Podcasts about pvcs

Let's start your week strong with a quick tip you can incorporate right away. In this Mo's Monday Minute shortie episode, I'm talking about  what to do when your patient is having premature ventricular contractions (PVCs). We'll talk about key assessments, when to get worried, and important nursing interventions. ___________________ FREE CLASS - If all you've heard are nursing school horror stories, then you need this class! Join me in this on-demand session where I dispel all those nursing school myths and show you that YES...you can thrive in nursing school without it taking over your life! 20 Secrets of Successful Nursing Students – Learn key strategies that will help you be a successful nursing student with this FREE guide! All Straight A Nursing Resources - Check out everything Straight A Nursing has to offer, including free resources and online courses to help you succeed!

A large trial in cardiac pacing finally published, PVCs and cardiomyopathy, cannabis, CV risk and the danger of observational studies, and the tale of two disparate statin trials are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I BioPace Trial Trial manuscript https://doi.org/10.1093/europace/euaf029 II Another Belief Challenged in EP this week—PVCs and CM ‘ UC Paper https://doi.org/10.1016/j.jacep.2025.01.004 JACC Review https://doi.org/10.1016/j.jacc.2024.03.416 Lee et al https://heart.bmj.com/content/105/18/1408 III Cannabis and CV Risk Cannabis and MACE in JACC Advances: https://www.jacc.org/doi/10.1016/j.jacadv.2025.101698 Zeraatkar –Grilling the data https://doi.org/10.1016/j.jclinepi.2024.111278 PLOS-1 10.1371/journal.pone.0199705 IV Cardio-oncology Jacc Onc Substdy https://www.jacc.org/doi/10.1016/j.jaccao.2024.11.008 Editorial https://www.jacc.org/doi/10.1016/j.jaccao.2025.01.006 STOP CA JAMA 2023 https://jamanetwork.com/journals/jama/fullarticle/2807988 PREVENT https://evidence.nejm.org/doi/10.1056/EVIDoa2200097 You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In today's episode, we explore a tragic but educational case involving a 15-year-old girl who suffered severe inhalation injury following a house fire. While heroically rescuing her brother and his friend, she endured prolonged cardiac arrest and severe multi-organ dysfunction. We'll focus on the pathophysiology, investigation, and management of inhalation injuries, including the critical role of recognizing carbon monoxide and cyanide poisoning in these complex cases.Key Learning Points:Exposure to house fire and prolonged cardiac arrestSigns of inhalation injury and airway compromisePathophysiology of inhalation injuries and their impact on multiple organ systemsManagement strategies for inhalation injury, including airway protection and ventilationDifferentiating carbon monoxide and cyanide poisoning in pediatric fire victimsCase PresentationA 15-year-old previously healthy girl is brought to the Pediatric Intensive Care Unit (PICU) after experiencing cardiac arrest during a house fire. She was found unconscious by firefighters after a heroic rescue attempt where she saved her brother and his friend. Upon arrival at the hospital, she was unresponsive, intubated, and in severe cardiovascular distress with signs of multi-organ dysfunction.Key findings include:Soot deposits and superficial burns on extremitiesProlonged resuscitation (45 minutes of field CPR and 47 minutes of in-hospital CPR)Cardiovascular compromise with PVCs, cool extremities, and delayed capillary refillMetabolic acidosis, AKI, coagulopathy, transaminitisSevere hypoxic-ischemic encephalopathy on EEGThese findings raise immediate concern for inhalation injury, which is the primary focus of today's discussion.Pathophysiology of Inhalation InjuryWhen a patient is exposed to smoke and hot gases during a fire, inhalation injury results in significant damage to the respiratory system. Inhalation injury has three main components:Upper airway involvement – Thermal injury can cause swelling and obstruction.Chemical pneumonitis – Noxious chemicals like carbon monoxide and cyanide trigger inflammation in the lungs.

William H. Sauer, MD, FHRS, CCDS, Brigham and Women's Hospital is joined by Edward P. Gerstenfeld, MD, MS, FHRS, University of California, San Francisco, and Yasser Rodriguez, MBA, MD, Cleveland Clinic Florida to discuss; Background: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. Conclusions: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.   https://www.hrsonline.org/education/TheLead https://doi.org/10.1016/j.jacep.2024.01.021 Host Disclosure(s): W. Sauer: Honoraria/Speaking/Consulting: Biotronik, Biosense Webster, Inc., Abbott, Boston Scientific, Research: Medtronic    Contributor Disclosure(s): E. Gerstenfeld: Honoraria/Speaking/Teaching: Abbott, Biosense Webster, Inc., Boston Scientific, Medtronic, Membership on Committees/Advisory Boards: Boston Scientific, Farapulse, Honoraria/Speaking/Consulting: Boston Scientific, Abbott Medical, Medtronic, Adagio Medical, Research: Boston Scientific Y. Rodriguez: Nothing to disclose.   This episode has .25 ACE credits associated with it. If you want credit for listening to this episode, please visit the episode page on HRS365     https://www.heartrhythm365.org/URL/TheLeadEpisode66

Preventricular Contractions (PVCs) by Albuquerque Fire Rescue

Deep-Learning Models for the Prognostication and Localization of Premature Ventricular Contractions Using a 12-Lead Electrocardiogram Guest: Guru G. Kowlgi, M.B.B.S. Host: Anthony H. Kashou, M.D.    In this episode, learners will understand what premature ventricular contractions are. They will learn to differentiate benign rom malignant PVCs, and understand which patients are at risk for PVC-cardiomyopathy. Furthermore, they will gain knowledge about the traditional and novel tools for risk-stratifying patients with PVCs, and how we manage these patients.   Topics Discussed What are PVCs and what are their clinical implications? When should we be concerned about a patient with PVCs? What are some of the tools we have to detect and localize high risk PVCs? How does AI help in this regard? What are the available treatment modalities for managing PVCs? Connect with Mayo Clinic's Cardiovascular Continuing Medical Education online at https://cveducation.mayo.edu or on Twitter @MayoClinicCV and @MayoCVservices. LinkedIn: Mayo Clinic Cardiovascular Services Cardiovascular Education App: The Mayo Clinic Cardiovascular CME App is an innovative educational platform that features cardiology-focused continuing medical education wherever and whenever you need it. Use this app to access other free content and browse upcoming courses. Download it for free in Apple or Google stores today! No CME credit offered for this episode. Podcast episode transcript found here.

This episode of "Heart to Heart with Anna" features a very special heart mom. Kelsi Rogers talks about the surprising circumstances around her son's heart condition. Born with an electrical problem in his heart, Jett has already faced life-and-death situations several times in his short life. Not even three years old yet, he has undergone an ablation and an open-heart surgery.Tune in to find out what kind of heart defect Jett has, why the ablation was so extensive, and what kind of surgery eventually saved his life.Following the interview with Kelsi Rogers, co-editors Megan Tones and Anna Jaworski read the last half of Chapter Seven: Facing My Mortality from their new book The Heart of a Heart Warrior Volume Two: Endurance.Links mentioned in this podcast:HeartFelt: https://www.facebook.com/heartfeltscreeningTiny Tickers Trot: https://runsignup.com/Race/Events/CA/Chico/TinyTickersTrotBaby Hearts Press: https://www.babyheartspress.com (for more information on the book The Heart of a Heart Warrior and more!)To sign up for a Baby Hearts Press Book Study, visit our website here: https://www.babyheartspress.com/volume-2Become a Supporter of the Podcast: https://www.buzzsprout.com/62761/supporters/newSupport the showAnna's Buzzsprout Affiliate LinkBaby Blue Sound CollectiveSocial Media Pages:Apple PodcastsFacebookInstagramMeWeTwitterYouTubeWebsite

In this episode of Heart to Heart with Anna we welcome Frank Jaworski back to the program. Frank shares information about anesthesia when patients go to the electrophysiology lab (EP lab), especially when they need to undergo an ablation.Frank is a certified, registered nurse anesthetist (CRNA) and he has been delivering anesthesia for over 23 years. One of his favorite departments to work with is the EP lab. In this episode, Frank shares some tips to help those in the congenital heart defect community reduce their concerns when visiting the EP lab, he offers some helpful questions patients can ask their anesthesia providers, and even shares some tips for how to reduce anxiety during their EP visits.The 2nd and 3rd Segments involve Anna reading from The Heart of a Heart Warrior Volume Two: Endurance.  This is one of the newest books from Baby Hearts Press. This is the second in a 3-book series of essays and works of art by adults with congenital heart defects.In this podcast episode, Anna will read from the front matter of the book, including the Foreword, Preface, and Introduction.Baby Hearts Press is hosting a Book Study for those interested in meeting some of the contributors to ask questions, as well as an opportunity to share their own experiences related to the topics discussed in the book. The Book Study for Volume Two begins on Thursday, March 24th from 5-6 PM Central Daylight Savings Time and runs for 4 consecutive Thursdays. To get a ticket to attend for only $10 per session, visit https://www.babyheartspress.com.Support the showAnna's Buzzsprout Affiliate LinkBaby Blue Sound CollectiveSocial Media Pages:Apple PodcastsFacebookInstagramMeWeTwitterYouTubeWebsite

NEJM 1991;324:781-788Background A hallmark of post-myocardial infarction (MI) care in the 1980's was the monitoring and suppression of premature ventricular contractions (PVCs) via use of antiarrhythmic drugs. The practice was based on pathophysiologic rationale that PVC burden is a strong risk factor for sudden and non-sudden cardiac death following MI and thus, suppression must reduce death. PVC reduction was a seductive surrogate endpoint that was easy to measure and declare victory on, but it had never been tested in a proper RCT. The Cardiac Arrhythmia Suppression Trial (CAST) was sponsored by the National Heart, Lung and Blood Institute (NHLBI) and sought to test the hypothesis that suppression of asymptomatic or mildly symptomatic PVCs with antiarrhythmic therapy with encainide, flecainide, or moricizine after MI would reduce death due to arrhythmia.Patients Patients were eligible for enrollment 6 days to 2 years post MI with an average of ≥6 PVCs per hour on ambulatory monitoring of at least 18 hours duration, and no runs of VT of ≥15 beats at a rate of ≥120 bpm. An ejection fraction (EF) of ≤55% was required within 90 days of MI or ≤40% if recruited after 90 days. There was a run-in phase. Patients were only enrolled in the main trial if they had at least 80% suppression of PVCs and at least 90% suppression of runs of VT during an initial, open-label titration period. Initial open-label drug assignment was based, in part, on the EF. Flecainide was not given to patients with an EF of ≤30%. Moricizine was only used as a second line drug in patients with an EF of ≥30%.Baseline characteristics Baseline characteristics of the patients enrolled in the trial are not provided in the main manuscript and cannot be inferred from the results, tables or figures presented.Procedures Patients in whom arrhythmias were suppressed were randomly assigned to receive either the effective drug or its matching placebo. A detailed description of study procedures is not presented in the main manuscript. Compliance with the study drug was assessed in follow-up visits and based on pill counts of tablets returned but the schedule of these visits is not provided. Concomitant drug therapy was assessed at the time of the last visit, according to a standardized checklist.During the trial, patients could be instructed to discontinue the study drug based on the occurrence of the following events: ventricular tachycardia, significant increase in arrhythmia burden, disqualifying ECG changes including significant QT prolongation or bradycardia, new or worsened congestive heart failure, the need for treatment with an antiarrhythmic agent outside the entry criteria for the study, or any number of other adverse medical events divided into cardiovascular or non-cardiovascular events.Endpoints The primary endpoint of the study was death or cardiac arrest with resuscitation due to arrhythmia. The site PI was responsible for classifying each death without knowledge of the patient's assigned treatment. Secondary endpoints included cardiovascular and non-cardiovascular causes of death, disqualifying ventricular tachycardia without arrest, syncope, pacemaker implantation, recurrent MI, congestive heart failure, angina pectoris or coronary artery revascularization.Results Observation began on the day of randomization to blinded therapy and was censored on April 18, 1989, the date when the use of encainide and flecainide was discontinued by the Data and Safety Monitoring Board because the data indicated it was unlikely that benefit could be demonstrated, and it was likely that the drugs were harmful. The original CAST trial manuscript reports data on patients assigned to the encainide and flecainide groups. Moricizine use was continued and would be reported separately in the revised CAST II trial.1498 participants were randomized to receive either encainide, flecainide or their matching placebo and followed for an average of 10 months. Compliance with the assigned treatments was estimated to be >90% in 70% of all patients and was similar in the active-drug and placebo groups. Antiarrhythmic therapy significantly increased the relative risk of the primary endpoint of death or cardiac arrest due to arrhythmia (RR 2.64; 5.7% vs 2.2%; p=0.0004) and was associated with a number needed to harm (NNH) of approximately 29. It also increased the risk of all deaths and cardiac arrests (RR 2.38; 8.3% vs 3.5%; p=0.0001; NNH = 20); even those not associated with arrhythmia (2.3% vs 0.7%; p=0.01).Conclusions The CAST trial unexpectedly demonstrated that treatment of asymptomatic or mildly symptomatic PVCs in post-MI patients, with encainide and flecainide, increased death and cardiac arrests. From a chronological standpoint, it is the first major trial in cardiovascular medicine (perhaps all of medicine) that “reversed” a standard medical practice. In this case, one that was instituted and broadly adopted on the basis of pathophysiologic reasoning and one that targeted a surrogate endpoint. Thus, more than anything it highlights the importance of testing interventions in properly conducted RCTs prior to adoption and basing the analysis on hard outcomes that are meaningful to patients and society. How many practices in modern medicine are supported by high quality RCTs? It may be as low as 30-40%. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Listen in this episode of DC Power Hour as our battery Blarney duo of George and Allen field questions from Doug on our sales team. They discuss topics ranging from seismic racking to spill containment and neutralization to chargers.Episode Highlights:1:57 – What are the seismic and UBC zones and how have they changed over time?7:40 – If you put the spacers in, you've just got rid of half the airflow that's necessary to keep the battery cool.9:46 – What are the pros and cons of Stevrofoam sheets vs corrugated PVCs in regards to airflow for the racks?14:10 – Spill containment, is it recommended for VRLA purviews?19:35 – Does the spill containment count as a neutralization kit?

Jason T. Jacobson, MD, FHRS, of Westchester Med Center-New York Med College discusses A Novel ECG-Based Deep Learning Algorithm to Predict Cardiomyopathy in Patients With Premature Ventricular Complexes with Daniel Frenkel, MD, FHRS, of Westchester Medical Center, and Jagmeet P. Singh, MD, PhD, FHRS, of Massachusetts General Hospital. This study utilized a machine learning algoritihm to predict the devlopment of cardiomyopathy in patients with PVCs based on the baseline ECG.   https://www.hrsonline.org/education/TheLead https://www.jacc.org/doi/10.1016/j.jacep.2023.05.025   Host Disclosure(s): J. Jacobson: Honoraria/Speaking/Consulting Fee: American College of Cardiology, Zoll Medical Corporation; Research (Contracted Grants for PIs Named Investigators Only): Abbott, Phillips; Stocks (Privately Held): Atlas 5D   Contributor Disclosure(s): D. Frenkel: Ownership/Partnership/Principal: Summit Health J. Singh: Honoraria/Speaking/Consulting Fee: Medtronic, EBR Systems, Boston Scientific, Biotronik, Abbot, MicroPort Scientific Corporation, Cardiologs, Sanofi, CVRx Inc., Impulse Dynamics, USA, Implicity, Orchestra Biomed, Rhythm Management Group Corp, Medscape, Biosense Webster Inc., Notal Vision, iRhythm Technologies, Philips

Light Round Volume 5: Approach to a patient with frequent PVCs

Cardiologist explains PVCs and PACs and when you need to start worrying. https://dralo.net/links

FDA says Popular Decongestant is Ineffective and the Impact of Coffee on Arrhythmia Guest: Dr. Kavita Chawla, Chair - EBM Education Committee, Internal Medicine, Virginia Mason Franciscan HealthArticles referenced: https://www.nejm.org/doi/full/10.1056/NEJMoa2204737In this 5-minute check in, Dr. McGinn and guest Dr. Kavita Chawla review two health care topics making headlines: An F.D.A. panel says a common decongestant found in many over-the-counter cold medicines is ineffective. Dr. McGinn and Dr. Chawla discuss the findings and what this means for patients. The “CRAVE” trial (Coffee and Real-time Atrial and Ventricular Ectopy) published in the NEJM studies the short term impact of caffeine on palpitations in relatively healthy people. Dr. McGinn and Dr. Chawla review the impact of coffee on PACs, PVCs as well as on step counts and sleep.

The following question refers to Section 4.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.The question is asked by Texas Tech University medical student and CardioNerds Academy Intern Dr. Adriana Mares, answered first by Rochester General Hospital cardiology fellow and Director of CardioNerds Journal Club Dr. Devesh Rai, and then by expert faculty Dr. Eldrin Lewis.Dr. Lewis is an Advanced Heart Failure and Transplant Cardiologist, Professor of Medicine and Chief of the Division of Cardiovascular Medicine at Stanford University. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #26 A 45-year-old man presents to cardiology clinic to establish care. He has had several months of progressive dyspnea on exertion while playing basketball. He also reports intermittent palpitations for the last month. Two weeks ago, he passed out while playing and attributed this to exertion and dehydration. He denies smoking and alcohol intake.   Family history is significant for sudden cardiac death in his father at the age of 50 years. Autopsy has shown a thick heart, but he is unaware of the exact diagnosis. He has two children, ages 12 and 15 years old, who are healthy.   Vitals signs are blood pressure of 124/84 mmHg, heart rate of 70 bpm, and normal respiratory rate. On auscultation, a systolic murmur is present at the left lower sternal border. A 12-lead ECG showed normal sinus rhythm with signs of LVH and associated repolarization abnormalities. Echocardiography reveals normal LV chamber volume, preserved LVEF, asymmetric septal hypertrophy with wall thickness up to 16mm, systolic anterior motion of the anterior mitral valve leaflet with 2+ eccentric posteriorly directed MR, and resting LVOT gradient of 30mmHg which increases to 60mmHg on Valsalva.   You discuss your concern for an inherited cardiomyopathy, namely hypertrophic cardiomyopathy. In addition to medical management of his symptoms and referral to electrophysiology for ICD evaluation, which of the following is appropriate at this time? A  Order blood work for genetic testing B  Referral for genetic counseling C  Cardiac MRI D  Coronary angiogram E  All of the above Answer #26 Explanation   The correct answer is B – referral for genetic counseling.  Several factors on clinical evaluation may indicate a possible underlying genetic cardiomyopathy. Clues may be found in: ·       Cardiac morphology – marked LV hypertrophy, LV noncompaction, RV thinning or fatty replacement on imaging or biopsy ·       12-lead ECG – abnormal high or low voltage or conduction, and repolarization, altered RV forces ·       Presence of arrhythmias – frequent NSVT or very frequent PVCs, sustained VT or VF, early onset AF, early onset conduction disease ·       Extracardiac features – skeletal myopathy, neuropathy, cutaneous stigmata, and other possible manifestations of specific syndromes In select patients with nonischemic cardiomyopathy, referral for genetic counseling and testing is reasonable to identify conditions that could guide treatment for patients and family members (Class 2a, LOE B-NR). In first-degree relatives of selected patients with genetic or inherited cardiomyopathies, genetic screening and counseling are recommended to ...

