplitudes were augmented in nine out of 17 non-idiopathic ventricular fibrillation subjects. The authors therefore concluded that the different response patterns of J waves to rapid pacing suggested different mechanisms that is early repolarization in idiopathic ventricular fibrillation patients, and conduction delay in non-idiopathic ventricular fibrillation patients.                                            Our final paper of the month was written by Jim T. Vehmeijer and colleagues, who examined the utility of recent guidelines and consensus documents for ICD implantation for sudden death protection in adults with congenital heart disease. The authors examined an international, multi-center registry, having 25,790 adult congenital heart disease patients, and identified all sudden cardiac death cases, which were then matched to living controls by age, gender, congenital defect and surgical repair. They used conditional logistic regression models to calculate odds ratios, and receiver operating characteristic curves. In their first analysis, they identified 124 cases and 230 controls. In total, 41% of sudden cardiac death cases, and 17% of controls had an ICD recommendation based on the 2014 consensus statement on arrhythmias in adult congenital heart disease, with an odds ratio of 5.9. A similar analysis of the 2015 European Society of Cardiology guidelines showed that 35% of cases and 14% of controls had an ICD recommendation, respectively with an odds ratio of 4.8. The authors concluded that a minority of sudden cardiac death cases had an ICD recommendation according to these guidelines, while the majority of sudden cardiac death victims remained under-recognized, emphasizing the need for continued critical, clinical reasoning when deciding on ICD implantation in adult congenital heart disease patients.                                            And now, here with the review of the highlights from the articles from journals throughout the world, in the past month is Dr. Suraj Kapa. Dr. Suraj Kapa:                 Thank you, Paul. Today we'll be discussing hard-hitting articles that have been published within the last month across the electrophysiologic literature. First, we'll be focusing on the topical area of atrial fibrillation, with an initial foray into the realm of anticoagulation. The first article we will be focusing on was published by Yao, et al., in the Journal of the American College of Cardiology in volume 69, entitled Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients with Atrial Fibrillation and Renal Dysfunction. In the study, Yao, et al, demonstrated that the dosing of direct oral anticoagulants in a real world patient sample, with preexisting renal dysfunction was inappropriately dosed in as many as 43% of patients. Specifically, in these patients, there was overdosing of the direct oral anticoagulants. Moreover, as many as 13% of patients were underdosed.                                            The overdosing of these patients led to increased bleeding risks, without an incremental stroke benefit compared with cohorts that were appropriately dosed. In turn, underdosing led to increased stroke risk without an incremental reduction in bleeding risk. These results are provocative in that they indicate, in a real life sample of patients, frequent inappropriate dosing of direct oral anticoagulants. This identifies the need for better guidelines, or better adherence to guidelines, in management of these patients to improve clinical outcomes.                                            In another article with the realm of anticoagulation management of atrial fibrillation patients, was published by Labovitz, et al. in Stroke, in volume 48, entitled Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy. They demonstrated in a small randomized study that a smart phone based artificial intelligence program could be used to monitor anticoagulation adherence, and in fact, improve it. The program utilized features available on all smart phones to identify the patient, the medication, and active ingestion of the medication by the patient in real time.                                            With this approach, they noted the plasma drug concentration levels indicated 100% adherence in the intervention group, namely those using the artificial intelligence program, while in the control group, only 50% of patients had adherence to the medications. Overall, there was an absolute improvement in adherence amongst patients on direct oral anticoagulants by as many as 67%. These findings are provocative given data suggestive of the lack of appropriate adherence to anticoagulant therapy amongst patients.                                            Changing paths from anticoagulation management, the next article we choose to focus on was published within the realm of cardiac mapping in ablation for atrial fibrillation. It was published by Das, et al. in JACC: Clinical Electrophysiology in volume three, entitled Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms, The PRESSURE Randomized Controlled Trial. In this randomized trial, Das, et al, demonstrated that aggressive reevaluation of patients undergoing pulmonary vein isolation after index ablation for pulmonary vein reconnection, with the intent to re-ablate, significantly reduced arrhythmia recurrence. In addition, there was a commented improvement in quality of life. It has been well-recognized that even in the absence of clinical recurrence, a large number of patients, after index pulmonary vein isolation, may have pulmonary vein reconnection. However, it has always been unclear whether aggressive reevaluation and re-isolation of reconnected veins holds value, has been unclear. Further study is needed to evaluate the cost effectiveness and the risk-benefit ratio of such an invasive approach to reevaluate pulmonary vein isolation, irrespective of the evidence of clinical atrial fibrillation recurrence, however.                                            