In this episode, I talk about Cardiophobia aka the fear of your heart-related symptoms (heart palpitations, PVCs, skipped heartbeats, heart flutters, chest tightness, etc). I explain exactly what this is and what it can look like for people who are struggling with this fear. I also share many tips and strategies on how to start responding differently to your symptoms in order to get relief from them so that you can ultimately recover from Cardiophobia. You are not alone if this is something you experience! FREE GUIDE - The Ultimate Health Anxiety Toolkit https://haley-joy.ck.page/c0e33657db MASTERCLASS - Heal Your Health Anxiety ⁠⁠⁠⁠⁠ ⁠⁠https://haley-joy.mykajabi.com/offers/CTFDkAJv⁠⁠ SCHEDULE THERAPY with me: PA, NJ, and FL residents only https://www.innergrowthcounseling.com INSTAGRAM: https://www.instagram.com/your.anxious.therapist/ TIKTOK: https://www.tiktok.com/@youranxioustherapist/ --- Send in a voice message: https://podcasters.spotify.com/pod/show/haley-ostrow/message

In this episode of Kubernetes Bytes, Ryan and Bhavin sit down with Sachin Mullick and Peter Lauterbach - the Product Management team at Red Hat focused on Red Hat OpenShift Virtualization and the open-source KubeVirt project and talk about how users can run containers and virtual machines side-by-side on the same Kubernetes cluster. They discuss the benefits of having a unified control plane for all your applications and the different features that enable users to run their applications in production. They also talk about some customers that have implemented this technology in production. Listen to learn more about how you can get started with KubeVirt and run your VMs alongside your Kubernetes pods on your Kubernetes or OpenShift clusters. 03:27 - News Segment 13:54 - KubeVirt Interview 01:06:12 - TakeawaysThe Motley Fool: Save $110 off the full list price of Stock Advisor for your first year, go to http://www.fool.com/kubernetesbytes and start your investing journey today! *$110 discount off of $199 per year list price. Membership will renew annually at the then current list pricShow Notes: 1. Kube by Example - https://kubebyexample.com/ 2. Ask An OpenShift Admin - https://youtube.com/playlist?list=PLaR6Rq6Z4IqdsG6b09q4QIv_Yq5fNL7zh 3. https://kubevirt.io/ 4. https://www.redhat.com/en/technologies/cloud-computing/openshift/virtualization Cloud-Native News: 1. New Security Startup - Stacklok - https://techcrunch.com/2023/05/17/kubernetes-and-sigstore-founders-raise-17-5m-to-launch-software-supply-chain-startup-stacklok/ 2. Traefik Lab announces Traefik Hub - Also raised $11M https://techcrunch.com/2023/05/17/traefik-labs-launches-traefik-hub-a-kubernetes-native-api-management-service/ 3. KSOC releases the KBOM standard - https://tech.einnews.com/pr_news/629861155/ksoc-releases-the-first-kubernetes-bill-of-materials-kbom-standard 4. Upbound announces managed Crossplane service - https://www.infoq.com/news/2023/05/upbound-managed-control-plane/ 5. Kubernetes 1.27 StatefulSet auto deletion for PVCs to beta https://kubernetes.io/blog/2023/05/04/kubernetes-1-27-statefulset-pvc-auto-deletion-beta/ 6. Cost reduction CAST AI company focuses on reducing compute costs running generative AI models on k8s https://siliconangle.com/2023/05/18/kubernetes-firm-cast-ai-adds-support-reducing-generative-ai-deployment-costs/ 7. Vault secret store operator https://thenewstack.io/hashicorp-vault-operator-manages-kubernetes-secrets/ 8. Managed Kafka or Run it yourself ? https://thenewstack.io/kafka-on-kubernetes-should-you-adopt-a-managed-solution/ 9. Cool usecase - edge k8s - robots picking fruit - https://thenewstack.io/fruit-picking-robots-powered-by-kubernetes-on-the-edge/ 10. Knative 1.10 release https://knative.dev/blog/releases/announcing-knative-v1-10-release/ (4-25 missed it)

Welcome to another exciting podcast episode, where we dive into the latest cardiovascular research! Join us as we discuss four fascinating studies: STUDY #1: Discover how subclinical coronary atherosclerosis detected by computed tomographic angiography (CTA) can pose a significant risk for myocardial infarction (MI) in asymptomatic middle-aged men and women in a Danish cohort. Fuchs A et al. Subclinical coronary atherosclerosis and risk for myocardial infarction in a Danish cohort: A prospective observational cohort study. Ann Intern Med 2023 Mar 28; [e-pub]. (https://doi.org/10.7326/M22-3027) STUDY #2: We'll examine the Open Payments Program (OPP) data, revealing trends in industry payments to cardiologists from 2014 to 2019, including the necessity for transparency. Zhang R et al. Trends in industry payments to cardiologists from 2014 to 2019. Circ Cardiovasc Qual Outcomes 2023 Mar 17; [e-pub]. (https://doi.org/10.1161/CIRCOUTCOMES.122.009820) STUDY #3: In this randomized case-crossover study, we'll explore whether caffeinated coffee affects premature atrial contractions (PACs) and ventricular contractions (PVCs) in healthy adults. Marcus GM et al. Acute effects of coffee consumption on health among ambulatory adults. N Engl J Med 2023 Mar 23; 388:1092. (https://doi.org/10.1056/NEJMoa2204737) STUDY #4: Lastly, we'll discuss a phase 3 trial of sotatercept, a potential new class of therapy for pulmonary arterial hypertension (PAH), focusing on its effects on 6-minute walk distance and other secondary endpoints. Hoeper MM et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med 2023 Mar 6; [e-pub]. (https://doi.org/10.1056/NEJMoa2213558) This episode promises to be a wealth of knowledge and insights into cardiovascular health. So, get comfortable, grab your headphones, and let's dive into these captivating studies to uncover the secrets to a healthier heart. Enhance your understanding and make a difference in patients' lives. See you there! For shownotes, visit us at https://www.medmastery.com/podcasts/cardiology-podcast.  

The much anticipated presidential election in Nigeria on 25th Feb was competitive, controversial and climactic. In this episode, Evelyn and Lara shared their observations of the day, expectations for Peter Obi and Nigerian youths as they prepare for another 8 years of APC government under the leadership of President Bola Ahmed Tinubu. This is our final episode for this season. We have thoroughly enjoyed being on this road to the 2023 presidential election with our listeners and we look forward to returning with another engaging season in July. Until then, feel free to listen to all our past episodes, share and engage with us on all our social media platforms. By the way, you may notice that our description of the BVAS was not totally coherent in this episode so before you flog us, here is our correction. "The Bimodal Voter Accreditation System (BVAS), is a device introduced by INEC in 2021 aimed at stopping election fraud. The BVAS is essentially a small rectangular box with a screen that is more technologically advanced than the Smart Card Readers used in the past. The key benefit of the BVAS is that it has the capacity to perform dual identification of voters on election day through their fingerprints and facial recognition. This should stop people without valid PVCs from voting, as well as those who are ineligible to vote attempting to do so. Another aspect of the BVAS is that it uploads (supposedly) vote results directly to the Inec results portal for all to see, which in theory means results cannot be tampered with". Be sure to check us out on Spotify, YouTube, Apple podcasts and wherever you get your podcast. Follow us on Instagram @onceuponanaija. Would you like to collaborate with us or just send some encouragement? Email us at onceuponanaija@gmail.com. You can find links to some further reading and information about this episode's topic in the show notes: https://www.stears.co/premium/article/why-was-voter-turnout-in-the-2023-general-elections-so-low/ https://republic.com.ng/february-march-2023/2023-election-updates/ https://republic.com.ng/february-march-2023/youth-participation-nigeria-elections/ www.google.com/amp/s/www.bbc.com/news/world-africa-64187170.amp

A large number of people are not happy, and others are happy with the turnout of the just concluded elections. What lessons can we derive from the elections, and how can we use them to improve the forthcoming governorship and House of Assembly elections coming up? What are the mistakes that were made and that need to be corrected? How do we move forward starting now? We were all Nigerians first before tribe, so as a nation, we must remain one. A total of 93 million people registered to get their PVCs, and 87 million of them were collected; this goes on to show that we made a statement, but it's not just about making statements; it's about exercising your civic rights and responsibilities, which can only be achieved by going out to vote. On today's episode of Signals, our host interacted with the listeners, asking them about their expectations for the forthcoming governorship and House of Representative's elections. A lot of callers called in and gave their opinions; some voiced their grievances about the past election and hoped that INEC would use this governorship election to redeem its image. Listen here……..

Nigeria elections is today!

Visit Harvest Eating Now! When it comes to electrolytes I did not know very much until about 8 mos ago. You'd think with my athletic background which spanned the gamut from decades of ice hockey at a serious level, tennis, mountain biking, and even mountain bike racing that I would be familiar with electrolytes, but no. Aside from Gatorade which I hate, I really was not aware that average people, or anyone not a paid athlete, can benefit from electrolyte consumption. I followed the “health experts” who said to drink 8 glasses of water each day, more if you're sweating, but they were always demonizing salts in every form. Remember a low-sodium, low-fat, and plant-based diet is best…! We've all heard this nonsense from the FDA on sodium intake, I think it's crap. I even listened to my own doctors who pretty much caused an electrolyte deficiency by prescribing medications that cause fluid and mineral loss and then double-downed with advice to take other prescriptions to help with symptoms caused by the prior medicines, read-lunacy! A few years back during a routine checkup my by was a touch high, 125/80 and the doctor advised going on a low dose BP med basically so my wife would not worry. I also had started snoring for the first time, so the doctor and my wife were worried about potential sleep apnea and future heart problems so I agreed on the low dose of BP meds. A few years later, I started having some weird heart rhythm issues called PVCs which are common, about 20 million Americans have this. It's not life-threatening but it can be very strange and uncomfortable when your heart flops around. I was referred to a cardiologist and prescribed yet another drug. Still blindly following the advice I started that medication, but after a few weeks I hate the side effects and threw it away, and never went back to the cardiologist. The PVCs continued for years and were ok sometimes but not always. I started exercising more and realized I could not be on meds that caused excessive urination, because with additional sweating I would get dizzy, likely from dehydration and electrolyte imbalances so I had the meds changed and decided to see a functional medicine practitioner instead of the family MD who just followed his guidelines and gave the same dumb advice. During this process, the functional medicine doctor had extensive blood panels drawn, like 12 vials of blood. They tried to take blood in the office, but the physician's assistant got no blood from the left arm, she switched to the right and go no blood, that's how dehydrated I was. She had never seen this in any patient. I waited for a few days and drank a ton of water and went again, this time some blood came out, but still not flowing that freely. The results showed my electrolytes were way out of balance with potassium and sodium low, and magnesium slightly low. They suggested I take some electrolytes and after doing some research I settled on one. Within a week the constant PVCs went away, and except for a 2-day period, they have been gone which is amazing. My BP is quite a bit lower and I know am only on half the prescribed dose and working to shed the last 15 pounds I have to lose to get to my goal of 155 pounds and hopefully be off all meds! I am riding my bike a lot more and really seeing great health improvements and I credit electrolytes with much of that improvement, especially with increased energy. Important Links: Support Harvest Eating Join Food Storage Feast Brown Duck Coffee About Chef Keith Snow Some of My Fav Recipes   Resources for today's Show: https://drinklmnt.com/pages/our-story https://myoxcience.com/collections/hormone-adrenal-support  

From Chest Pain to Myocardial Bridge Diagnosis and Surgery at Stanford, Jeff Holden recounts a life-changing episode that shifted his perspective on health, empathy, and purpose. An avid cyclist, Jeff was blindsided by a severe medical emergency that defied his otherwise stellar physical condition. This episode dives into the mystery of his heart condition, the surreal experiences during his recovery, and the transformative moments that followed. Plus, discover how Jeff's journey led him to launch a new podcast aimed at helping others dealing with similar health issues. Show notes:0:00 Introduction1:40 "What gets you up in the morning?"2:05 Jeff dives into his story starting with the Death Ride in July 20213:30 By August, he was experiencing a deep burning in his chest5:00 Sees his primary physician who recommends he sees his cardiologist6:00 By that Thursday, he woke at 5:45am with all the sensations of a heart attack, 911 is called and the EMTs find a heart attack and he's wheeled out of his house to the ambulance with a pulse of 468:00 Jeff has a catherization and nothing is found9:20 He starts cardiac rehab and was experiencing PVCs which became problematic in addition to vasospasms10:10 Jeff tries multiple medications11:00 Last day of cardiac rehab September 2021 where he had "the sensation" after climbing stairs in the garage11:50 The cardiologist calls and calls Jeff to the hospital as he had just had ventricular tachycardia episode. As in RIGHT NOW. His spasm episodes were triggering the tachycardia.13:45 Electrophysiologist casually mentions Jeff has a myocardial bridge but that it is benign but Jeff pushes back14:30 Jeff asks for a bypass of the LAD that is bridged but the doctor says, "we don't do that"15:00 Jeff's cardiologist says "it's beyond us" and recommends provocative testing15:30 Stanford is recommended and he sees Dr. Tremmel16:30 Jeff learns his myocardial bridge is 40mm long and when he is experiencing vasospasms in the LAD, it is 98% blocked17:20 Jeff had unroofing surgery at Stanford January 4, 202217:50 prior to surgery, Jeff quizzes Dr. Jack Boyd on his success rate which is great coaching for listeners. Take note!18:45 Boots recommends the Myocardial Bridge Facebook group which is a treasure trove of information20:10 Jeff feels much improvement since his unroofing21:10 Jeff connects with a marathon runner who also had unroofing in August 2021 and is doing well too22:00 Jeff and Boots met through the Facebook group thankfully.22:30 Jeff revisits why he gets up in the morning23:00 how we have to be our own best advocate.23:30 Jeff shares what he did to recover in addition to prepping for surgery including having the pre-surgery to surgery which is semi-comical.25:30 Jeff felt the power of prayer27:00 recovery was a little rough. He did not "dig" ICU at all. Sleep deprivation was an issue.28:00 Jeff takes control of his recovery.28:40 Boots shares her ICU story with Jeff.29:20 Jeff is sent home and his wife promptly gets sick. He even empties the dish washer.30:00 Minor blip and Jeff has to go to the ER and then comes down with Covid!31:00 Jeff and Boots reminisce about the heart pillow31:30 Boots asks Jeff what surprised him the most about open-heart surgery32:20 Boots asks what has been most helpful?33:10 Jeff laments how his wife was impacted34:30 Grace, gratitude, appreciation for the medical community34:50 He never felt sorry for himself. He just asked a lot of questions and did what he had to do to survive.36:00 He believes there is a reason why all of this happened the way it happened.37:00 Jeff shares about an important dream.39:10 Jeff asks Boots if she had an important dream, and she shares the impact on...

In this episode, Akindare and Jemima discuss Nigeria's leading presidential candidates', elections in Nigeria and why its important for us all to engage with politics on some level. Nigerians, please get their PVCs. What are your thoughts & experiences in the run-up to Nigeria's 2023 elections? Share with us on Twitter: @theshrinepod; Instagram: @theshrine.pod, or by email at theshrinepodcast@gmail.com. Join The Shrine on Clubhouse and become a member of our community. Everyone is welcome! 

Babak Nazer, MD directs the UW Translational Electrophysiology Laboratory, where his research focuses on the diagnosis and treatment of ventricular arrhythmias (premature ventricular complexes (PVCs) and ventricular tachycardia (VT). In collaboration with acoustic physicists and biomedical engineers, his laboratory develops new diagnostic and therapeutic ablation tools for the treatment of PVCs and VT, particularly those using ultrasound as an energy source.  As Director of the UW Multidisciplinary Ventricular Arrhythmia Program, he collaborates with psychologists to investigate the psychosocial symptoms associated with VT and defibrillator shocks, and therapies to alleviate these symptoms. bnazer@uw.edu

The following question refers to Section 7.4 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by New York Medical College medical student and CardioNerds Intern Akiva Rosenzveig, answered first by Cornell cardiology fellow and CardioNerds Ambassador Dr. Jaya Kanduri, and then by expert faculty Dr. Randall Starling.Dr. Starling is Professor of Medicine and an advanced heart failure and transplant cardiologist at the Cleveland Clinic where he was formerly the Section Head of Heart Failure, Vice Chairman of Cardiovascular Medicine, and member of the Cleveland Clinic Board of Governors. Dr. Starling is also Past President of the Heart Failure Society of America in 2018-2019. Dr. Staring was among the earliest CardioNerds faculty guests and has since been a valuable source of mentorship and inspiration. Dr. Starling's sponsorship and support was instrumental in the origins of the CardioNerds Clinical Trials Program.The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #6 Mr. D is a 50-year-old man who presented two months ago with palpations and new onset bilateral lower extremity swelling. Review of systems was negative for prior syncope. On transthoracic echocardiogram, he had an LVEF of 40% with moderate RV dilation and dysfunction. EKG showed inverted T-waves and low-amplitude signals just after the QRS in leads V1-V3. Ambulatory monitor revealed several episodes non-sustained ventricular tachycardia with a LBBB morphology. He was initiated on GDMT and underwent genetic testing that revealed 2 desmosomal gene variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). Is the following statement true or false? “ICD implantation is inappropriate at this time because his LVEF is >35%” True   False   Answer #6 Explanation This statement is False. ICD implantation is reasonable to decrease sudden death in patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death who have an LVEF ≤45% (Class 2a, LOE B-NR). While the HF guidelines do not define high-risk features of sudden death, the 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy identify major and minor risk factors for ventricular arrhythmias as follows: Major criteria: NSVT, inducibility of VT during EPS, LVEF ≤ 49%. Minor criteria: male sex, >1000 premature ventricular contractions (PVCs)/24 hours, RV dysfunction, proband status, 2 or more desmosomal variants. According to the HRS statement, high risk is defined as having either three major, two major and two minor, or one major and four minor risk factors for a class 2a recommendation for primary prevention ICD in this population (LOE B-NR). Based on these criteria, our patient has 2 major risk factors (NSVT & LVEF ≤ 49%), and 3 minor risk factors (male sex, RV dysfunction, and 2 desmosomal variants) for ventricular arrhythmias. Therefore, ICD implantation for primary prevention of sudden cardiac death is reasonable. Decisions around ICD implantation for primary prevention remain challenging and depend on estimated risk for SCD, co-morbidities, and patient preferences, and so should be guided by shared decision making weighing the possible benefits against the risks,

The captain's mind remains a beautiful enigma with its ability to connect the most random of thoughts to paint a picture what framing. Talking on a thousand ways to die, healthy cultism and Orijin Bitters to emphasize the importance of time (management), Cavey charges listeners to be always with deliberate. ps: Nigerians in Nigeria, have you picked up your PVCs? --- Send in a voice message: https://anchor.fm/naked--baked/message

On today's episode, our host Adewunmi Oshodi engaged our listeners on PVCs collection. She wanted to know if the listeners had collected their PVCs or not. For those that were yet to collect their PVCs, she wanted to know what was stopping them. She mentioned that some people that are yet to get their PVCs felt it was a deliberate attempt by INEC officials not to allow them to vote. Citing that people could volunteer themselves to make the process easier and faster. The listeners had an opportunity to call in and share their views and experience in collecting their PVCs.  Most of the callers had a lot to share, and some praised INEC for an easy collection, while some faulted INEC due to the stress they had to go through to get their PVC. In conclusion, the host wanted to know what happens to uncollected PVCs and encouraged everyone to go to the center they registered in, or go to their ward, if their center could not provide it. Listen here…………  

The Independent National Electoral Commission has again commenced the distribution of Permanent Voters' Cards to registrants at the 8,809 electoral wards across Nigeria. INEC National Commissioner, Festus Okoye says the devolution of PVC collection to the wards commences tomorrow 6th January 2023, and all validly registered voters who are yet to collect their PVCs are encouraged to seize the opportunity of the devolution to the wards to do so. Okoye says all those who applied for the replacement of lost, damaged, or defaced PVCs can collect their PVCs at the wards during the same period. He noted that the PVCs of those that applied for transfer are available for collection in the local governments and registration areas where they intend to vote and not in the state or local government where they carried out the transfer.

PVCs: 6.7 million uncollected in 17 states, INEC targets markets. --- Send in a voice message: https://anchor.fm/jay-fm-podcast/message

It's 64 days to the 2023 general elections, and the Independent National Electoral Commission, INEC, has started distribution of the permanent voter's cards.How many Nigerians have collected theirs?In this episode of Nigeria Daily, we look at how Nigerians are headstrong in collecting their PVCs despite all odds.

#AduandTheGuru Discussing the following stories in the news; 1. Senators, Reps face probe over illegal budget passage – Punch 2. Naira in another record fall as CBN moves to replace naira notes – Premium Times 3. We knew nothing about naira redesign, says Finance Minister – The Nation 4. Return of queues: How operators, smugglers steal N200.8b monthly in petrol subsidy claims – Guardian Newspaper 5. Police nab man with 101 PVCs in Sokoto – Vanguard

Twenty-four Nigerians have filed a lawsuit against the Independent National Electoral Commission for failing to give them and the other seven million Nigerians adequate time and opportunity to complete their voter registration after they have carried out their registration online. The Plaintiffs are seeking an order of mandamus to direct and compel INEC to re-activate its continuous voter's registration exercise to allow the Plaintiffs to complete their registration and collect their Permanent Voters' Cards. The Plaintiffs are also seeking an order of mandamus to direct and compel INEC to provide adequate facilities and deploy personnel to the registration units of the Plaintiffs to enable them complete their registration and collect their PVCs.

A smart speaker and your Heart. “ Alexa, is my heart rhythm normal”? An Electro Cardiologist interfaces a clinical problem with a smart speaker to identify cardiac arrhythmias. Learn how innovation in biotechnology had led a cardiologist and his team to train Alexa to determine abnormal from normal heart rhythms. Still in development, this fascinating interface highlights how leading innovators take technology and smart devices forward to enhance clinical care.  Listen as we review common cardiac arrhythmias, causes, treatments and diagnosis current and future. Directions for innovation with devices and additional developments in Telehealth.   Guest:  Arun Mahankali Sridhar, M.D., M.P.H., is a cardiac electrophysiologist and a specialist in heart rhythm disorders. He is an Assistant Professor in the Division of Cardiology at the University of Washington.  Dr. Sridhar's sees patients with both rapid and slow heart rhythm disorders, as well as patients with a risk of sudden cardiac death. He has comprehensive expertise in management of both common and complicated arrhythmias. He is an expert in catheter ablations for atrial fibrillation; atrial flutters (both typical and complex), supraventricular tachycardia, WPW, ventricular tachycardia (VT) and premature ventricular complexes (PVCs); stroke prevention in atrial fibrillation, including left atrial appendage closure; In addition he is an experienced implanter of all types of cardiac device therapy, including cardiac pacemakers; implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy (CRT).  Dr. Sridhar's research focuses on improving ablation techniques and patient outcomes in atrial arrhythmias. He collaborates with the UW computer science and bio-engineering department on various innovation projects to improve the care of heart rhythm patients utilizing advanced computing and novel low-cost patient accessible technologies.     During This Episode We Discuss:  Cardiac (Heart) Arrhythmias: causes, detection and treatment options.  Innovations in the diagnosis of arrhythmias.  The benefits of a multi disciplinary team in researching a very innovative solution to a common clinical problem.  The role of adaptive, machine learning, signal processing and clinical experience in moving technology forward.  Future potential enhancements in current technology to diagnose other metabolic, cardiac and respiratory conditions.    Recommended Resources:  Nature: COMMUNICATIONS BIOLOGY| (2021) 4:319 | https://doi.org/10.1038/s42003-021-01824- https://www.nature.com/articles/s42003-021-01824-9.pdf  UW Cardiology website  Stopafib.org      Visit our website for all the podcasts, additional resources and social media links Website: theoriginalguidetomenshealth.org Facebook: https://www.facebook.com/theoriginalguidetomenshealth/ Twitter: https://twitter.com/guide2menshlth Linkedin: https://www.linkedin.com/company/the-original-guide-to-mens-health/  

Quote of The Day: "You don't need people to validate your gift; you were gifted before they met you". ~ Bishop T.D Jakes Hosts: TOLA Omoniyi, Olufunke Aderogba, Eyiyemi Olivia

For more information on this topic or to schedule a consultation please visit us at http://WhatIsHashimotos.com We're going to talk about Hashimoto's and heart problems. This is kind of an interesting one. And I'm going to speak to you strictly from experience on this because a lot of people are looking for, “Oh, it's causing this exact thing, that to the heart and it's creating the bundle branch to not work right,” and blah, blah, blah, and all that type of stuff. But I'm going to tell you the nuts and bolts, blue collar aspect of Hashimoto as a heart disease. So I've been doing this for a long time, seen thousands and thousands and thousands and thousands of patients. And here's what I hear. I am going to grew greatly downplay how many times I think I've heard this, but I have heard this somewhere between 500,000 times. And I think probably more, but this is how common it is. The patient comes in and maybe they don't even know that they have autoimmune disease at that time, maybe they don't even know that they got a thyroid problem at that time. And so you're sitting there are listening and digging and taking notes and trying to go, “Okay, what's going on here? Does this person fit my practice? Do they have autoimmune problems?” And then it happens. Then I ask, “Do you have heart palpitations for no reason at all? Heart palpitations or anxiety for no reason at all? Would you call that PVCs, pre ventricular contractions? Would you call that SVPs?” These are all medical pathology that cause your heart to beat out of your chest. And then I'm like, “Well, tell me more about that.” Here's the story. “I was under a lot of stress and then all of a sudden, for no reason at all, for no reason at all, my heart started to really pound. And I really started to get big time arrhythmias. And I couldn't breathe very well, and I was really getting anxiety and so on and so forth. [inaudible 00:02:05]. So I was at a hospital and then they did an EKG, they did an echogram, they did a cardiogram, they did everything. And everything was normal,” for the lucky ones. For the lucky ones. “And everything was normal. And they told me to go home and they told me to take some electrolytes and I'm probably just stressed and maybe I just need to deal with my stress and go to counseling. ‘But if it happens again, maybe you can go to cardiologist,' even though everything was normal.” The second person, who's not always quite as fortunate, they'll pick something up on some of the electrical diagnostics and they'll go, “Okay, we're going to go in and we're going to ablate the nerves that are causing your heart to do that…” And then they do that. But the patient's still sitting in front of me with heart palpitations for no reason at all, and anxiety for no reason at all, and those types of things, even though they've been ablated. So when I see questions that come in on does Hashimoto's cause heart problems, technically the answer is no. However, not technically, the answer is yes. And here's how it happens. http://powerhealthtalk.com http://drmartinrutherford.com Martin P. Rutherford, DC 1175 Harvard Way Reno, NV 89502 775 329-4402 http://powerhealthreno.com https://goo.gl/maps/P73T34mNB4xcZXXBA

In this episode, we discuss PVCs, live shows, first jobs, work experiences, tiring jobs working in Nigeria and abroad and career lessons so far. Make sure you like, share and rate us everywhere you listen to podcasts. Twitter – @Roadto30podcast, @IsaacKanye_, @Dolly.writes Instagram – @Roadto30podcast, @IsaacKanye_, @DollyAkitoye,

Trade – OsmitrolClass – Osmotic DiureticMOA – Facilitates the flow of fluid out of tissues including the brain and into interstitial fluid and blood, this causes dehydration of the brain which results in decreased swelling. Reabsorption by the kidneys is limited so increased urine output takes placeIndications – increased ICPContraindications- Active intracranial bleeding, heart failure, pulmonary edema, severe dehydration, use caution with hypovolemia and renal failure.Side effects – Pulmonary edema, headache, blurred vision, dizziness, seizures, hypovolemia, nausea/vomiting, diarrhea, electrolyte imbalance, hypotension/HTN, sinus tachycardia, PVCs, angina, phlebitis DosageAdult: 0.25-1g/kgPediatric: SAA

https://go.dok.community/slack https://dok.community/ From the DoK Day EU 2022 (https://youtu.be/Xi-h4XNd5tE) Multiple clusters exist in most Kubernetes environments today, and number of clusters will increase overtime. The reasons for having multiple Kubernetes clusters are many, for example, overcoming scale limits, reducing complexity, geo separation, redundancy and having separate production, staging, and development environments. Once you have multiple K8S clusters, it can be useful to have the ability to easily move or duplicate workloads across these different clusters. Kubernetes does not have a native method to allow migration or duplication of workloads across clusters. Fortunately, there are tools that provide this functionality. In this presentation we will explore the different uses cases for cross cluster migration, and what is involved, and how these migration tools work. We'll cover some popular uses cases, such as, Disaster Recovery, Test/Dev, and performance testing. Migration could entail moving the entire cluster, or individual workloads. The components that need to be moved would include configuration and resources stored in etcd, and persistent data residing on PVCs. We'll cover the uses cases and challenges for migration, and run through an example of using one of these migration tools.

https://go.dok.community/slack https://dok.community/ From the DoK Day EU 2022 (https://youtu.be/Xi-h4XNd5tE) Accidental PVC delete or namespace delete can cause the Persistent Volume to get deleted. Such volumes lose their data and the stateful applications lose their state. By the use of Persistent Volume TrashCan, users can get a grace period to undo such unintended delete operation. The deleted Persistent Volumes are staged for delayed deletes. They continue to live even after being deleted from k8 perspective, for a configurable time(retention period) and based on the system's usage. The storage class of the PVC can dictate if they need to be staged for a delayed delete. StorageClass can also allow for configurable retention period. To recover a deleted PersistentVolume, users can create a new namespace with the same name and reapply the original PVC spec. The PVC will reference a special StorageClass to indicate that the new PersistentVolume needs to be restored from the TrashCan. This will allow the application to restart with the right state and data. This talk will showcase how to overcome one of the admin's pain point seen in field involving accidental deletions of PVCs by using advanced storage management solutions in Kubernetes. Veda Talakad is a Software professional with BS in electronics and communications mostly working in storage domain. Some of the professional areas of interests include scalability in distributed environment and cloud-native technologies for data management, Aditya Kulkarni: I have 10 years of experiance in Enterprise Data management. I have worked on All Flash Array at Netapp from the device driver layer to WAFL Filesystem. Next, I worked at Portworx where I developed and enhanced the number one data platform for Kubernetes. Then I moved to Pure Storage as part of Portworx acquisition. Aditya Dani is an architect at Portworx by PureStorage, that enables users to run any cloud-native data service, in any cloud, using any Kubernetes platform. He is one of the contributors to the open source project Stork that provides storage awareness to the Kubernetes scheduler. Prior to Portworx, Aditya worked for Amazon on their Music Recommendations Engine. He enjoys working on distributed systems and loves programming in Go.

• 00:13 - Ukraine / Russia war brief  • 00:14 - Why our parents were/are always tired. Hectic weekend for Sanmi  • 00:22 - Ladies, would you think your man wasn't man enough if you're getting disrespected and he doesn't step in?  • 00:34 - What is the single most expensive item that is not furniture or appliance in your home? • 00:37 - What is the thing you have the most of in your home? (It can't be food)  • 00:40 - Tragic state of Ukraine

Season 2 starts explosively! Lola OJ & Mandy are joined by a special guest, outspoken Falz aka Folarin Falana, they discuss a topic that gets constant airtime here, politics. Nothing is held back in this episode, they discuss the importance of the #EndSars movement, the up and coming elections, and why we should all have our PVCs. With the right balance of seriousness and banter, it's an episode you don't want to miss! Make sure you rate, share and leave a comment wherever you listen to the podcast telling us how much you enjoyed the episode!. Always use the hashtag LegalAvenuePodcast to let us know what you think of the episode, we love hearing from you... Follow Us on Social Media Instagram @legalavenuepodcast @mandyuzoagba @lolaoj Twitter @legalavenue_pod @mandyuzoagba @lola_oj --- Send in a voice message: https://anchor.fm/legal-avenue-podcast/message

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Loie Farina (Northwestern University CardioNerds Ambassador), Dr. Josh Cheema, and Dr. Graham Peigh from Northwestern University for drinks along the shores of Lake Michigan at North Avenue Beach. They discuss a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presents with progressive symptoms of heart failure and is found to have a severe, non-ischemic cardiomyopathy. The etiology of her cardiomyopathy is not clear until her untimely death. She is ultimately diagnosed with cardiac AL amyloidosis with isolated vascular involvement a real occam's razor or hickam's dictum conundrum. We discuss the work-up and management of her condition including a detailed discussion of the differential diagnosis, the underlying features of systemic sclerosis with cardiac involvement as well as cardiac amyloidosis, the role of a shock team in managing cardiogenic shock, and how to identify those with advanced or stage D heart failure. Advanced heart failure expert Dr. Yasmin Raza (Northwestern University) provides the ECPR segment.  Episode introduction by CardioNerds Clinical Trialist Dr. Liane Arcinas. Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls - Notes - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Summary - Occam's Razor or Hickam's Dictum? This is a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presented with progressive dyspnea on exertion and weight loss over the course of 1 year. Her initial work-up was notable for abnormal PFTs and finding of interstitial pneumonia on high-resolution CT, an ECG with frequent PVCs and normal voltage, a transthoracic echocardiogram with a mildly reduced ejection fraction of 40%, and a right/left heart catheterization with normal coronary arteries, filling pressures, and cardiac output. Scleroderma-related cardiac involvement is suspected. She is placed on GDMT, but her condition worsens over the next several months, and repeat echocardiogram shows severely reduced biventricular function, reduced LV global longitudinal strain (GLS) with apical preservation of strain, severely reduced mitral annular tissue Doppler velocities, and a normal left ventricular wall thickness. Scleroderma-related cardiac involvement remains highest on the differential, but because of some findings on the echo that are concerning for cardiac amyloidosis, an endomyocardial biopsy was obtained. It showed vascular amyloid deposition without interstitial involvement. The diagnosis of cardiac amyloid was discussed but deemed unlikely due to lack of interstitial involvement. However, a serologic work-up soon revealed a monoclonal serum lambda light chain and a follow-up bone marrow biopsy showed 20% plasma cells. She was discharged with very near-term follow-up in oncology clinic with a presumptive diagnosis of AL amyloidosis, but she unfortunately returned in shock and suffered a cardiac arrest. She initially survived and underwent emergent veno-arterial extracorporeal membrane oxygenation (VA ECMO) cannulation with subsequent left ventricular assist device placement (LVAD). However, she passed away due to post-operative hemorrhage. Autopsy was consistent with a final diagnosis of cardiac AL amyloidosis with isolated vascular involvement.  Case Media - Occam's Razor or Hickam's Dictum? EKG CXR TTE Pathology CMR Episode Teaching -Occam's Razor or Hickam's Dictum? Pearls Scleroderma causes repeated focal ischemia-reperfusion injuries which result in patchy myocardial fibrosis. Cardiac involvement in scleroderma is frequent but often not clinically evident; when symptomatic, it is associated with a poor prognosis.

We have a long-time friend of the pod on this episode and we discuss stolen milk, breakups, PVCs, savings accounts, and boundaries. How do you communicate your boundaries? What are your boundaries in relationships, at the workplace, with your family and friends? How do you handle other people's boundaries? Make sure you like, share and rate us everywhere you listen to podcasts. Link for the gage award nominations: https://gageawards.com/nominate Use the hashtag #Roadto30podcast to join in the conversation. Twitter – @Roadto30podcast, @IsaacKanye_, @DollyAkitoye, @yakub__m Instagram – @Roadto30podcast, @IsaacKanye_, @Dolly.writes, @yakub__m

What is the significance if they occur during stress or recovery?