Changing gears, with the realm of atrial fibrillation, we will now focus on risk stratification and management. Pathik, et al, in JACC: Clinical Electrophysiology, published in volume three, have progressed to complement their work on the role of risk stratification, and risk factor management in patients with atrial fibrillation, to evaluate the cost-effectiveness and clinical effectiveness of such risk factor management clinics in atrial fibrillation, that they termed the SENSE Study. They demonstrated that there was significant cost and clinical benefits to aggressive risk factor targeting clinics for patients with atrial fibrillation, specifically, utilizing supervised approaches to weight-loss, improvements in fitness and reduction in other clinical risk factors such as diabetes, hypertension, or other risks. The patients had a significantly decreased risk of arrhythmia occurrence. In addition to this, there was an actual incremental cost benefit of $62,000 for quality adjusted life year saved. These findings suggest that such an aggressive risk factor mediated approach to management of patients with atrial fibrillation holds significant promise, not just in the reduction of arrhythmia occurrence, but also in potential healthcare cost savings.                                            Our next article within the realm of risk stratification and management relates to identification of patients with atrial fibrillation, in otherwise normal population-wide cohorts. Krivoshei, et al, in Europace volume 19, studied algorithms applied to information gathered on pulse-wave signals via smartphone-based LED light/camera lens. They demonstrated that using such a tool on patients, atrial fibrillation can be discriminated from sinus rhythm with sensitivity specificity of above 95%. We recognize the critical importance of early detection of atrial fibrillation, particularly in high-risk cohorts for stroke. Early identification of patients may identify those patients for initiation of anticoagulation, even if asymptomatic or minimally symptomatic. Our so-termed subclinical atrial fibrillation patients, which we identify by prior clinical trials, have an increased risk of stroke. However, the main hurdle to implementation of such technology has been the high cost, applied to traditional medical interventions. However, use of ever-advancing ambulatory technologies, such as smartphones or in the future, smart watches, may held the promise to identify atrial fibrillation via cheaper mechanisms.                                            The last article within the realm of atrial fibrillation risk stratification and management that we'll choose to focus on is that by Gaeta, et al, published in Europace in volume 19. They performed a systematic review and meta-analysis of existing trials, regarding whether epicardial fat depot was associated with atrial fibrillation. They demonstrated via their meta-analysis that there is, in fact, a significant association between epicardial fat and atrial fibrillation risk, with more epicardial fat being associated with more persistent, rather than paroxysmal forms of atrial fibrillation, as well as any atrial fibrillation versus none. However, the role of epicardial fat in arrhythmogenesis remains unclear. While many studies suggest an association, causation remains to be proven. A recent review, however, published by Antonopoulos, et al, in the Journal of Physiology in June 2017, has multiple suggestive pathways by which paracrine effects of epicardial fat on the heart and vice versa, may lead to alterations in normal cardiac function. Thus, while this remains an association, there are evolving principles that might further support causation.                                            Changing topics, we'll next focus on four major articles within the realm of ICDs, pacemakers, and CRT managements. Lyons, et al, in JACC: Heart Failure, volume five, studied the impact of current versus previous cardiac resynchronization therapy guidelines on the proportion of patients with heart failure eligible for therapy. They evaluated the effect of changing guidelines based on increased bodies of evidence, related to indications for resynchronization therapy on real world patient samples. They demonstrated that these further refined guidelines would decrease by as many as 15% those patients eligible for cardiac resynchronization therapy. However, while their study demonstrates that fewer patients may qualify, as far as receiving benefit from resynchronization therapy, at least two studies published in the same month have demonstrated that even amongst patients who meet guidelines, there is severe under-utilization/under-referral for such devices. These studies by Marzec, et al, in JAMA Cardiology, as well as by Randolph, et al, in American Heart Journal, demonstrated that there's frequent under-utilization and under-referral of patients meetings indications for resynchronization therapy.                                            