 Brent: Welcome to this new year today, I have ghetto Yansen and he is with Spriker and I'm very excited to talk to him ghetto. You are the global business and technology. Evangelists for Spriker and which in the blue room or the green room, we talked about that you're the Ben marks of Spriker or the Ben marks of shop where, or the benchmarks of Magento or whatever.  Brent: However you want to say that. Why don't you do a better introduction than I just did. And maybe tell us what you're doing day to day and, one of your passions in life.   Guido: Oh, I have many passions brands. One of wishes now a Spriker indeed. Yeah, my background's in the. I guess to try to compromise a bit that I have a background in psychology and what a usability part of of psychology optimizing a web shop off the debts.  Guido: The study itself at university I'm done. I don't feel that old, but at university that didn't have a lot of online things going on. In terms of examples. So that was mainly about the usability. I could think of thing machine or a way, finding an airports how that works. But I always applied this to align to e-commerce and in, started out with things like mumbo and.  Guido: Wait maybe I am old mama Joomla and a, and I switched gears to to e-commerce and Magento in 2008. That time when we were all playing around with cameras and virtual mark, and those kinds of things that Magento came around, which was this magical thing that was way ahead of its time. And we all add a great fun, I think playing around with that and did that for, 13 years.  Guido: And I think that's also like 20 10, 20 11 that I met you. I think we met at a. It was the Moscone center in San   Brent: Francisco. Could be, yeah. Yeah. The fabric comm X dot commerce.   Guido: This will all be beeped   Brent: out with the knee, right? Yeah. In fact, I was just going through all my supplies. I was going through my old video just getting stuff, getting my mat cleaned up and I found of a video of the, in the intro or the, welcome from the.  Brent: PayPal slash Magento slash whatever eBay people. Yeah. And it was us coming out of the conference center and they all, there's huge. Just all the employees lined up welcoming, everybody to the event. So it was definitely a well thought out event and it was fun how could you go wrong?  Brent: I don't know if if the outcome was what they had expected, but it was fun. And then. A fun event, 2011, definitely.   Guido: Yeah. Events were a fun ride. Remember those events were fun. Now we had a lot of fun with that with Magento organized, a lot of stuff. For Magento we had the Mimi, Japan and Netherlands kickstart this whole global movement of Magento events.  Guido: And I've been lucky enough to to attend many of those those firsts, which are the best I think, to go through like those first events in a country where. People have heard each other's names online on slack or on the forums, but never met in person. So all those awkward first meetings, or those are great to to, attend to.  Guido: And yeah, I and it's also a, the Magento ecosystem is also where I met Boris the founder of Spriker and currently co CEO of Spriker. I think we met sills. 20 11 20 12 had a Magento agency. And some six, seven years ago when you started with we kept in contact and yeah, I would have lost a year.  Guido: I was working at a Magento merchants actually. And he approached me and said, Hey, we're growing like crazy at Spriker and we need someone like you doing community stuff. Spriker we need something like that. So to support that. I don't think you actually build this, build a community.  Guido: I The community is there and does its own thing. That's what we see, which has the rights. But we need someone from Spriker to facilitate what's happening out. There are very similar indeed to what's. What bandage. And before that, around though, we're doing a Magento. So yeah, that's the,   Brent: yeah.  Brent: And I, I did I've interviewed my Miquel Turk for both Spriker and it's an interesting and fun platform and one of the. I had made early on was about the who 15 and how we're working on getting sub one second times. And he laughed at me and he said, yes, Spriker, we're working on sub 400 millisecond times or something like that.  Brent: It is an interesting platform and I'd love to dive into it a little more, but first let's I know that you have been involved with. In conversion rate optimization, I think from an e-commerce standpoint, that is one thing that is often overlooked, especially. A lot of clients will come to a technology partner and they'll say, Hey, I want to build a fantastic website.  Brent: Then they leave those either the technology partner doesn't focus on that or the client doesn't see value in that. So can we maybe just have a brief conversation around, what does it mean for conversion rate and why is that? And so why is that even more important than the platform you're on or the store build that you're doing or any of those.  Guido: I think the conversion rate optimization traditionally it's in the name. It's, a bit limiting. It's the oldest Christian in the Ciroc community. Let's first define what it is. So Euro it's about a practice of semi or semi-truck. Practice or figuring out what works for your online store which usually involves doing user research talking to users, doing surveys, translating those into a hypothesis on what could work and what's, where you expect to be a better for, your store.  Guido: And then validating that through experiments. Usually that's, an AB test. That's, very short description of of, Shiro these days. And I think one of the things that was holding back Shiro, it depends a bit on the depends a lot on the area you're in the business you're in, but for many companies it's, relatively easy to say what the ROI is for buying more ads, buying Edwards.  Guido: This is what I put in. This is what I put out. That's, very straightforward and that's something that then people try to apply to Shiro and that doesn't really work zeroes more. Often long-term strategy, trying to figure out what worked for your customer. And it's really hard to say at the end of the day, at the end of the year what came out of that?  Guido: Exactly. Which is also a bit counter-intuitive because we're doing an AB test. So we can exactly say, this is what version a is doing. This is what version B is doing, but. The course of the year, like if you do three aunts or a thousand experiments what's your contribution? I don't know. And that's that's, sometimes hard for managers to get into and also it can also mean that you're not even growing, but it can also mean that you're not going down.  Guido: So your conversion rate stays the same. Your number stays the same if you're in a declining business like a couple of last years with, if you're in a, in a. Selling holiday houses, like booking.com. It's going to be really hard to increase refresher rates or to, or avenue. But you really need a team like this to understand.  Guido: Okay, what are people still buying? What are the, changing consumer behavior to last year's? And companies that do CRO well those are the ones that can survive this. And if you just keep buying more assets, that's going to be a very difficult thing to,   Brent: to maintain that. Yeah. I think with the Google mistake or the Google ad mistake or the paid ad mistake has always been, Hey, let's just throw money at it.  Brent: And money will also always get it there. And sure. It's true. You can plow enough money into anything to make anything work, but there was a diminish diminishing return on that investment. And I think one thing we learned, I was part of the PayPal mobile optimization program for a year. And we did learn that number one, measuring and doing those tests matters.  Brent: Getting the merchant to get involved and see what's happening. And then I think what you said is you are either not propping up, but finding what works best for you. And then even doubling down on that to make sure that you're putting that investment where it's really paying off, but learning things that are counter-intuitive.  Brent: And I think one of the things that we learned in the mobile optimization. Some of the things that you would think would perform better, perform worse when you think they should perform better. And I think from a from a psychological standpoint or any, type of human behavior standpoint, for me, that's always very interesting to learn.  Brent: Why and why would something you would think performed better perform worse? And I think for the mobile one, I think was all about we're going from this desktop. People have a perception of desktop and then people have a perception of mobile. And I'll just say in the Western world, I'll generalize.  Brent: Most of the time, we're still on our desktop computer buying something it's going more mobile it's compared to the emerging markets where it's, maybe they don't even have a desktop and they're buying everything online. Yeah.   Guido: Yeah and that's counter-intuitive parts saying, okay.  Guido: We think this is going to work with. But it didn't, that's also a big part of why CRO can sometimes be a difficult conversation. Because w with management often, Ciro's also an initially used just to prove whatever management wants it to prove. And that doesn't always work. For example with, booking that I just mentioned that it's booking.com.  Guido: It's you can book hotel rooms there. It's a big company worldwide. It's based in the Netherlands originally. So that's why I use it as an example. There are the example of running experiment. But they, publicly said it. Okay. One in 10 experiments is success. So that even for that company, that's the pinnacle of AB testing and running experiments.  Guido: They're really good at this. And even they well fail nine out of 10 times fill as in doesn't go up doesn't increase your conversion rates or revenue or whatever you're optimizing. So you can imagine if, you don't have your processes in place or you're not as good as booking yet, that number is not as good as one in 10, but might be wanting 21 in 50 or whatever.  Guido: And that's, also I think Bartel for whites white can be really hard to start For companies doing this because you really need to be dedicated. It's not just running a three tests a year and then the hope for the best. That's probably not going to work for you. So that's makes it a bit harder than just buy more Google ads.  Guido: But yeah, you need to realize that. The traffic to your website, that's part one, part two is getting the people on those websites to convert to whatever you want them to buy. And it's still a very important blocking factor if that's not, good. And if you're double the amount of people converting on your websites, that's probably going to stay there.  Guido: Even if you stop optimizing today, if you double that and you're stopped today, it's not going to be we worse tomorrow. Less like things with ads. If you still buy ads today, you're not going to have any traffic any more tomorrow. So that's going to be I think Sierra is going to be in the end.  Guido: There's going to be a better investment, but yeah,   Brent: I think that looking at at what people are doing there, the op the, alternative is not doing. And then you don't even know, then you're really just sailing into a black hole without any knowledge or, thought about what you're doing. So measuring it.  Brent: And I think I've heard is that it's hypothesized, so you can come up with some experiments, you observe those, you measure them and then adjust after. So even, like you said, one in 10 or, one in 20. Those numbers mean that at least you've, found success in that little piece. And normally not normally, but let's just say in the business world if you get a one and 10 on a stock pick and that stock picked does a thousand.  Brent: The increase in your business or your, return? That one in 10 usually pays for the nine. And I think if, as we dig in to CRO and we work in on those specific things with, clients and learn what is doing better, those that one in 10 is going to give a payback. And I'm guessing booking.com does it because it gives them a payback.  Brent: And of course they know their customer.   Guido: Yeah. Yeah. And I think if you're interested, you're all, if you're, like I said you're in an agency you want to sell these things to clients. I think it helps to frame it in a totally different way. Don't, sell it as optimization senators, risk managers.  Guido: And a way to prioritize your backlog. If you run the experiments and you say indeed nine out of 10 would not have works. That may, that means that you save money on implementing those nine things that wouldn't would not have worked anyway. So you don't have to implement them. Just implement the one that does work.  Guido: And, you can also say to the strands that's maybe you think you're not experimenting, but you're changing a little things on your websites today and tomorrow under the author, you still, basically, you're still experimenting. You just don't have any idea what the outcome mess of the experiments.  Guido: The overall sum, you know what happens at the end of the month when you're looking through your books okay, this is what we solve, but you have no ID which. Which of those experiments that you're, I don't know that your content team and what your design team, whatever they or development team, whatever they deployed, you have no idea what those individual experiments contributed to the whole.  Guido: So you're not learning anything. Exactly. It's something   Brent: you can build upon. All right, so let's tie this into Spriker. We, Came on to talk more about Spriker than CRO, but how how we   Guido: can do multiple episodes of breath is found. Good.   Brent: Good good So how well let's, frame it around Spriker and, your role.  Brent: So some of your role is, going to be helping clients and some of your roles building a community.   Guido: It's a bit of a it might, feel like a bit of a career switch, so I'm not, I won't be. So for the last 10 years I've been running those experiments, running hero programs and actually building teams that do this.  Guido: So I won't be doing that. That Spriker at least not, initially. It's, more about the community part. The thing I've also been doing with. With Magento on the side for, 13 years. That's what I'm going to focus on doing doing for Spriker, but it still feels a bit it still feels a bit similar, so I'm not running AB tests anymore, but I'm still trying to.  Guido: To get the best possible feedback out of that community and use that to make Spriker better. And it can be Spriker the product can be Spriker the services that we offer. So in that sense, it's not that far from what I've been doing is Bombi. It won't result in an AB test, only commercial websites.  Guido: But I still plan on running some experiments with the community to see what's working and what isn't, and then collecting that feedback we are building or expanding, facilitating the community that we have. That's a, that's the main goal. Some of the things. That we have. So we have a couple of subgroups within that community.  Guido: We already have a partner advisory board for both the solution partners in the technology part. That's already running. I'm not involved with that. I'm currently working on seating, a customer advisory boards. So that's existing customers getting them to get our coupler, like 15 customers, getting them to get R and R on a regular basis.  Guido: And I get feedback from them on how they use system and help them communicate with Spriker in a better. So that's one thing I'm doing. The second one is regular user groups. So we already had to use a group sets Spriker before the pandemic, those are now being continued on our remote basis.  Guido: So we had our first one last month, which was really fun. Doing that and that's, more aimed necessarily at at the strategy level. There's more day-to-day users that are doing that. The, like most user groups are and a third one is that's working on I'm not sure about the name yet, but like a developer attraction and adoption group.  Guido: So there will be people from, clients, from solution partners and from Spriker itself to she. Okay. What can we do to get, to attract more developers basically to Spriker. We've seen that with, Magento that has, can be quite the bottleneck if you don't have enough developers out in the world.  Guido: So we have a great academy team. That's a surprise. We've got some great courses to onboard people, both for people working in the back ends for developers itself or for people selling selling Spriker those courses that it's something we have. So also I think learning from I'm not the only one from magenta and the spikers and the LA people with Magento background.  Guido: So Carol making sure that Spriker has really good documentation. So that's a, this has been thinking. But the academy, of course only works if people know about Spriker itself, you need to get those developers on board first. And so that's going to be part of that's that third group that I'm working on to figure out, okay, what can we do to onboard more people more developers and get them enthusiastic about the platform.  Brent: It reminds me of the tech stack on spreads. The, what is that? The platform's on, tech beach BHP. Perfect. Yes. So a Magento developer could, he could transition a Spriker or fairly, easy. Yup. Yup. And   Guido: multiple have   Brent: gone sour yeah. It seems to be. I think we've always said this with Magento.  Brent: It seemed like Magento had run the course with eBay and then mark Lavelle and the team came in and, really reinvigorated the community. It seems like red, another tipping point now did an amazing job at that. Absolutely. We're at an another tipping point. So it sounds like some of your role is to listen to what the community is saying and maybe.  Brent: Not adjust commercial aspects of it, put at least adjust communication aspects. Would that be a good realization of, part of your role of how the community is reacting, not reacting, but forming strategy and forward-looking planning in to involve the community.   Guido: Yeah. And of course that's something I experienced in the last 15 years with Magento myself being an active community member, but multiple working on the I'd never worked on the Magento site itself.  Guido: So I've seen something that Magento did really well. I've seen some things I think Magento could have done better. And that's, definitely the part. And one of the first things I said two boars, whatever I'm going to do I won't have sales targets. That's an important one. For this job to work people need to trust you, right?  Guido: That, they need to be able to come with you with open feedback, open open criticism about whatever they think is important for them to continue their journey with with the products and that shouldn't result in a call from the sales department next day, saying. Yeah.   talk-commerce-guido-2022-1-10__22-55-15: Why   Brent: did you do that?  Brent: Why did you say that? I've definitely I've unfortunately, or fortunately had those calls. It does get you. And unfortunately those calls do change a little bit of your direction as a, maybe even as an agency head or as a, or a community organizer in order to get money from. The not from the community, but from that entity and Magento was very good at saying, we're never going to give you money for anything.  Brent: So that was easier. But in in order to get people, let's just say, get people involved. There was a aspect of, we, you need to tow the line. And I agree there has to be some kind of line that has to be towed in terms of don't don't bash us on stage and at a meet Magento event, which actually happened.  Brent: And it should happen when it's something that's egregious. But there are I think there always has to be a commercial aspect to things. And again, so just help educate me. Is there a community version of spark or is it completely commercial?   Guido: It's completely commercial. It's the sources.  Guido: But it's not an open source license. So it the full code is on the, is available and get up for everyone to see and to try and as a and if you're like me too lazy to install it. So there's there are demos available for the different markets that we serve. So we have B to B, to C we have we have marketplace solutions so that's all there for people to see.  Guido: But if you want to use the product, then it becomes a commercial license and that's fully based on either the items sold order. So it depends a bit on the business model and I guess on what's our sales team agrees with   Brent: the clients. Okay. So it's negotiable somewhat.   Guido: Now yeah so, they have it's not necessarily negotiable, but there are levels that you can get to.  Guido: And then of course the better the price becomes lower. Yep.   Brent: Got it. Yeah. Marketplaces is certainly a, big topic right now. Everybody's trying to do a marketplace. I think Magento has made the way Magento is, engineered. Isn't great for marketplace applications. So tell us a little bit about how the marketplace would help a merchant.  Guido: Yeah, and I think w what makes breaker great is that it's, it really focuses on the non standards business models, protocols, the sophisticated business model. And usually with specifically, I think with, marketplace with B to C it's, usually straightforward and there are a lot of platforms supporting that.  Guido: And then you go to B2B or to marketplace usually. And like you said, with Magento You often get into the area of a lot of customizations. And then you need a platform that supports that the business models get more and more diverse, more and more when you go to B2B and marketplace and you need a platform to support that.  Guido: So I think that's one of the, strength of   Brent: biker a Spriker started in Germany. And it's branching out to the rest of the world. So what are. What are your plans now for the U S market? I'm assuming that's the next big market to tackle.   Guido: Yup. So we got our first clients in in the U S and this is definitely, yeah.  Guido: Western Europe and the U S or for many platforms to go to markets, especially if that's one of those countries, your, if you use your own country, U S is a big focus. We have already started there this year. Or 2021 last year and this year 2022 will be a big focus here and we will have we already had an exciting events.  Guido: There are last year, I think we'll have one or two excite events. There are next year for context excites is the spike of fruition of of Magento. Imagine if if that's, if that helps you with with context So that's another, we are definitely focusing on that, but for me personally like I said, the one aspect that I find important is to grow.  Guido: That's a developer base. And specifically for that, I think it's even more important to be a presence. What is feasible in countries that are not Western Europe and the U S because there are a lot of development communities in south America and Africa in Asia, Indonesia, India. And that those are typical markets where marketing or sales is not active or not active yet, or not as active in, in as in Western Europe and in the U S so that's going to be a fun challenge for, me and my team to, see outcome are we are, we can visit get visibility specifically in those markets, but in terms of sales we're growing really fast in in the U S right now, I think this Fastest growth rates.  Guido: Yeah. So it's going to be definitely a big one for 2020   Brent: type of merchant. That would be a good fit for Spriker.   Guido: Yeah. That, that will be the, customer like I said, that has a sophisticated business model and that is a tricky term, I think, because I've met a lot of, I've also worked agency side and every customer thinks they have a sufficient.  Guido: Business model. So that's, always a up for discussion but a typical I think the best suit it's like we just said with B2B and market. Those are definitely the customers that would be a better fit force. Private, I think B2C, although we do have some beets see clients that have more sophisticated mall.  Guido: Sorry if there's, if it requires more customization then then your standard shop, that's definitely a good one. Maybe, a good dimension for context that's Spriker is a password. Oh man. It was on-prem before that we had on-prem we still have some on-prem customers but we only sell the past solution right now.  Guido: So platform as a service and which means we also everything, but there's still a lot of customization that you can still do that you can either have an agency for, we have a lightness partner now. Our orders. You can do in-house if you have a development team in that.   Brent: Oh as I think that past solution and just to educate our audience, the past means that it is a single installation, but it is all, it was hosted by the vendor.  Brent: So you're hosting the platform, you're supporting the base code. But it's the single issue, but it's not shared, it's not an instance that shared like a SAS solution. It's not shared with thousands of people. How do you, then   Guido: you anchor customize it. You can build on top of that compared to with a SAS solution where you can customize some things through settings, but if it's not in the setting, Then you're done.  Guido: Yeah.   Brent: And it's a big difference there. It's the only way to customize that is to build an application that's sitting outside of the application that would con connect via an API. You can't build it directly into the software.   Guido: And a nice addition to that is that's we're going to release. I think there's going to be a Q2.  Guido: I think that was announced. I hope I think Q2, we will release our SDK and AOP. That's the. The application that the platform basically that we will have so then we're going to have our own marketplace, our own app store for things to connect with. Spriker. So then we can have a shared database of whatever you want to connect.  Guido: If you want to connect your your email, your CRM, your ERP to Spriker. You can do that. And I think that's especially interesting because a lot of things in Spriker are interchangeable. So w what the gardener calls package business capability. BBC's which basically means that everything in Spriker it's a collection of those package business capabilities.  Guido: And that's, talk to each other through an API. So if you want to, for example remove that or use your own. You can remove practice checkouts and use a third-party checkout or your own checkouts. And that's different elements in Spriker have. We have I don't know the accounts, but we have several PVCs that consists of several undoes of modules.  Guido: You can just swap them out and especially with the AOP, that will be really interesting because then you can Israel can be relatively well, even more easy to do.   Brent: So coming back to the past model one of the complaints with the Magento version of pass is that it, doesn't necessarily save the client any money on, maintenance because you basically, you're hosting it on Magento, but they'll help support your core, but they won't do anything else then.  Brent: Answer support tickets. So is Spriker taking any different approach to that? Do they, are they doing some of the core updates on the code itself?   Guido: That's a good question. And I don't really, I haven't worked with a Magental spouse version, so I don't really know how to compare it to to that. But yeah, the this Riker core is maintained and it's a it's the same for everyone.  Guido: And you can then choose to update it for you. Yes or no. For all the different models. There are hundreds, I think we're currently over a thousand modules of Spriker itself. They're all versions. You can choose to update. Those were never Whatever works for you. You can you can, of course, ideally update them all when they come out.  Guido: And then that's all on a rolling basis. I think on average, I heard someone say that on average, we have 10 releases a day. That's something I'm definitely that's, being maintained and that you can benefit   Brent: from. So the I, know that speaking to Mike McKell earlier in the year, he talked a lot about the BDB version and then the scalability and the robustness of the platform.  Brent: Maybe tell it, talk to us a little bit about the type of client that would look at B2B and skew counts and things like that.   Guido: Oh, yeah. In terms of we have those extreme examples, and last year at at the, excite conference we had one they have over 550 million sq use in their Spriker store, which I find mind boggling.  Guido: That's that's, very impressive. And yes, people order dare on a regular basis. It's not just sitting there but they they sell electronic parts it's and the case study is actually on my website. If you're interested, it's a sociability and this is the name of the. That's the platform.  Guido: And yeah, I think In terms of, and that's, why I think Spriker is very interesting to me personally. I was funded and that there's already, there's something I found with, Magento. I funded the B2B sites, that those those clients always way more interesting PTC sites because of those those tricky business models and the tricky Details that you need to get right in, B2B.  Guido: B2C can be hard with a lot of customers. Just the sheer volume of, customers. If you have a lot of shopping that those customers of customer behavior change can change fast, but with B2B also have this and the detail that you need to get, right? All those specific things for your business.  Guido: I was Working with a company that did prince and they printed basically on that. And that means that if you print on everything, it's really hard to get templates for, printing. I know, yeah. Umbrella umbrellas, that's a different cars. You can mugs pens, everything, all the merchant you can think of that they would print it.  Guido: And which, meant that it was basically almost all manual. For, the depends that some, automation but basically everything else was done manually, which is mind blowing, but then you need to keep in mind when, someone orders it they had their, our local supply was in the.  Guido: But if, you didn't need a speed delivery, so if you needed a speed delivery, they would do that in a, in the Netherlands. And then you'd have an extra fee for that. But if If you would want to deliver, like in one and a half, two weeks, they would actually ship all the stock that was in the Netherlands.  Guido: Put it on a on a truck, drove it to Poland, and then there are people would unpack everything print it, put it back in a truck, drive it back to the Netherlands and. Because it was so labor intensive, that was actually cheaper to do that than just to print it in the Netherlands, which again is mind blowing, but then you need a system, a backend that supports crazy shit like that.  Guido: And, that's what I find interesting. Those, clients of debt, those are the things that are holding. Or, things your system is holding you back on? I think that's those are great cases for Spriker.   Brent: Yeah, same example that we worked with the eyeglass company that had the same idea where they, want part of the eyeglasses would get done in a factory, in one part of the city.  Brent: And then it would get shipped across town to put the lenses in the frames or whatever. Then they get shipped to the retail store, get shipped back, and then. Then get shipped to the client directly. If that's that's the if that's the model that they had. And that was I know that for Magento, that turned out to be very complicated.  Brent: But, yeah. So I can see how that would from a standpoint of complexity and from a platform where you that's, where you, the necessity of having a platform that you can modify and make your own. Essentially,   Guido: if you want to do a. What we call unified commerce. So your terminals in your stores, your physical stores, where people can can order stuff or clients can order stuff locally.  Guido: And that's connected into your system complexity rises quickly. And also things like in the beginning with, Magento Magento was fixed right now, but in Magento in the beginning it was all already really hard to have multiple warehouses. There's also, it was also another thing.  Guido: And luckily Spriker fixed that from beginning. That's, something. We have a lot of clients that's a doer multiple millions of revenue. That's the things they want to fix and expect from from a platform to. Yeah, it's F as a default.   Brent: There's a whole bunch of buzzwords floating around in the community on monoliths and microservices and micro blah-blah-blah PWA.  Brent: Where is Spriker sitting in on that. And I guess from a technology standpoint, is it easier for a customer to get into it and not worry so much about the technology? Or are they going to have to. Not worry there's going to be a certain amount of development needed to get things running.  Guido: It's a past platform so, there will always be some some development needed to get at the Oregon. Although we do have a. We do have for there's a front end that you can use if that's what you want, but you can also add your own phone tents. It will need to be connected to, the data that you have or data that you have needs to be important.  Guido: So those are always things that, that needs. And yeah, there are a lot of buzzwords and it can be complex can get complex really fast. I'm still struggling with it myself. And honestly, the first time I heard the term monolith was with the open letter the Magento Ruthie last summer, they started complaining about how things were going and partially rightfully and that's where I I formed encountered the term monolith before, but just disregarded it and then, but that, wasn't the first point. I thought I need to look into this and then, oh, this is what they mean, but yeah for, a Spriker I think Spriker is more something that's often listed in the.  Guido: Corner of things, a mock standing for a microservices, API, firsts cloud something and a cloud native and and, the headless. So those are also for. Yeah.   Brent: Excellent.   Guido: But that's, like a, term that people use often. We, were not fully onboard with the microservices part of that that equation Spriker believes more.  Guido: And that's what I just mentioned with, the package business capabilities. Microservices first will mean that everything is a microservice. That that leads to a lot of overheads very quickly. And that's, not needed for most companies. And there are always exceptions. But it's not something that you'd benefit from.  Guido: And then on the other end of the spectrum is the, monolith like a magenta was at the. Mainly and then Spriker sits, in the middle, which we find very comfortable and most lines seem to be for most lines. It seemed to be a nice balance between the flexibility that you would get with a, with API first and microservices.  Guido: But to have those package in things that make sense for the business package business capabilities. It's not a developer term. It's, business. It's a business term. Alexa, you're you to have a package business capability for you can have a CRM or an ERP or your checkouts or your phone tense.  Guido: Those can be different, capabilities of your system. And for, clients that just makes more sense. That language makes more sense and the way at least Spriker has built a, it also prevents the overhead that, you would get with only using microservice.   Brent: Yeah. I like that term, a package business capabilities.  Brent: Yeah, it gives the I think it, the idea of behind that is. You don't there. There's going to be a lot of solutions that would apply, but you don't necessarily have to do the customization, but if you need to, you still can. So clients or merchants can feel better about. Making their solution work at a lower cost or at least a lower initial investment to get them up and running.  Brent: Yeah.   Guido: And the Spriker is also not. It's targeting the local bakery rights. That'd be fair. It's we're, targeting a larger enterprise businesses mainly and those usually. Either an agency or their own development team that, can handle this. And that's also where I think Spriker shines.  Guido: A lot of developers love working with Spriker because it's so maintainable for them, they only need to focus on those extra things that are the, exceptions basically for their business and not necessarily maintaining the system behind us. That's also not something I'm not a developer, but a.  Guido: Recurring daily tasks, not something necessarily that you're looking forward to for doing for most people, at least I'm generalizing here, but most people the new things, that those are the challenging things. That's what you want to do with most developers want to do. And that's, what we enable.  Guido: And, along those package, business capabilities, one thing I I think you need to mention that's not something that's probably grant funded or something it's a term developed by by Gardner Spriker was also they recognized Spriker as a, as efficient, airy in their magic quadrants last year.  Guido: And it's only the second year that we, that the sparkle was even listed. And the magic quadrants. And we're already we were spoken was the platform. We moved the most distance in a positive direction within that. Within the quite uncertain, there was really nice, but also if you look at this quadrant the market changed so much compared to when we started with Magento.  Guido: Like I said, with Magento, we had commerce where we had virtual mark and there was Magento And we had a couple of like Intershop or those kinds of more commercial packages. But right now the magic quadrants, the market is so different than Demetric wardens already contains like 16, 16, 17 systems.  Guido: And that's like the creme de LA creme from, what gardeners selectors are the F right now are the hundreds of solutions that you as a company can pick. That's a huge challenge, I think for both developers, both an agencies and clients to say, what on earth do I need to a, big year? A lot of we saw all of you included agencies that's select a platform, right?  Guido: And you need to stick to dads and that's what you invest in. And that's what you then hope sticks when for, long enough. But also in, in debt, I think. And of course I am definitely biased in this in-depth. Spriker is positioned really well because it's so open with the API, with those package B business capabilities there's relatively easy to adopt for you as an agency or develop our work lines that fits really well with with whatever you have, right.  Guido: With the adjacent tools for e-commerce that you need to connect with debts because it's focuses only on the, on you bringing development through the table for, everything that's specific to your business and enabling that. I think that positions us   Brent: really well.  Brent: Five 10 minutes left here. What are you excited now for 2022? What do you see coming on the e-commerce horizon on the technology horizon? Do you think? I think one thing you mentioned is that there's so many more technology players in that magic quadrant and it's, you would think that we'd be seeing some more consolidation, but it's almost as though we're splitting it between SAS pass and on-prem, and then everybody.  Brent: There's more of them. So what, do you see happening in 2022? What's exciting. More and more. Yeah,   Guido: this is very exciting. I, do think and, actually I had the same thing with magenta. I never looked at other platforms and look the oldest competition that we need to fight. Those other platforms.  Guido: Apparently. The e-commerce market is huge and we all get to play a part in that. And there's this place for almost all of us or these, a lot of us there is place for, Magento and there's place for, a shop where there are a lot of business cases, that's fifth with those, and we don't necessarily need.  Guido: Bethel each other. And in a ring and the bolt flying everywhere that this was really needed. I think we can all focus on that's the thing that we really good at. And looking at how fast Spriker is going in terms of clients and employees I'm not worried about that.  Guido: That's a very exciting thing to be at. I'm actually for the past forever, every ever since I've. The works basically. I had this dream once working for like a SAS company, like Dropbox or Evernote that those were the companies I thought 15 years ago, that will be really cool to work at. So I have a, single piece of software and you can optimize debts and both from a usability perspective, but also you have this endless nearly endless world markets and form of your, that you got, that you can conquer that there will be really exciting.  Guido: And that's, this is what I am excited about. This is my first time working on the platform sites and, doing this and Applying my, my experience with, community building for the first time in actually a professional way. I They actually paying me for this now, especially my dream job that had been doing on the side for, 13 years now.  Guido: So I'm very, excited about that. And it's a great spot to be in with, Spriker it's it's very they're, remote first. I've been working remote first for, but at least pre Corona, but four or five years. But it's, so natural to the company. It's everyone is remote first have with limited holidays.  Guido: That's always nice to have I'm working work from Netherlands. I don't have to complain and we already. Twenty-five holidays by default. So nothing to complain there, but it's still nice to have, especially we have to, to kids like I do sometimes you need, you just need some extra because they're the home again.  Guido: And And, building that community. And like I said, w what I really enjoyed with the Magento community, bringing people together, especially for the first time, I does have a lot of community first next year. And the awkward moments, the recognition. That's exciting starting point at five that you see where people first meet the immediate charter and then build businesses based on that.  Guido: I clearly remember the first meeting magenta are organized in the Netherlands. To developers came to get our metadata for the first time. And now they have this huge Magento business that they sold a couple of years ago. And, that's happened multiple times and that's really exciting to me to see that's happening and then to be at the start of that.  Brent: Yeah, I agree. So I like the idea of having an MMA. MMA cage match, but you'd call it Magento, meet Magento association, cage match, and we'd get Spriker and shop wire in there. And we'd just get some we just have a Throwdown and see who wins. That's that's one way to look at it.   Guido: That's one way to look at it.  Guido: Like I said, I don't necessarily need a cage measure. I think we're, I think we can all we're all in e-commerce. So that's, a really good choice to begin with. And I think if we play at rise, we will all win big. What would be   Brent: a buydown instead of a Throwdown? I think. So we as, we close out, I always give people an opportunity to do a shameless plug.  Brent: What w shameless plug is just, you can promote anything you'd even a local school or charity or whatever it is that you're, thinking about the.   Guido: I feel like I've been shamelessly plugging Spriker for us lost at least 20 minutes already. Yeah, but if you want me to continue with that, we have we have for looking for a lot of people.  Guido: As, everyone in the in the e-commerce sphere is, so if you're interested in in dance and now working for a great European employer have a look at the Sprocket. Hiring people work white likes. That's where we are remote first and work from anywhere. So a take your pick if you're interested, definitely take a look there.  Guido: And on a personal note, we started out with a CRO. I have my podcast on the, on CRO still. It's a weekly podcast interviewing experts in the field and that's the last hero. So I have looked there and you probably already into podcasts anyway, since you're listening to this, so might as well subscribe.  Brent: Absolutely. Yeah. We all need to share our subscribers and get people to listen more and learn more. I think that the, at first first this should be education. This should be learning about other platforms is not about Magento or whatever. The place where we can learn about what other platforms are doing.  Brent: And from my personal for 2022, I'm super interested in CRO and I have seen sodas seen the light and, why that's so important for clients. So I applaud you for what you've done over the years. And just as a plug. You did organize the first meat Magento, right way back in 2009,   Guido: January 27th, 2009.   Brent: Wow.  Brent: Yeah, that's amazing. And it's, been such a fantastic journey for both the community building, which has been the most important part for me. Because that's when I got introduced to right about that same time, that's when I got introduced to Magento. And I think that community is what has driven the Magento to where it is.  Brent: And you have to give a lot of a lot of kudos, so to speak to the community for helping move that along. And right now there's a lot of A lot of communication that isn't and is happening in the Magento community.   Guido: Yeah. Yeah, I do think community a, is a huge asset for, you as a company, whatever you're doing as a as a company community is one of those things that is the hardest to copy.  Guido: It's all of us can copy your product. They can copy your servers, your pricing model, your business model. But it's really hard to copy a, community. And I think that's also the, one of the big reasons magenta was still so big, even with all those comp the competition that's out there in, in that 14, 15 year that Magento was existing.  Guido: Something better probably has come along. And, maybe it has For that specific business model. But transitioning all those agencies away from, you or the developers to learn something new or clients to switch platforms. Clients don't switch platforms every year. There's, a time delay in that and, it gives them that gives you the opportunity to, improve your product again, because you have that community commitment from people through you in the company.  Guido: And that's Yeah, I think I mean with Adobe taking over Magento right now, they're well, they're not investing in the name Magento anymore. That's I think that's abundantly clear with removing the name from the website. The logo was and magento.com now redirecting to to the Adobe website.  Guido: But, even for, the product It's. Yeah, it's hard to see a little of investment from, Adobe. What we hoped would happen when they took over. But still everyone's using Magento. And it's really hard. You, as a business owner, you or the Magento agency, it's really hard to have everyone trained on a different, platform.  Guido: That's not necessarily something you're looking   Brent: forward to. Yeah. That's so true.   Guido: Yeah. And so communities is a huge assets for four years of community. And then for user, as a business and that's community, then in a broad sense, a sense of the word can be individuals, developers, the companies that, are attached to you and committed to   Brent: I think I get your name right there, ghetto Yonson.  Brent: Thank you so much for being here today. Ghetto is the global business and technology evangelist for Spriker. I look forward to seeing you in 2022 in person, somewhere in the world. Hopefully in the U S or in Europe maybe even at a race, we can do a race together. We did, we got through this whole episode without talking about running.  Brent: Next time we'll do more of that. I appreciate you being here today. Thank you.   Guido: Thanks for having me.   Brent: Thank you.

This week's View examines whether high-grade premature ventricular contractions (PVCs) during stress testing predict mortality in asymptomatic individuals; trends in transcatheter mitral valve therapies in the United States; and key perspectives on the newly released ACC/AHA/SCAI Coronary Revascularization Guideline.   Subscribe to Eagle's Eye View

Learn all about what’s new in today’s Kubernetes 1.23 with its release team lead, Rey Lejano. Rey is a Field Engineer at SUSE/Rancher Labs, and a contributor to the Docs, Release and Security SIGs. Long time listener Adam also drops by to ask Craig what’s been happening with the hiatus. Do you have something cool to share? Some questions? Let us know: web: kubernetespodcast.com mail: kubernetespodcast@google.com twitter: @kubernetespod Chatter of the week Ted Lasso Filming locations Knative applies to become a CNCF project Links from the interview African clawed frog Cross-fertilization and structural comparison of egg extracellular matrix glycoproteins from Xenopus laevis and Xenopus tropicalis ITIL RX-M 1.18 release team 1.23 release team Kubernetes 1.23: The Next Frontier Odd numbered Star Trek movies Star Trek V: The Final Frontier SIG Release Charter Enhancements: Dual stack IPv4/IPv6 - Stable Pod security admission - Beta TTL After Finished Controller - Stable Auto delete PVCs created by StatefulSets - Alpha Skip Volume Ownership Change - Stable Generic Ephemeral Inline Volumes CronJobs Deprecation of FlexVolumes Deprecation of klog flags HorizontalPodAutoscaler v2 API - Stable Ephemeral containers - Beta kubectl events improvements - Alpha Kubelet CRI support - Beta 1.22 interview with Savitha Raghunathan 1.23 lead: James Laverack Kubernetes Contributor Celebration Rey Lejano on Twitter

In this episode of the Heart podcast, Digital Media Editor, Dr James Rudd is joined by EP specialist Dr Bhargava from the Cleveland Clinic. They discuss his Education in Heart paper on PVCs, covering assessment, drugs and ablation. If you enjoy the show, please subscribe to the podcast to get episodes automatically downloaded to your phone and computer. Also, please consider leaving us a review at https://itunes.apple.com/gb/podcast/heart-podcast/id445358212?mt=2 Link to published paper: https://heart.bmj.com/content/early/2021/07/13/heartjnl-2020-318628

PVC is known as Poison Plastic. It falls under the category of synthetic plastic polymer. PVCs are non-biodegradable; current disposal options include burning which releases toxic fumes that have serious implications on public health. Another option is to send them to the landfills as waste pickers do not earn anything from the discarded flexes. It is said that PVC contaminates humans and the environment throughout its lifecycle: during its production, use, and disposal & most of us are ignorant of this information. As per The Times of India, 90 % of all advertising in India in 2017 was done on PVC. On an average, around 18 tonnes of PVC flex is consumed per month. Today this industry is almost linear in nature however let's understand what a circular business model here would look like. When you are on a drive, you come across direction signs, if you are on the expressway or even in a tech park, you can identify building names written in bold that can be identified from kilometers away, when you are in a shopping mall, you notice each brand has a specific layout in their store the feel of which stays common no matter which part of the country you are...this forms a part of visual branding. Next when you are at a petrol pump you notice, so many signs or boards that talk to you silently...can you remember a few? All of these are known as visual identification and this is the exact portfolio of Vivenge, the company we are talking about today. Vivenge is a Poland based signage company that has embarked on a sustainable rebranding process. Currently the company is a one-stop-shop for durable visual identification as they provide both outdoor (outdoor signage, small architecture) and indoor visual identification (durable indoor signage, furniture, small architecture) as well as related services (e.g. installation, logistics). They have been in business since 1997 and currently its clients comprise 48 brands in 9 countries. Listen to the episode to understand how they are implementing circular business models. Source : http://r2piproject.eu/circularguidelines/wp-content/uploads/2019/10/R2pi_Vivenge_final2.0.pdf; http://r2piproject.eu/circularguidelines/wp-content/uploads/2020/04/Vivenge-Case-Study.pdf; The Better India article Keyword : What is a circular economy? Follow our page- (Circular Business Podcast | The Circular Collective) Reach out to us on LinkedIn | Facebook | Instagram | Twitter --- Send in a voice message: https://podcasters.spotify.com/pod/show/circular-business-podcast/message Support this podcast: https://podcasters.spotify.com/pod/show/circular-business-podcast/support