Keeping on the same topic in resynchronization therapy, Barra, et al, in Heart, volume 103, looked at sex-specific outcomes with addition of defibrillation to resynchronization therapy in patients with heart failure. They demonstrated in a multi-central observational cohort study that the addition of defibrillator resynchronization therapy in patients meeting primary prevention indications for device implant, primarily conferred benefit in men, rather than women. In the same month, Randolph, et al, in the American Heart Journal, demonstrated that resynchronization therapy offered potential greater benefits in women over men. Interestingly, this study by Barra, et al, conversely demonstrates that the concomitant addition of defibrillator therapy does not necessarily further improve outcomes on women, with the primary benefit being conferred to men. Whether this differential is effected by relative rates of arrhythmogenic myopathy is in men versus women remains unclear. However, the findings are provocative.                                            Keeping within the realm of appropriateness of defibrillator therapies, Luni, et al, performed a meta-analysis of randomized controlled trials published in the Journal of Cardiovascular Physiology, in volume 28, on the mortality effect of ICDs in primary prevention in nonischemic cardiomyopathies, including six studies that met criteria. They found that while there was an overall significant survival benefit in patients receiving ICDs in the setting of nonischemic cardiomyopathy. Once accounting for those on adequate beta-blockade, and ACE or ARP 00:22:56 therapy, there was no statistical difference conferred by primary prevention ICD use.                                            This complements an article published by Al-Khatib, et al, in JAMA Cardiology, in the same month, which also suggested that the overall mortality benefit was present in nonischemic patients, though in their case, they did not evaluate the granularity of appropriateness based on current management at the time of ICD implant. These findings further previous findings from a Danish study that the survival benefit of primary prevention ICD in nonischemic cardiomyopathy might not be anywhere near the same as those conferred with ischemic cardiomyopathy. However, the perceived lower relative mortality benefit, compared to earlier clinical trials, namely partly due to improvements in the clinical and pharmacologic management of such patients.                                            The final paper we'll choose to focus on within the realm of device therapies was published by Doppalapudi, in the Journal of Cardiovascular Electrophysiology, in volume 28. They looked at the significant discrepancy between estimated and actual longevity in St. Jude Medical implantable cardioverter defibrillators. While amongst a small number of patients of only 40, they demonstrated that up to 74% of these patients had a significant discrepancy between actual and estimated battery life, specifically amongst current or promotes defibrillator devices. This discrepancy was most significant in the 18 months prior to reaching electrical replacement medication. These findings suggest the need for more frequent monitoring of such devices to look for rapid battery depletion.                                            Switching topics away from device therapies, we next focus on the realm of sudden death in cardiac arrest. The first paper we'll focus on was published in Circulation, in volume 135, by Halliday, et al, and focused on the association between mid-wall late gadolinium enhancements, and sudden cardiac death in patients with dilated cardiomyopathy in mild and moderate left ventricular systolic dysfunction. In his publication, Halliday demonstrated that the presence of mid-wall late gadolinium enhancements on MRI identified patients at risk of sudden cardiac death, with a hazard ratio up to 35.9 for border sudden cardiac death, amongst dilated cardiomyopathy patients with such mid-wall dilated enhancements. The incremental value of MRI is evolving in the risk stratification of patients, though it has not quite met inclusion in guidelines for decision making regarding those who most benefit from ICDs. However, studies like this are provocative in the sense of identifying those patients most at risk.                                            Within the realm of cardiac arrest, we next focus on the role of out-of-hospital cardiac arrest, and how to improve management of these patients. Boutilier, et al, published in Circulation, in volume 135, optimization of drone networks to deliver automated external defibrillators. They demonstrated via simulation model that using a drone network system to deliver AEDs to patients suffering sudden cardiac arrest could decrease the time to response by as much as six minutes and 43 seconds compared to traditional approaches, such as 911 in urban areas, or as much as 10 minutes and 34 seconds in rural areas. These findings are highly provocative. However, they need to be applied to clinical real world situations. The first attempt at such was actually published this month as well, by Claesson, et al, in the Journal of the American Medical Association, and demonstrated the feasibility of implementing a drone network within real world case example, and the efficacy of the same. These disruptive technologies have the potential to improve emergency care, and out of hospital cardiac arrest survival.                                            