For this week's Feature Discussion, please join authors Igor Klem, Pasquale Santangeli, Mark N.A. Estes III, and Associate Editor Victoria Delgado as they discuss, in a panel forum, the articles: " The Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients with Non-Ischemic Cardiomyopathy," "Prognostic Value of Non-Ischemic Ring-Like Left Ventricular Scar in Patients with Apparently Idiopathic Non-Sustained Ventricular Arrhythmias," and "Cardiac Magnetic Resonance Imaging in Nonischemic Cardiomyopathy: Prediction Without Prevention of Sudden Death." Dr. Carolyn Lam: Welcome to Circulation on the run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate editor, Director of the Pauley Heart Center in Richmond, Virginia. Well Carolyn, this week we've got another sort of double feature with a forum and our focus is going to be on myocardial scar that's observed with late gadolinium enhancement during cardiovascular magnetic resonance and the two author groups we'll be discussing the impact of that scar on the development of ventricular arrhythmias. But before we get to that, how about we grab a cup of coffee and jump into the other articles in the issue? Would you like to go first? Dr. Carolyn Lam: I certainly would. Although I have to say, can't wait for the double feature. I love those, and this is right up your alley too. All right. But first, the first paper I want to talk about provides new randomized trial information regarding the benefits of catheter ablation in atrial fibrillation in patients who also have heart failure. Now, this is a sub-study of the CABANA trial. Dr. Greg Hundley: So Carolyn, remind us a little bit about the CABANA trial first. Dr. Carolyn Lam: I thought you might ask. Well, CABANA randomized 2,204 patients with atrial fibrillation who were 65 years or older or less than 65 with one or more risk factors for stroke at, it was huge at 126 sites, and they were randomized to ablation with pulmonary vein isolation or drug therapy. Now of these, 35% of 778 patients had New York Heart Association Class II or higher at baseline, and really formed the subject of the current paper. Although this sub-study was not specifically designed to evaluate patients with heart failure with preserved ejection fraction, about 91% of the patients with a clinical diagnosis of heart failure participating in CABANA for whom such data on injection fraction were available, really had an ejection fraction of above 40% and fully 79% had an ejection fraction above 50%. So excitingly, this is really majority talking about, have HFpEF. Now, what did they find well in patients with New York heart Association Class II or III heart failure at trial entry, most of whom did not have a reduced ejection fraction. Dr. Carolyn Lam: There was substantial clinical outcome benefits with the ablation over drug therapy with a 36% relative reduction in the primary composite endpoint of death, disabling stroke, serious bleeding or cardiac arrest. Benefits were evident for both all-cause mortality and atrial fibrillation reduction. However, the effects on heart failure hospitalization were small and not significant. Authors also caution that these results should not be viewed as practice changing until they are reproduced in a confirmatory trial of ablation in the same population. And this is beautifully discussed in an editorial by Lynda Rosenfeld and Alan Enriquez from Yale University School of Medicine. Dr. Greg Hundley: Oh, wow. Thanks Carolyn. Well, my first paper comes from the world of basic science and it's from Professor Thomas Braun, from the Max Planck Institute for Heart and Lung Research. So Carolyn, vascular smooth muscle cells show a remarkable phenotypic plasticity allowing acquisition of contractile or synthetic states, but critical information is missing about the physiological signals that promote formation and maintenance of contractile vascular smooth muscle cells in vivo. So BMP-9 and BMP-10 are known to regulate endothelial quiescence after secretion from the liver and right atrium. And these investigators are studied the role of BMP-9 and 10 for controlling formation of contract, all vascular smooth muscle cells. Dr. Carolyn Lam: Greg, talking about vascular smooth muscle cells always reminds me of their role in pulmonary hypertension, am I right? Dr. Greg Hundley: Yes, Carolyn. So these investigators found that in mouse models, BMP-9 and BMP-10 act directly on vascular smooth muscle cells for induction and maintenance of their contractile state, and surprisingly the effects of BMP-9 and 10 in vascular smooth muscle cells are mediated by different combinations of BMP type 1 receptors in a vessel bed specific manner. And therefore, just as you suggest, Carolyn, these results may offer new opportunities to manipulate blood pressure in the pulmonary circulation. Dr. Carolyn Lam: Thank you, Greg. Well, my next paper provides the first proof of principle of gene therapy for complete correction of Type 1 Long QT syndrome. Dr. Greg Hundley: Ah, so tell us a little bit about Type 1 Long QT syndrome, Carolyn. Dr. Carolyn Lam: Okay. Well Type 1 long QT syndrome is caused by loss of function variants in the KCNQ1 and coded potassium channel alpha sub-unit. And that is essential for cardiac repolarization providing the slow delayed rectifier current. Now no current therapies target the molecular cause of this Type 1 long QT syndrome. Well, this study from Dr. Michael Ackerman colleagues from Mayo Clinic Rochester really established a novel dual component suppression and replacement KCNQ1 gene therapy approach for Type 1 long QT syndrome. And it's the type that contains the KCNQ1 short hairpin RNA to suppress endogenous expression and a codeine altered short hairpin RNA immune copy of this KCNQ1 for gene replacement. Dr. Carolyn Lam: So this very novel approach rescued the prolonged action potential duration in inducible pluripotent STEM cell cardiomyocytes derived from four patients with unique Type 1 Long QT syndrome, causative, KCNQ1 variants. So it's super cool. Just go have a look. Dr. Greg Hundley: Well, thanks Carolyn. Dr. Carolyn Lam: I want to also tell you about other things in the mail bag. We have ECG Challenge by Dr. Dai on “Severe Arrhythmia Caused by a Chinese Herbal Liqueur. What's the Diagnosis?” I'm not going to tell you. You have to go see. We have Dr. Karen Sliwa writing a beautiful Joint Opinion paper from the World Heart Federation and American College of Cardiology, American Heart Association, and European Society of Cardiology on "Taking a Stand Against Air Pollution, the Impact on Cardiovascular Disease." Dr. Greg Hundley: Well, thanks Carolyn. So I've got a couple other articles. First Professor Yacoub has a global rounds describing and working towards meeting the challenges of improving cardiovascular health in Egypt. Those are really interesting features to learn about cardiovascular care worldwide. Next there's an In Depth article by Professor Thum entitled, "Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases, Roadmap to the Clinic." And then finally, a Research Letter from Dr. Bottá entitled, "Risk of Coronary Artery Disease Conferred by Low Density Lipoprotein Cholesterol Depends on Apologetic Background." Well, Carolyn, what a great issue and how about now we proceed on to that double feature? Dr. Carolyn Lam: Oh, I can't wait. Thanks Greg. Dr. Greg Hundley: Well, listeners, we are here for a really exciting feature discussion today that's going to focus on imaging, in particular magnetic, resonance imaging, and some new findings in that era and how those findings may pertain to ventricular dysrhythmias. With us today, we have Dr. Igor Klem from Duke University who will be discussing a paper, Dr. Pasquale Santangeli from University of Pennsylvania, our own associate editor, Dr. Victoria Delgado from Leiden and an editorialist, Dr. Mark Estes from UPMC in Pittsburgh. Welcome to all of you. Well, Igor, we're going to start with you. Could you tell us what was the hypothesis for your study and what was your study population in study design? Dr. Igor Klem: Yes. Good morning, Greg and thanks for the invitation. We wanted to know if you have a patient who you diagnosed with non ischemic cardiomyopathy based on clinical grounds and you refer him for a cardiac MRI study with contrast, what is the additional information that you get from the MRI study? And so we wanted to compare, and that's primarily related to the findings on scar imaging with late gadolinium enhancement. And we wanted to compare that to one of the most robust clinical parameters in cardiology, which is left ventricular ejection fraction, and in particular using a cutoff of 35%, which somehow in our clinical management has sort of as established as a break point for many clinical decisions. Dr. Igor Klem: And so we created a registry among three centers of patients who undergo a cardiac MRI study, where we found an LVEF of less than 50% and we followed them for a number of outcomes. One is all caused death. And then we wanted to separate a little bit the events into those who have cardiac mortality to look at a little epidemiology because in those patients, we have two major adverse events: one as heart failure related mortality. One is arrhythmia related mortality. Dr. Greg Hundley: And how many subjects did you include? Dr. Igor Klem: We included about a thousand patients from three centers and coming to the major findings of our study, we found that both left ventricular ejection fraction, as we know, is a robust marker of all cause mortality and cardiac death. And so it was the presence of myocardial scar on cardiac MRI. But the major difference was in relation to the arrhythmic events. We founded left ventricular ejection fraction in particular, when we use the 35% cutoff actually had very little predictive power to inform us who is at risk of arrhythmic events. In contrast, there was a very strong and robust relationship or multiple statistical methods to stratify patients who are at risk for sudden cardiac death, appropriate ICD shock, as well as arrhythmic cardiac death. Dr. Greg Hundley: Very good. Well, Pasquale understand you also performed a research study utilizing cardiovascular magnetic resonance. Could you describe for us your hypothesis as well as what was your population and your study design? Dr. Pasquale Santangeli: Thank you, Greg. And of course, thanks to the editor for the interest in our paper. I need to thank also the first call authors Daniele Muser and Gaetano Nucifora for putting together a registry of 70 institutions throughout the U.S., Europe, and Japan and the our hypothesis came from a clinical need. We do know that patients with idiopathic ventricular re we ask, which includes not sustain a weakness like PVCs or non-sustained VT. Very few of them, but there is a group of them that have a higher risk of ending malignant and up comes in terms of your ethnic events over follow-up. And prior studies have shown that by doing an MRI and showings and the detecting scar related announcement, there is an increase with how we make events of a follow-up. However, if you do look at those studies late, an answer's been reported in up to 70% of these patients, which you never view is a highly practical way of re-stratifying these patients, because you have a risk factor that is present 70% of those, then it's hard to use it for clinical decision-making. Dr. Pasquale Santangeli: So in this registry, which you put it again at 686 patients with panel data idiopathic, not sustained ventricular arrhythmias, which were defined by a normal WBC gene status, a normal echocardiogram and a normal stress test. We looked at whether there is a specific pattern of late announcement. So how basically I believe lands, and it looks on the MRI, they may predict better or outcomes over follow-up. And again, we use a composite and Pauline the full cost mortality, but associated cardiac arrest due to ventricular fibrillation or a hemodynamically unstable BP, or in a subgroup of patients that underwent ICD therapy. We also looked at, I approve SED shocks. Dr. Pasquale Santangeli: The groups were divided in three different categories. The first one, which is a larger group of 85% of patients and no late announcement. The second group, the one with late announcement, which represents the remaining 50% of 15% of patients, we divided it into a ring light pattern, which was defined as that word says, as a ring like distribution of the lead announcement in the mid-market segments, which involves a three consecutive continuous segments in a short axis view. It looks like really at least half the ring or three-quarters of the ring. Dr. Pasquale Santangeli: And the other group is the one that had the leader announcement without a ring light pattern. And it's interesting that the third and the latest announcement was not that similar between the ring light and the one without ring light late announcement. What we did find though for our follow-up the patient with a ring light pattern, a significantly higher rate of the primary composite endpoint, which happened in the median follow-up about 61 months so it was quite long. And the composite outcome occurred in 50% of patients in the ring light group versus 19% in the no ring light a positive announcement group and a 0.3%. So really, really rare in patients. So then concluded that of course, late announcement does provide some information in general, particularly the type of announcement that increases the risk significantly. Probably although this has to be confirmed prospective fashion patient with a ring light pattern may benefit from other forms of interventions, including potentially defibrillator therapy in a prophylactic fashion. Dr. Greg Hundley: Very nice. So now listeners, we're going to turn to our associate editor. One of the imaging experts here at Circulation, Dr. Victoria Delgado. Victoria, you see a lot of papers come across your desk and as an imaging expert, what attracted you to these two papers? And what do you think are their significance? Dr. Victoria Delgado: Thank you, Greg. I think that these two papers are important because right now, if we follow the clinical guidelines, we decide implantation. For example, of an ICD based on the ejection fraction, and we see that in many patients based on ejection fraction, they may not benefit ever from an ICD because they don't have arrhythmias. What other patients who do not meet the criteria often injection fraction below 35%. They may have still arrhythmias. So the article by Igor highlights the relevance of the amount of burden of late government Huntsman with CMR, in patients with non ischemic cardiomyopathy, which are sometimes very challenging patients on how to decide when we implant an ICD or not. We need sometimes to base the decision on genetics. Dr. Victoria Delgado: If we have an on the other hand, the paper of Pasquale, these were patients with normal echocardiogram. So what patient, having arrhythmias where we don't see on echocardiogram, that is the first imaging technique that we usually use to evaluate these patients. We don't see anything, but CMR can give us more information in terms of structural abnormalities and particularly not only the burden of scar, but also the pattern of the scar. And we have seen in other studies that for example, not only for ICD implantation, but for ventricular tachycardia ablation. The characteristics of that scar and some areas where these are short of panel that can be targeted for that ventricular tachycardia ablation can lead to much more precise treatment if you want of these patients. Dr. Greg Hundley: Thank you, Victoria. So it sounds like listeners we're hearing late gadolinium enhancement, regardless of EF could be forecasting, future arrhythmic events. And then also the pattern of late gadolinium enhancement, where contiguous segments in a ring-like fashion may also offer additional prognostic information. Well, now we're going to turn to our editorialists and as you know, listeners at Circulation, we'll bring in an editorialist to really help put things together and uniquely here today, we have Dr. Mark Estes, who is really not an imager per se, but like many of us uses the information from imaging to make clinical decisions. Mark, how do you see this late gadolinium enhancement as perhaps a new consideration for placement of devices? Dr. N.A. Mark Estes: Greg, that's one of the key questions. There's no doubt, not only based on these two studies, which extend our prior information about LGE and patients with valid and non ischemic cardiomyopathies that scar burden is important in predicting not only total mortality, but arrhythmic events. All of the criteria that were used in the original ICD studies, which include the definite, the Skuid half Danish and made it our it trials use only ejection fraction and functional status, no imaging. These are legacy trials. Now, many of them, a decade or more older. And the treatment of advanced heart failure has progressed to the point that the total mortality is dramatically lower than it was at the time of these studies. In some instances down to 4 or 5% per year. The studies are important in that they identify a subgroup of patients with low ejection fractions, less than 35%, who might qualify for ICDs, who are unlikely to benefit. Dr. N.A. Mark Estes: They also identify a group of patients with preserved ejection fraction greater than 35%, less than 50 in whom the risk of sudden death may be substantial. And it extends prior observations about patchy, mid Meyer, cardio wall fibrosis, subendocardial, subepicardial and important ways. But the key issue here, and it was alluded to with Pasquale's comments about prospective validation, is that when one has a risk stratifier and identifies a high risk population that has to be linked to an unequivocal therapy, it improves survival. And we don't have that link quite yet. Dr. N.A. Mark Estes: Prospective randomized trials are unlikely to be done in the low ejection fraction because they would probably be considered unethical. Given the trials that have shown the benefit you can't randomize to defibrillator versus an implantable loop recorders. I think the future really lies in risk stratification for people with preserved ejection fractions greater than 35%, less than 50 using LG in that patient population. Currently, I think the best information we can give to clinicians is to stick with the AHA guidelines, which is PF less than 35% with dilated, nonischemic class II symptoms who have had optimal medical therapy for at least three months using perhaps in that patient population LGE for shared decision-making in patients about the magnitude of the risk. And I think that's as far as we can go pending future studies, and there is one which we can discuss later on the CMR study at just that preserved ejection fraction LGE randomizing to defibrillator versus ILR. Dr. Greg Hundley: Thank you, Mark. So listeners just really quickly, let's go back to each of our experts and ask them, you know, in 20 seconds, Igor, Pasquale, Victoria, and Mark, what's the next study that needs to be performed in this space? Igor, we'll start with you. Dr. Igor Klem: Well, number one, following on Mark's comment on the less than 35% population, I think that it's unlikely that they're randomized clinical trial is ethical in this population, but we may consider a wealth of registry data by now that shows that there is a subgroup of patients who have a lower risk or lower benefit from an ICD. I think in the preserved ejection fraction above 35%, maybe up to 45%, 50%. That's an interesting study that's coming up. Maybe there's more trials that can provide us that robust information that we need today in order to change the guidelines to risk stratify, not based on the LVF, but on the presence of scar or maybe subgroups of scar. Dr. Greg Hundley: Pasquale? Dr. Pasquale Santangeli: Yes. So I think of course, one of the major studies is the one already alluded by this, which is a prospective study that links as specific therapy like ICD or even additional risk factors like we've been using program's stimulation some of these patients to further risk for the five to see what they can benefit. Dr. Pasquale Santangeli: Based another one that I think is important for the study that we did is a mechanistic more study to understand why the ring light pattern was there, as opposed to other patterns. We do believe we think that some of these patients may have an initial form of lb dominant arrhythmogenic paramount. There wasn't really a detective before and ran. Now, if we actually extending our study and have a registry to try to screen also the family members or patients with ring light pattern to understand whether there is a familiar component to it, because really we do not see this type of pattern that commonly and it'd been associated with lb dominant. Magnetic kind of alpha in some others, small studies. Dr. Pasquale Santangeli: So that's the other part to dig in a little bit more into the field type for these patients to understand why one pattern versus another happens and whether that gets main to, to explain why there's a higher risk in one population versus another. Dr. Greg Hundley: Victoria. Dr. Victoria Delgado: Yeah. Following what has been said. I think that from the imaging point of view, we are always criticizing in a way that we increase the burden or the cost of healthcare. But I think that these studies or any randomized study where MRI or echo is used in order to design a therapy and show the value of using that imaging technique to optimize the health care costs is important. So I will not add much on which sort of populations, but probably patients within non ischemic cardiomyopathy with preserved ejection fraction that do not fulfill the recent scores, for example, in hypertrophic cardiomyopathy to be implanted with an ICD. But probably if we see a lot of scar on a AGE where specific patterns that can help to decide which are the patients that have benefited from an ICD implantation, for example. Dr. Greg Hundley: Thank you. And finally Mark. Dr. N.A. Mark Estes: But I think all the major points have been hit here. And unfortunately we have a bit of a dilemma. And that dilemma is that these legacy trials for ICDs, which selected based on low ejection fraction and functional class II were done at a time when contemporary heart failure treatment was not as good as it currently is pharmacologically. And it's been reflected with a lower total mortality. When the mortality in this patient population gets down to the 4 and 5% per year, it's unlikely that any intervention for prevention of sudden death is going to impact on that total mortality. Dr. N.A. Mark Estes: So I do think that the registries hold a lot of promise, giving us insights into the subgroup of patients that previously would have been selected for defibrillators who may not have as much benefit or who may benefit the most. And I think that they will play an important part in perhaps refining the risk stratification with greater sensitivity and specificity in the patient population, less than 35%. I think the CMR guide trial is going to be a critical trial and looking at ICDs in the patient population between 35 and 50%, but we need to be mindful of one thing. And that in the Danish trial, they get a sub study looking at about 240 patients using LGE. And they found that ICD in patients with LGE that was positive, did not make a difference in survival or total mortality. So again, we need to get the data. I think the best clinical practice has come out of the best clinical evidence. You'll clearly be limitations to what we can do, but I think in the future, we'll have much better data to make these judgment calls. Dr. Greg Hundley: Very good. Well listeners, we want to thank our panelists, Dr. Igor Clem, Pasquale, Santangeli, Victoria Delgado, and Dr. Mark Estes for this wonderful discussion related to magnetic resonance imaging, late gadolinium enhancement, and how it may be useful in identifying those at risk for future arrhythmic events. On behalf of both Carolyn and myself, want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021.  