Next, we move on to studies in electrophysiology. The first article we will focus on is by De Jesus, et al, published in Heart Rhythm, volume 14, on antiarrhythmic effects of interleukin 1 inhibition after myocardial infarction. De Jesus, et al, in this study, demonstrated that the use of anakinra and interleukin 1 beta antagonist would improve conduction velocity, calcium handling, spontaneous and inducible ventricular arrhythmias, and action potential duration dispersion, in canine models. These findings of potential antiarrhythmic effects were due to increased expression of connexin 43, and sarcoplasmic reticulum calcium ATPase. While in isolation, this might seem a general article, it complements multiple recent studies that suggest a significant role for targeting inflammatory pathways, not just in infarct pathogenesis, but in arrhythmogenesis.                                            Lazzerini, et al, this month as well, demonstrated in the European Heart Journal, the link between systemic inflammation and arrhythmic risk based on a review of the existing literature. In addition, Yucel, et al, demonstrated in Nature Scientific Reports the relationship between lipopolysaccharides and electrophysiology dysfunction in stem cell direct cardiomyocytes, which they felt partly may be mediated through interleukin pathways. Finally, though as of yet unpublished, a clinically available interleukin 1 beta inhibitor, canakinumab, has been shown in preliminary data to reduce major cardiovascular events in a randomized, double-blind, placebo-controlled trial, when combined with optimal medical therapy in patients with post myocardial infarction. These potential clinical benefits complement translational benefits seen to date. However, whether these are conferred by primary inflammatory pathways, arrhythmogenic pathways, or interactions between both remains to be seen.                                            The next article we will focus on is by Chauveau, et al, published in Circulation: Arrhythmia Electrophysiology, volume 10. They looked at induced pluripotent stem cells derived cardiomyocytes in producing in vivo biological pacemaker function. They demonstrated that in canines with atrioventricular block, injection of such derived cardiomyocytes into the epicardial surface of the heart, demonstrated inherent pacemaker activity with global cardiac activation. In fact, this activation in pacemaker activity increased over time, up to four weeks of maturation, and also demonstrated responsiveness to epinephrine and alterations with day and night variation. However, the intrinsic rates tend to be quite low, in the 50 to 60 beat per minute range. The potential to restore pacemaker activity in patients with severe conduction disease, holds the potential to dynamically progress options in care for patients with electrophysiologic disease. However, even though these findings are promising, significant remaining questions include ensuring the robustness of the heart rate conferred by these biologic pacemakers, the durability of pacemaker activity, and the arrhythmogenic potential of such interventions.                                            Within the realm of cellular electrophysiology, the final article we will choose to focus on was published by Barbic, et al, in American Journal of Physiology, heart and Circulatory Physiology, in volume 312, entitled Detachable Glass Microelectrodes for Recording Action Potentials in Active Moving Organs. They demonstrated that a new glass microelectrode could allow for determinational cellular actional potential duration in actively moving organs. This is a profound potential advance in the physiologic evaluation of both in vitro and in vivo translational cellular models of cardiac activation. Traditional patch clamping action potential studies required immobilization of cells being studied, whether by mechanical or pharmacologic means. However, directed efforts to immobilize cells can alter electrophysiologic parameters. The ability to record cellular action potentials in actively moving cells, for example the beating heart, may offer studies of cellular electrophysiology, that more closely approximate real world physiology.                                            Our next area of focus will be on genetic channelopathies, including long QT syndrome, Brugada, catecholaminergic polymorphic ventricular tachycardia and others. The article we choose to focus on this month, within this realm, was published by Pappone, et al, in Circulation: Arrhythmia and Electrophysiology, volume 10. They focus on electrical substrate elimination in 135 consecutive patients with Brugada syndrome. They demonstrated in this large cohort of patients that the arrhythmogenic electrical substrate associated with the Brugada syndrome primarily localized to the right ventricular epicardium, and an ablation of such region led to normalization of electrocardiogram and non-inducibility ventricular arrhythmias acutely in all patients, and over a long term in all but two patients.                                            These findings complement prior work by Nademanee and others that support a role for targeting substrate in the region of the right ventricular epicardium, in preventing recurrent ventricular arrhythmias in patients with Brugada syndrome, and in normalizing the electrocardiographic Brugada pattern. At the translational level, prior work has demonstrated that the same SCN mutations associated with Brugada syndrome confer accentuated transmittal gradients within the realm of the right ventricle, along with preferential prolongations of action potentials in the right ventricular epicardial myocytes. However, it remains to be seen whether the specific genetic cause of individual patient's Brugada pattern or Brugada syndrome is associated with discreet pathologic and inter-ablation findings and success rates.                                            