How are you going to deliver Acute level services in the home?The advancements in devices, models and creative partnerships are leading the way.  Two articles today.FTA 1AliveCor has updated the capabilities of its mobile ECG devices to identify three additional types of heart conditions, the company announced today.Sinus rhythm with supraventricular ectopy (SVE), sinus rhythm with premature ventricular contractions (PVCs) and sinus rhythm with wide QRS are now all on the table of AliveCor's KardiaMobile line of ECG devices, which already detected atrial fibrillation, bradycardia (slow heart rate) and tachycardia (high heart rate).FTA 2"The agreement between Humana and Dispatch Health will provide members living with multiple chronic conditions – such as cellulitis, kidney and urinary tract infections, chronic obstructive pulmonary disease, heart failure and many others – an opportunity to be treated safely at home and thereby avoid hospital visits. Last November, the U.S. Centers for Medicare & Medicaid Services announced a waiver program to allow qualified health care providers to offer acute, hospital-level care in the home. The Dispatch-Humana agreement is believed to be the country's first program to provide hospital-level care involving a national payer.”---What is your strategy to deliver Acute level services in the home?

Today we first take on the complex subject of coaching junior athletes, including everything from building aerobic base in a healthy manner to dealing with overbearing parents.  We tackle a very interesting question on the base/intensity relationship from Danielle in Monument, Colorado: “Does aerobic output after intensity still have the same effect? Or does it have an even bigger effect due to substrate depletion and muscle fiber recruitment change? How does this change how I plan my training rides?” We also discuss how long aerobic rides need to be, based on a question from Ashley in Sherbrooke, Quebec: “How long do aerobic rides need to be to get benefits? And does this change throughout the season, or as I improve as a cyclist from season to season?” Then we turn our attention to this question from Jeff P. on heart arrhythmias: "Do you know if Whoop can ignore or tolerate or take into account premature ventricular contractions? PVCs are pretty common in the population and I started getting them about two years ago. I do get more PVCs when I have more stress but it doesn't seem to have a great correlation with exercise—more so with life stress and caffeine intake." Finally, we address the potential for cumulative effects of supplements, a question from Dan S.: "My question is regarding the nutritional effects of the flavonoids in dark chocolates and the nitrates (?) in beetroot. Are the effects of these type of “supplements” cumulative? In other words, if you do them together do you get a greater buffering effect than taking more of either of them in isolation?" Learn more about your ad choices. Visit megaphone.fm/adchoices

In this week's episode, Dr. Alain Bouchard is joined by Dr. Jose Osorio, director of the electrophysiology lab at the Grandview Medical Center, to discuss the nature of PVCs.About the TeamDr. Alain Bouchard is a clinical cardiologist at Cardiology Specialists of Birmingham, AL. He is a native of Quebec, Canada and trained in Internal Medicine at McGill University in Montreal. He continued as a Research Fellow at the Montreal Heart Institute. He did a clinical cardiology fellowship at the University of California in San Francisco. He joined the faculty at the University of Alabama Birmingham from 1986 to 1990. He worked at CardiologyPC and Baptist Medical Center at Princeton from 1990-2019. He is now part of the Cardiology Specialists of Birmingham at St. Vincent’s Health System, Ascension.Medical DisclaimerThe contents of the MyHeart.net podcast, including as textual content, graphical content, images, and any other content contained in the Podcast (“Content”) are purely for informational purposes. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or heard on the Podcast!If you think you may have a medical emergency, call your doctor or 911 immediately. MyHeart.net does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned on the Podcast. Reliance on any information provided by MyHeart.net, MyHeart.net employees, others appearing on the Podcast at the invitation of MyHeart.net, or other visitors to the Podcast is solely at your own risk.The Podcast and the Content are provided on an “as is” basis.

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.

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Michigan cardiology fellows (Apu Chakrabarti, Jessica Guidi, and Amrish Deshmukh) for some craft brews in Ann Arbor! They discuss a challenging case of Ventricular Septal Rupture after acute MI. Dr. Kim Eagle, editor of ACC.org & host of Eagle's Eye View Podcast, and Dr. Devraj Sukul provide the E-CPR and message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident, Eunice Dugan, with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary - Case media - Case teaching - References D The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A male in his 60s with medical history of obesity and GERD presents with five days of progressive chest pressure radiating to bilateral arms and associated with dyspnea on exertion. Due to worsening chest pain with new lightheadedness, he decided to come to the ED. His presentation to the hospital was delayed due to fear of contracting COVID-19. In the ED, patient was afebrile, blood pressure 96/56, HR 137, RR 22, and oxygen saturation 94% on room air. On exam, he was ill appearing, acutely distressed, and altered. He had a 3/6 mid systolic murmur loudest at L sternal border, JVP to 10 cm H2O and had crackles up to mid-lung fields. His extremities were cool to touch. Labs notable for Cr 1.5, High-Sensitivity Troponin-T up to 5756, and lactate 3.9. EKG showed incomplete RBBB, PVCs, and ST elevations in the inferior leads with depressions in lateral and precordial leads. Coronary Angiography showed mid-RCA occlusion with faint L to right collaterals. He underwent PCI with restoration of TIMI 3 flow. After PCI, he continued to be hypotensive requiring IABP and norepinephrine. PA catheter demonstrated (in mmHg): RA 26, RV 63/29 (31), 55/36 (44), PCWP 29, and CO 5 L/min, CI 2.2, and SVR 467. Shunt run of mixed venous O2 saturation showed: SVC 71%, RA 72%, RV 62%, PA 85% with oxygen step up in the R-sided circuit. Left ventriculogram then confirmed septal rupture with contrast extravasation from LV into RV. Due to worsening shock, he was stabilized on VA ECMO which was complicated by hemolysis and acute renal failure requiring CVVHD. On day 7 after presentation, he underwent surgery which revealed a large 6x6 cm ventricular septal defect on the posterior aspect of the septum and repaired with a large bovine pericardial path. He was eventually discharged after a prolonged stay and repeat TTE on follow up showed biventricular dysfunction and residual 1cm VSD.   Case Media ABCDClick to Enlarge A. ECG: Incomplete RBBB, PVCs, and ST elevations in the inferior leads with depressions in lateral and precordial leads. B. Coronary angiography: mid-RCA occlusion with faint L to right collaterals.C-D.

Ramil Goel M.D., FHRS discusses PVCs and if asymptomatic PVCs are more likely to result in cardiomyopathy. He examines if monomorphic PVCs are easier to ablate and whether PVC ablation is an effective option for patients unwilling to take medications.

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, Jacob Koruth and Associates examine the ability to produce ablation lesions using pulse field ablation, which is tissue specific and non-thermal in swine compared to radio frequency ablation. All 46 targeted veins were successfully isolated on the first attempt in all cohorts. Pulmonary vein isolation durability was assessed in 28 veins, including the SVC. Durability was higher in the pulsed field ablation bipolar group, 18 out of 20 in the bipolar group, 10 out of 18 in the monopolar group, and 3 out of 6 in the radio frequency group. P = 0.002. Transmit morality rates were similar across groups with evidence of nerve damage only with radiofrequency. In our next paper, Vivek Reddy and Associates is part of the multicentered first-in-human study, RADIANCE, examine the ability of a novel compliant radio frequency balloon catheter with 10 irrigated flexible electrodes to simultaneously and independently deliver energy. At four sites, 39 patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation using energy delivery simultaneously from all electrodes up to 30 seconds posteriorly, and 60 seconds anteriorly. 152 of 152 targeted pulmonary veins were isolated. 79.6% with a single application. Electrical reconnection occurred in only 7 out of 150 pulmonary veins or 4.7% upon adenosine isoproterenol challenge. Esophageal temperature was monitored in all patients. The esophagus was also mechanically deviated in ten patients. At three months, imaging revealed no pulmonary vein stenosis and early atrial recurrence occurred in only 10 out of 39 or 25.6% of patients. In our next paper Takeshi Kitamura and Associates examine the effect of substrate based ventricular tachycardia ablation targeting local abnormal ventricular activity on recurrent ventricular fibrillation events in patients with structural heart disease. In a retrospective two center study of a total of 686 patients with incident ventricular tachycardia ablation procedure targeting local abnormal ventricular activity, 21 patients, age 57 years left ventricular ejection fraction 30%, had both ventricular tachycardia and ventricular fibrillation. A total of 80 ventricular fibrillation events were recorded in the ICD logs, the six months preceding ablation. Complete and partial local abnormal ventricular activity elimination was achieved in 11 or 52%, in 10 or 58% of patients respectively. Catheter ablation was associated with a highly significant reduction in ventricular fibrillation recurrences. P less than 0.0001 which were limited to three or 14 patients at six months. The total number of ventricular events therefore, decreased from 80 to three with a median of 1.0 to 0.0 in the six months prior to and following ablation respectively. The reduction in ventricular fibrillation events was significantly greater in patients with catheter ablation compared to 21 match controls during a 6- month period preceding and following a baseline assessment. The authors concluded that substrate guided ventricular tachycardia ablation, targeting local abnormal ventricular activity, may be associated with a significant reduction in recurrent ventricular fibrillation, suggesting that ventricular tachycardia and ventricular fibrillation share overlapping arrhythmogenic substrate in patients with structural heart disease. In our next paper, Feng Hu and Associates examine the effect of right anterior ganglion aided plexi ablation on vagal response during circumferential pulmonary vein isolation. 80 patients with paroxysmal atrial fibrillation who underwent first time ablation were prospectively enrolled and randomly assigned to two groups. Group A (n = 40) circumferential pulmonary vein isolation starting with the right pulmonary veins at the right anterior ganglion plexi site. In group B (n = 40) circumferential pulmonary vein isolation starting with the left pulmonary veins first, and the last ablation site being the right anterior ganglionic plexi site. During circumferential pulmonary vein isolation, the positive vagal response was observed in only one patient in group A, in 25 patients in group B. P less than 0.001. A total of 21 patients with positive vagal response in group B needed temporary ventricular pacing during the procedure, while the only patient with positive vagal response in group A did not need temporary ventricular pacing, P less than 0.001. Compared with baseline basic cycle length, sinus node recovery time, and AV node Wenckebach pacing cycle length were decreased significantly after pulmonary vein isolation procedure in both groups, all P less than 0.05 and without differences between the two groups. In our next paper, Karl-Heinz Kuck and Associates reported the results of the randomized atrial fibrillation management and congestive heart failure with ablation, AMICA trial. Patients with persistent or long standing persistent atrial fibrillation and left ventricular ejection fraction ≤ 35%, were randomly allocated to catheter ablation of atrial fibrillation or best medical therapy. The primary study endpoint was the absolute increase in left ventricular ejection fraction from baseline at one year. Pulmonary vein isolation was the primary ablation approach. Best medical therapy comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter defibrillator or resynchronization therapy defibrillator implanted. This study was terminated early for futility of 140 patients, 65 years, 90% men available for endpoint analysis, 68 and 72 patients were assigned to ablation in best medical therapy respectively. At one year, left ventricular ejection fraction had increased in ablation patients by 8.8% and in medical therapy by 7.3%, P = 0.36. Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year. In 61 of 83 ablation patients, or 73.5%, and 42 out of 82 best medical therapy patients or 50%. Device-recorded atrial fibrillation at one year, was 0% or maximally 50% of the time in 28 of 39 ablation patients, so 72% in 16 out of 36 best medical therapy patients or 44%. There were no differences in secondary endpoint outcomes of six-minute walk tests, quality of life or NT pro BNP between the ablation and best medical therapy patients. In our next paper, Dhanunjaya Lakkireddy and Associates examined the association between unrecognized inflammation and premature ventricular contraction. In a single-center prospective study, 107 patients with 5,000 or more PVCs per 24 hours, which were symptomatic, and no known ischemic heart disease, underwent combination of laboratory testing including FDG or 18F-fluorodeoxyglucose pet scan, cardiac magnetic resonance imaging, and biopsy. The mean age cohort was 57 years, 41% were males, a left ventricular ejection fraction was 47%. Positive pet scan was seen in 51%, and 51% had preserved left ventricular function. Based on clinical profile, FDG pet imaging, cardiac magnetic resonance imaging, and histological data, 58% received immunosuppressive therapy alone and 25% received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% over a mean follow-up of six months in patients with left ventricular systolic dysfunction, 37% showed a mean improvement in left ventricular ejection fraction of 13%. In our next paper, Clare Atzema and Associates examined the association of rapid (3 days), early (7 days), and basic (30 days), outpatient physician follow-up with short and long-term outcomes in atrial fibrillation patients discharged from an emergency department. In 163 emergency departments in Ontario, Canada with a diagnosis of atrial fibrillation, they use landmark analysis with propensity score matching. In the 10,657 patients with rapid follow-up care who are propensity score matched to a patient with follow-up between 4 and 7 days, the hazard of a return emergency visit was reduced by 11%. In the 17,234 patients with early follow-up who are matched to a patient with care between 8 and 30 days, the 1-year mortality was 11% lower, and 1-year hospitalization was 6% lower. Relative to no 30-day care, basic follow-up care was associated with an increased hazard ratio of 90-day hospitalization, but no longer was associated with mortality. The authors concluded that compared to follow-up care between 8 and 30 days, follow-up care within a week after discharge from an emergency department with atrial fibrillation, was associated with a reduction in death, in hospitalization at 1 year, in association not present with 30-day follow-up. In our next paper, James Freeman and Associates evaluate outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding hospitalization in patients undergoing atrial fibrillation ablation compared with a propensity score match cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) I and II registries. Among 21,595 patients, 6% underwent de novo atrial fibrillation ablation. The propensity score matched cohort included 1087 patients who underwent atrial fibrillation matched one-to-one with 1087 patients treated with an antiarrhythmic medication only. There were no significant differences in the risk of all-cause and cardiovascular death in most other major cardiovascular and neurologic events. Atrial fibrillation catheter ablation was associated with an increased risk of all cause hospitalization hazard ratio 1.24 particularly in the 3 months after the procedure. Among those who underwent atrial relation ablation with CHA2DS2 VAS score, 2 for men and 3 for women, 23% had oral anticoagulation discontinued after ablation. Among those with discontinue oral anticoagulation, the median time to discontinuation was 6.2 months. Thus, the authors found no difference in adjusted rates of cardiovascular and all-cause death, between patients treated with atrial fibrillation catheter ablation and antiarrhythmic medications only. In our next paper, Michael Liu and Associates examined R-from-T as a common mechanism of arrhythmia initiation in long QT syndrome. In their study, spontaneous initiation of polymorphic ventricular tachycardia was elicited by gradually ramping up ICa,L to simulate the early phase of sympathetic surge or changing the heart rate, reproducing the different genotype-dependent clinical electrocardiographic features in LQTS type 2 and 3, T-wave alternans was observed followed by premature ventricular complexes. Compensatory pauses occurred resulting in short-long sequences, as ICa,L increased further polymorphic ventricular tachycardia episodes occurred, always proceeded by short-long-short sequences. However, in LQTS type 1 once a PVC occurred, it almost immediately led to an episode of polymorphic ventricular tachycardia. Arrhythmias in LQT2 and 3 were bradycardia dependent, whereas LQT1 was not. In all 3 genotypes, PVCs always originated spontaneously from the steep repolarization gradient region and manifested on ECG as R-on-T. the authors called this mechanism R-on-T to distinguish it from the classic explanation of R-on-T arrhythmogenesis when an exogenous PVC coincidentally encounters a repolarization region. In R-from-T, the PVC and the T wave are causally related, where the steep repolarization gradients combine with enhanced ICa,L leading to the PVCs emerging from the T wave. Since enhanced ICa,L  was required for R-from-T to occur, suppressing window ICa,L  effectively prevented arrhythmias in all 3 genotypes. In our next paper, Dhani Dharmaprani and Associates hypothesized phase singularity formation and destruction in fibrillation could be modeled as a self-regenerating Poisson renewal processes, producing exponential distributions of inter event times governed by constant rate parameters defined by prevailing properties of each system. The authors studied 5 systems, human persistent atrial fibrillation in 20 cases, tachypaced atrial fibrillation in sheep in 5 cases, rat atrial fibrillation in 4 cases, and rat ventricular fibrillation in 11 cases, as well as computer simulated fibrillation. Phase singularity time to event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of phase singularity formation and destruction were determined. A systematic review is conducted to cross validate with sources from the literature. In all systems phase singularity lifetime and inter formation times were consistent with underlying Poisson renewal processes. The authors conclude that Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation. In our issue, there was a very interesting special report on hypothermia outcomes after transvenous lead extraction complications requiring cardiothoracic surgery by Peter Hu and Associates. In addition, there is a very interesting review of atrial fibrillation mediated cardiomyopathy by Kevin Heist and Associates. 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.  