Next, moving on to the realm of ventricular arrhythmias, we focus on three major articles published in the past month. The first article is published by Vaseghi, et al, in the Journal of the American College of Cardiology, volume 69, entitled Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. They demonstrated that cardiac sympathetic denervation may be an effective therapy in many patients with intractable ventricular arrhythmias, with a greater than 50% reduction in sustained VT, ICD shock, transplant or death over one year follow-up. Not only this but nearly one third of patients no longer required antiarrhythmics. However, bilateral sympathectomy is far superior over left sided only sympathectomy. Furthermore, advanced heart failure and VT cycle length were associated with poor outcomes. These findings suggest a role for bilateral sympathectomy in management of patients presenting with intractable ventricular arrhythmias. However, patient identification and selection in terms of the ideal cohorts for such therapy, and how to identify such cohorts remains to be seen.                                            Our next article regards advances in attaining epicardial access. Di Biase, et al, published in Heart Rhythm, volume 14, the initial international multi-centered human experience with the novel epicardial access needle embedded with a real time pressure frequency monitor to facilitate epicardial access. They looked specifically at feasibility and safety of this novel approach. While in only 25 patients, they did demonstrate that epicardial access can be successfully obtained with only one complication of a delayed pericardial effusion. With evolving indications for epicardial access, including for left atrial appendage occlusion, epicardial ganglia modulation, and ventricular arrhythmia mapping and ablation, development of novel tools to minimize the risks associated with epicardial ablation, particularly in individuals who do not perform it routinely, is critical. However, whether these variable approaches hold significant advances in randomized trials, beyond traditional approaches, remains to be seen.                                            Within the realm of ventricular arrhythmias, the last article we will choose to focus on was published by Acosta, et al, in Europace, volume 19. They looked at the long-term benefit of first line peri-implantable cardioverter-defibrillator implant ventricular tachycardia substrate ablation in secondary prevention patients. This study complemented prior data from SMASH-VT supporting a role for early ablation to reduce future arrhythmia events in patients receiving defibrillators. In their study, they demonstrated that early ablation was associated with a decreased recurrence of ventricular arrhythmias and defibrillary shocks over an average of almost four years. However, it addressed patients with lower ejection fractions, namely less than 35%, received less benefit. Though this was mostly conferred by while having similar frequency of VT recurrence, having an overall lower burden compared to those who did not have ablation. Practice patterns continue to vary in the decision making with regards to performing early ablation in such patients. Furthermore, whether or not a mortality benefit exists with early ablation remains relatively unclear and unproven. However, there's an evolving body of evidence to support the notion that aggressive, early intervention with invasive procedures in patients receiving ICDs, and at high risk for ventricular arrhythmias, may make sense.                                            The final article we will focus on that has been published in the past month, is published by Turagam, et al, in the International Journal of Cardiology, volume 236, entitled Practice Variation in the Re-initiation of Dofetilide: an Observational Study. Turagam, et al, surveyed 347 providers in the U.S. and worldwide, and demonstrate significant practice variability when re-initiating dofetilide. They know that up to 21% of providers always admit patients to the hospital for dofetilide re-initiation, while 37% of physician admit patients less than 10% of the time. Interestingly, the duration off of dofetilide ranging anywhere from three days to more than a year, did not necessarily significantly affect the rate of decision to re-initiate dofetilide, after prior cessation. One key finding of this was the 4% of physicians reporting major adverse events with drug re-initiation in patients. This was despite the vast majority of these patients tolerating de novo initiation. Given the prolific effects of antiarrhythmetic drugs, strategies to reduce those potential risks are critical. In fact, multiple groups such as the Cardiac Safety Research Consortium, within the same month, had sought to publish recommendations for long-term electrocardiographic monitoring, in drug developments. It must be realized the consideration of the impact of antiarhythmetic drug managements may not always be well outlined by existing protocols. And thus, further study is likely required to inform current clinical practice.                                            It was my pleasure to introduce to you some of the major heart hitting articles published in the part month across the electrophysiologic literature. While none of this is really touching on every single major advance, we hope to identify those that hold potential, measure immediate clinical potential, or those that hold potential for future advancements within our field. Thank you. Dr. Paul Wang:                I hope you enjoyed this month's podcast On the Beat, Circulation: Arrhythmia and Electrophysiology. We've had a number of groundbreaking and fascinating studies. See you next month.

Dr. Paul Wang:                Welcome to the monthly podcast, On the Beat, for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor in Chief with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field. Hey, Suraj. How are you doing? Dr. Suraj Kapa:                 Hey, Paul. I'm doing great. How are you? Dr. Paul Wang:                Really good. I'm happy to talk to you today and we're happy to launch this new podcast for circulation, arrhythmia, and electrophysiology. Dr. Suraj Kapa:                 I'm really excited that we're going to be able to update the field. Everything you're doing, summarizing all the great articles that you're publishing in circulation, arrhythmia, and electrophysiology each month I think is really going to offer our readers a great way to keep up with the journal. Dr. Paul Wang:                Yeah, Suraj, I'm really excited you'll be serving all the journals for the latest in topics in our field. I know how hard it is for electrophysiologists to keep track of all the key articles, and you'll be summarizing them for us on the podcast. This will be a really great way for people to stay up to date. Dr. Suraj Kapa:                 Yeah, I think this will really make circulation, arrhythmia, and electrophysiology the go-to place. It'll really offer everybody the opportunity to just keep up to date and also to perhaps interact with one another down the road about what's going on within our field. Dr. Paul Wang:                Yeah, Suraj, I couldn't have said it better. I think it's going to be an easy way to stay in touch with the latest advances in our field. I want to remind everybody to download the podcast, On the Beat.  

On the twenty second episode of Neo Kobe Pizza, we sit down to discuss the historical context of gaming narratives and how games learn lessons from historical evolution, not all of them good. We ruminate on how characters and franchises evolve relative to the popular storylines in fiction of their time, how games learn lessons from fiction over time, and some of the less positive lessons gaming narratives have incorporated into their own narratives along the way. Hosted by Mark B Writing, featuring Paul Wang. (Originally recorded 12/01/16)

Three distinguished experts help us understand autism. Dr. Paul Wang is the Senior Vice President for Medical Research with Autism Speaks. Dr. Andrea Roberts is from the Harvard T. H. Chan School of Public Health. And Dr. Jay Gargus is the Director of Center for Autism Research and Translation at the UCI School of Medicine.

Discover how her autism helped Dr. Temple Grandin revolutionize animal science when she sits down with Neil deGrasse Tyson. Featuring Chuck Nice, Dr. Paul Wang of Autism Speaks, and Paul Shapiro of the Humane Society.

Like Autism Live on Facebook at facebook.com/autismlive   Today on Autism Live, Shannon talks with Dr. Paul Wang, Autism Speaks' senior vice president and head of medical research, about the ground breaking initiative Autism Speaks has launched to further research into the brain-gut connection.  Dr. Wang discusses the importance of further research in GI issues in regards to Autism.  Matt Asner, the Executive Director of the Southern California Chapter of Autism Speaks shares some of the events they are prepping for Autism Awareness Month including Light Up the Blues, Light it Up Blue events, the Los Angles Walk and a number of sporting events sponsored by area baseball, basketball and hockey teams!     Autism Live is a production of the Center for Autism and Related Disorders (CARD), headquartered in Tarzana, California, and with offices throughout, the United States and around the globe. For more information on therapy for autism and other related disorders, visit the CARD website at http://centerforautism.com

Like Autism Live on Facebook at http://facebook.com/autismlive    Dr. Paul Wang, Autism Speaks' senior vice president and head of medical research, speaks about the ground breaking initiative that has been launched to further research into the brain-gut connection.  For a long time Autism parents have suggested that there is a link between GI issues and Autism.  Dr. Wang discusses the importance of further research in GI issues in regards to Autism, so science and medicine can catch up to what parents have been reporting.   Autism Live is a production of the Center for Autism and Related Disorders (CARD), headquartered in Tarzana, California, and with offices throughout, the United States and around the globe. For more information on therapy for autism and other related disorders, visit the CARD website at http://centerforautism.com

Paul Wang and Anne Dubin talk about the risks of heart rhythm disorders both in adults and young children and the common methods used to combat such diseases. (October 4, 2011)