In this episode of the Heart podcast, Digital Media Editor, Dr James Rudd, is joined by Dr Marc Deyell from the University of British Columbia. They discuss his Heart paper "Outcomes of untreated frequent premature ventricular complexes with normal left ventricular function" and how it might influence practice. If you enjoy the show, please subscribe to the podcast to get episodes automatically downloaded to your phone and computer. Also, please consider leaving us a review at https://itunes.apple.com/gb/podcast/heart-podcast/id445358212?mt=2 Link to published paper: https://heart.bmj.com/content/105/18/1408 https://heart.bmj.com/content/105/18/1386

PVCs

Cooper Read is a GREAT storyteller while his career journey includes playing college baseball, a surgical technician, an adventurer and journeyman, MAPS & Zendo Project Advocate.Cooper has tells how he found inspiration knowing that he wanted more out of life than what the health care industry could provide in traditional institutions. Also, a mention from Ken & Eric about how you cannot out exercise a sedentary lifestyle and a customer story about CBD and vagal mediated atrial fibrillation. Instagram: @cooper_readhttps://maps.orghttps://zendoproject.org/https://lovemytummy.com/spoonyhttps://kbmdhealth.comInfluencing I think during Re: did you want to stuck in a bad bundle get a great bundle AT&T vibrant DirecTV and get $100 reward card requires 24 month TV 12 month Internet agreement redemption required limited availability may not be in your area if you qualify.com/bundle AT&T that are subject to change new customers requires a minimum 49 and nine month 12 months after the price hiring secular Internet 25 minutes or higher minimum $40 a month early termination of return taxes fees and restrictions apply, visit.com for full details and it is now time for the gut check project you were here with your host Ken Brown MD I'm Eric Rager this is where you check your ego at the door because nothing got the table Doug can you do it for the person or the few times it is my title there MD so I'm here with my co-third-grader cRNA like that mix it up as you can tell I will do it different almost every single will episode 14 at what we are on episode number 14 that is correct so today we got a really cool desk alone and I'm super excited about this sort of things that you what I have done we get a lot of feedback from people that are been writing in is that we bring just on that were try to learn some stuff from correct and I think that almost everything will episode I become more knowledgeable it is expanded my mind I think today is exactly where we need to be because we have somebody who's a great storyteller that's got some incredible experiences just throws himself out there that's kind of a sort of how work, doing everything right now and if you're new to the gut check project I think it would you find that what can I both want to do out of the guest is find a little bit about their journey that took them to where they are now because life is a journey to find that you you're going to be satisfied once you know more about yourself and how you know what you want until you have exploded morality so exactly so work we have Cooper read on the show today and he is somebody who is really it's a lightning she actually inspires me and other people around him and he just jumps and of to explore different areas different ways of health and easily get into a lot of different stuff but if you're somebody who's kind of stuck in a rut right now this is your show converted to cover novel French stuff that I think is actually something that can change both health and mind yeah absolutely happy at think that Cooper has a great story of just being dissatisfied is where he found himself and decided to do something about it so allowable I'm not going to ruin his story that will get to that whenever he joins us here about just so happens that is doing something about it in a field that I have tremendous interest in and medicine is going that way and I think that we will all be talking about this five years from now as how really to improve mental health without question without question real quick of course if you also knew to get project and even if you aren't should always go to love my tummy.com/spoony where on the spoony network so/Bernie will give you are trying to heal outrun teal at a discount that you won't find hardly anywhere else so what is that all 20 oh that makes it so unique to Brown so this is kind of exciting this is my baby right here in a little shout out to Siobhan Sarna who is the head of the IBS SEBO SOS summit because probably much to her relief I finally got done filming my webinar for the experts on that is so nice and we got a chance to one of the reasons why I was looking at the other of future lectures and she's like you're the last one to do this of Mark Pimentel the psyche shroud it is we've got to know Tom Osborne that that is all these other people and Allison C Becker she's like you're holding up the whole show they yell for those who are into keeping the health and follow us and get the emails that we get every week that we send out just be sure and tune in because what Dr. Brown is referencing is see below SOS some and if you've ever been interested in why certain people suffer from G.I. distress and they can't quite find the answers that's kinda what this whole summit is about not everything is going to apply to everyone but there may be something in there for everybody who tunes in supercool about this particular summit and what Siobhan is put together is that you have people that have had different experiences doing different things right and my experience was in trying to find a natural solution for people with reputable bowel syndrome bloating change in bowel habits and that's how we discovered trying to with two trials which have been published and we been out now for about three years and the reality is worse in the same clinical results that we did in those trials which is 4 to 5 people to get better if you have the classic symptoms of when you meet you blokes now the other cool thing since we launched is that we have since learned through other scientists contacting us that the polyphenols in front your action extremely beneficial for you they work on an antiaging level there's data to show that you are living goes up which helps get rid of old and aging cells this data to show that you increase nitric oxide to the muscles so if you're an athlete so it's really exciting I started this journey to try and help people that were bloated that have bacterial overgrowth and we just keep expanding and knocking down your doors and that's what's so exciting about this I'll try to love my tummy.com/spoony putting code spooning SP 00 and why and you can also experience the so this is my baby show little support at least cash in one coupon that's that's your mission I want everyone to commit to cash in one coupon so that I know that people are at least realizing the importance of both gut health and overall health threat on the battery cell five for a friend or family member that may separate from my G.I. issues so I of course got check project like and share like and share like and share thank you for all of the new subscriptions we reached out to our KB MD health community for the first time this last week to introduce to them the contest where we are giving away to at least five winners the signature protection package of arch on tail whether it be with community CBD natural flavor or sentiment and keep those submissions coming get a friend get a family member to do the same for you like and subscribe to get to project either on YouTube or on iTunes choose an email through going to KB MD.com Sino community health.com and you click on contact sheet is an email it's easy that's all you have to do sign up and then in July we will be drawing at least five winners so the public to be more solid and make you kick the science this time why do you call that the signature package what do those two things blend so well together CBD and affronted absolutely no great thing that you're doing with CVD is that everything that you put behind this and this and I'm in if you're listening through the audio only I picked up both the CBD and the John Teal you have real cases that have come through the clinic and was shown improvement so using this combination is what you found to be the most predictable I guess solution for people who had some type of inflammatory issue and I won't go through all the different disease states but essentially combining the CBD with our Tron tale is the polyphenols and allow the CBD to even work better how does a Duke well there's a little enzyme in there that Decker dates are endogenous CBR cannabinoids like Ananda might for instance name FAH and good polyphenol intake actually prevents FAH from becoming overactive in eliminating the CBD from working were supposed to work exactly and so you're taking a science today but that's on, called the signature package they each make each other better and that's how come we teamed up to have the KB MD health CBD powered by Alexa absolutely so likes it like a chair guy got check project thank you for all the new subscriptions as last week that is that is amazing they tell us it would take at least 20 shows and were doing about episode 14 so we certainly appreciate it so now in a move into Dr. Brown what you have on the news topic for today well so on this topic first of all you couple quick shout out side I am horrible with time zones and we were going to have a fantastic Dr. Dr. Gabrielle Lyons she's a medical doctor in Manhattan she is a fitness expert muscle centric protein expert she did her graduate studies looking at protein she was in a call in and where to talk about peptides because that's my article to talk about little bit later peptides and unfortunately she text eventually gritty role in like oh time zone difference forgot about that and so she is a doctor so we couldn't get her to the work you have her own prolonged show trip organizer bring her here or would you be able to do it she's I think due to have a baby pretty soon so I don't want to have a new mom flying around like that which probably zoom her and but she's super smart and the reason why bring up is because we had one of our listeners asked something and this is right in Dr. Lyons were real house I was a said Trisha's email Tricia called in and said hey can you recommend a Kazen free protein powder now coming up soon in a week or two were to have another fitness expert named Max Fairchild she is super smart peptide expert he formulates nutritional products he's really the one answer that question Chris were to get that to you right away I can look it up but honestly go with the people that have already done the homework they've Artie tested it is the people that have looked at all the formulations were to find the best one for you so keep those questions, and it absolutely and did you have anything to add to video shot you on awesome podcast that just aired early this week I was I was on the intermittent fasting podcast with Melanie Avalon and Jim Stevens I think this is the second or third time a bit on their going on the dance anytime I think yes and yet the second time it's great we talk about fasting the lot more than fast we talked about fasting the medic diets we talk about all kinds of different things and I thought it was a great show and shout out to Melanie she's got a new podcast and I would be going on that on the well go one of the 24th I don't know when should you publish it but she's got so she has a hold of the podcast but that was really cool check it out intermittent fasting podcast and you can hear that episode and we talk a little bit more than just fasting it's those are two really smart people very very fun people talked about that's awesome I did want to bring something up to you I was reading a blog article from Chris Kuester here recently in a reminded me somebody member a little over a year ago there was this new message was being pushed out talking about sitting is the new smoking that's right so never talk about a sedentary lifestyle will if you remember it wasn't that long ago did tell you and I, laugh there's a lot of truth behind what you eat oftentimes you can't necessarily out exercise and what was that someone said you can't outrun the fork you can't outrun the fort that was it that's a shout out to somebody that we do have have in the show at some sometime the name Todd Smith is a bodybuilder trainer out of Omaha Nebraska he'll supplement stores and I heard him say that once like I am still sure what is is a lot of truth to that you know if you want to be healthy a lot of it comes to aware which of your food fuel source is is it healthy for you and what is that translate to so what Kuester was able to illustrate quite well is that if you're sitting for long periods of time throughout the day he can't really out exercise the damage that you're doing by sitting for this law say that again so so and this came in a blog from Chris Chris are who we know well and was your oven is great guy he wrote a blog all about sitting then yes he did any reference to a handful of studies he basically put together he does a great job of always aggregating different things that he's reading pulling great information making easy prey to can I consume but essentially showed that even marathon runners when they're not actively training is another there's other issues that may be going on with marathon running of long-term inflammation exposure anyhow but that aside there actually at more risk according to some of these articles he has and therefore coronary artery disease because of the long periods of times it they're not training and that are not running the marathon site are sedentary and that actually affects their metabolic rate from sitting so then you begin to die little bit deeper looking into sitting while working if you go to in office and you don't engineer of engagement your computer and your having to type for long periods of time you're still sitting obviously you're working you're working hard but possibly examine what would it take for me to get a standing desk or something similar that would give you some variability in fact Robert Hendrickson has a a new a new product that easily come out with rover that we had on from full bucket health that's right after the show he was sure the silver color prototype to have some sort of portable version of that so that you can get away from just sitting all the time you admits it's brilliant anyway it solves a lot of problems of course it gives you a portable office that you want to go but at the same time you now have the availability to not be confined to sitting while taking care of work will essentially what Christer pointed out is sitting for 11 to 13 hours a day and many people may say when I don't do that I get more than that and you may think that but you drive to work and then you put in 6 to 8 hours of sitting you wake up you set out have a cup of coffee and follow up on whatever it is you do you come home drive to work you may work out but that is a matter because they can sit down to eat when you sit frequently and then you sit down to attitude to maybe watch program at home before you go to bed that amount of sedentary non-movement over time as an aggregate the you simply can't out out exercise according to the studies well it's interesting because if you sit for more than six hours it's been shown that your lipoprotein lipase actually goes down and that's what burns fat you can actually have a decrease in your bone mineral density leading to osteoporosis and then ultimately increased coronary events due to high blood pressure and coronary artery disease than when you stop and think about it sitting is not very good. And if you look at how we evolved we really didn't do a whole lot acidic we were always on the move around so let's come up with some ideas right now we want everybody to at least try for the next week to sit there and do the so when you're put a timer on your desk chair or timer on your desk I think about it you can elevate your desk a little bit that there's all kinds of different options out there for you to do it what if you if your teacher if your teacher and you feel like that you are engaging the students on a particular subject maybe change the scenery have a walking meeting don't take the elevator if you can take some stairs what else oh I was just thinking that the first for the whole teaching thing to remember the meeting that we are at in Utah with the bathwater, and one of the moderators before they even began made everybody stand up and shout around guess I just get energy upright just get everybody moving and then that's how she said she starts all her podcast like that she makes her guess do that just to get them up and ready which is really cool so anytime you get up and do that I think that elevating your – we walked Wenatchee had a patient from Veritas the big company that does this trip we walked around my office and looked at different ways different deaths we can do for the employees last of it with this be something you would like and they were all unanimously really interested in that unlike Robo was talking about he thought that would be really difficult the beginning but suddenly he's standing for eight hours doing all his work no big deal at all none at this temperature and it don't you find it days it weaned up having to pound away a lot of computer work compared to the days were doing a lot of scopes are you doing a lot of clinic visits I have more energy after doing all the movement throughout the day than I do when I'm what's up once a month twice a month I just have to kind of pound a lot of work on the computer those of the most draining dates to me in it and I really didn't move I just sitting there panning out on the computer and its signage oil will melt let's just throw one other thing in there so people sit that they sit all day than they come home dad and then they get on their computer the blue light now your jacket up your circadian rhythm and I mean where really try to kill ourselves and like everything that we do in life right now is basically shortening our arches our health time is really what it's doing we have this were doing those other things to try to correct it but these are all easy life hacks that we can do get out wake up one of the greatest depending what time you wake up wake up really early so the sun is out for the greatest things you can do to turn your circadian rhythm is get up go for a walk on an empty stomach with sunlight to convert the vitamin D you turn on your circadian rhythm you're telling your brain were going to do this and it does a couple quick things number one you get your body movement to get out you little sunlight and you not waking up and immediately sitting down which is what a lot of people do and you know what I'm I try to do this I wake up every morning really early and I make my coffee in the French press and I got my little routine habit or routine is pretty important if you like a lot of people like Tony Robbins of the people to say Arnold Schwarzenegger like really highly effective people they'll have a very specific morning routine chair Tim Ferris Joe Rogan all that I will sit there and start regular coffee then work on the charts I took it one step further and I got a vibration plate I tried to stand on it and I should do my truck; unpacking this setting was it turns out it's really hard to do computer work with vision vibrating (32 oscillations per second or whatever so you have noticed in those vibration plates are kinda interesting but if you lock your knees out man at that there really affects model skinny legs I just take the population straight up to my eyeballs I can't hardly see much anything that so just simple access something that will go talk about in the next half-hour is going to be a another hack I was listening to one of the greatest biomarkers of all time Ben Greenfield, he talks about migration place he talks about getting out or talks about the get some sun they were talking about peptides which is really what I wanted to have Max Fairchild on in his you come back on here in a few weeks to talk about peptides and that is another little hat these are all things you can do that aren't that not that difficult to really make a big difference in your life and offset some of the stuff so fierce that they're stuck in traffic or if your sit in your cube: every time you stand up your bosses sitdown or your student teacher says sitdown there's ways to get around it just make sure that when you have it under control you can do all kinds of stuff were going to be talking with Cooper about different ways to engage with nature also data that's another little way to get your brain stimulated to get your circadian rhythm and track and all that definitely ending of these these are things that if you're a member of KB MD health here pretty soon Dr. Brown his mood coming up of the system where we can start putting together some of these small tips that were finding out basically just amassing these studies and how you can take these into practical life managers hearing this morning I work at XYZ I understand it's tough it's up to make a change what we want to do is see if we can help people find easy modifiers to make those changes meaningful to you and a little teaser may be have it delivered straight or maybe have it delivered straight to your home is by building a news coming out about that over the weekend so if you are on KPMG health.com and they are member of KPMG health look this site no later than the Sunday maybe before but probably no later than the Senate would get a really really really cool announcement on something you been working on for well over a year well over a year with some really smart people out there shout out to Mr. Zell of course but there I want to make a difference in my community sure and I think this is a way to do it and I'm really excited to start implementing some leasing's meeting other experts do all kinds of stuff and you would be Sony and if you're not a member of KPMG health aide cost nothing you said to go to KPMG health.com Pan down on the button on the poorly designed website that basically have no about myself and about we are working to prove it we brought in and we have an intern in Internet started this week we have someone who's actually going to help us do stuff thank goodness yes thank goodness that read had to find somebody that's like half our age to do that I am super excited to have someone help us get those things done and he sees already off and running in and helping as the redesign so that will be great speaking which I need to address something you know that the processor is you write yes so several of you and by several I mean a few hundred of you have not have had issues while trying to make purchases through the website on KB MD health and it is truly no fault of ours it's two healthcare people try to run a website but the processor since we do process CBD sales all of the banks collectively have basically come up with new parameters that you have to be vetted and you have to have a right processor they're basically trying to prevent fraud so for every reputable business is about 20 they just aren't there try to weed them out so we're it it's it's inconvenient for us but were were getting through it and I've been kinda forced to handle it in the evening some phone calls from some folks so that we can do some manual transactions not a big deal though and not all bad has come out of it I've met some great people some great supporters some people just have questions knowing you like I could totally see you know it's not bad in fact I'm been invited to several weddings and onto a vacation with whatever whomever they are but I did get interesting call I guess it was three days ago from a Jonah from South Carolina and he's been watching the show because his daughter who lives in Houston found found the gut check projects weight and they been sharing it back and forth they like the episodes well he's now customer of KPD health CBD but he wanted to tell me specifically about what CBD was doing for him and on a moment to full depth on this with you but vagal mediated PVCs that was basically where he was coming from he said that his vagus nerve in his interpretation of it was that over vagal stimulation in even even in that I I'm still trying to wrap my head around it but would elicit PVCs and throw him into a fit and post and say the vagus nerve is a exquisitely complex thing that runs from the brain all the way down so were to have a vagus nerve expert what outpatients that's his work as a PhD he's working at vagus nerve stimulation and what it does and where can go so we can that's good that's a whole separate episode but I love the fact that he called and why do you think the CBD helped him I don't else really good question his his interpretation was that something with the vagus nerve whenever it wasn't performing properly he could have PVCs and throwing himself into a fit but something that he'd found out is that using high quality revocable CBD dose actually prevented him from having a fib episode taken last summer between 812 hours 28. Go in a fit anymore and he had the same experience so far with KB the CBD which I thought was great in a course is anecdotal's are not making a claim but this is what he's found utilizing that he's been in in conversation with his with his cardiologist to talk about that but all that aside I would like to dig in deep with within the course the vagus nerve is it's think that Vegas is Latin for wanderer it's a nerve it is the peer sympathetic nerve is a great regularly because all way down and regulate your gut as well and it's interesting because even in the SEBO form committees and things people really try and make some sense of it they try and figure out how to manipulate the vagus nerve words can bring one of the world's experts on church to do a deep dive real geeky scientific dive into it to make sure that your vagus nerve is hopefully the beauty of CBD it works I can adapt to gents which credit goes where you need yellow you get the faster time goes by that because that's another half hour so episode 14 will be back here after the break with Cooper read in just a moment why have thousands of aspiring authors teamed up with Christian faith publishing to publish their blog because Christian faith publishing is an author friendly publisher who understands that your labor is more than just a book we provide authors freedom and flexibility throughout the publishing process professional book editing award-winning design and some of the highest royalty structures in the publishing industry and is always you will retain 100% of the rights to your book I was looking to find a company that I could trust one that assisted in the editing process completely Christian trade publishing will publish market and sell your books in all major bookstores and online booksellers as well especially Christian bookstores call for your free author submission kit 800-978-4812 800-978-4812 800-978-4812 that's 800-978-4812 never forgotten apparel is more than just a premium women's and men's clothing line it's a movement to remind us to where American-made and serve those who serve us our heroes never forgotten apparel gives 20% of their total sales to nonprofits that support homeless veterans and off-duty firefighters and 50% to individual veterans and firefighters in need nationwide checkout never forgotten apparel.com use promo code Matt and ATT and get 15% off your purchase Dr. Kim Brown here host of project with my cohost Eric Rieger I've seen in my practice that I tried to as a whole lot more than just the bloating product yes it does a whole lot more than just exploding because the polyphenols if you find in Alicante what are some of things these polyphenols do affect these polyphenols can help you have more energy and polyphenols are great it sounds like it's good health: more people than just loading go to let my Tommy.com/and we are now back for the second half hour episode 14 gut check project I am now joined on my ride by Mr. Cooper read digital entrepreneur and social engineer Adaline Cooper doing very well guys I'm happy to be here so you're also a maps advocate as well as the fun I'm going to screw the name of Zenda project I volunteer correct absolutely as in the project and maps organization the multidisciplinary Association for psychedelic studies you have an advocate for that can push that but I really am a volunteer present no projects yet what is what is on the project and the project is a project it's underneath the maps organization they set up the arts in music festivals all around the world and again hold space for people that are having difficult psychedelic experiences that have story after story was the reason why want to have you on so bad is because I really do we we've actually interviewed Dennis McKenna who is a godfather in psilocybin there are in my world there are no FDA studies going on with her looking at suicide but for different things and were to jump right into your history as soon as I countertop but we always try doing the shows at least we get through one academic paper to get everybody up to speed at least on something try to teach something so there just yesterday the US news to know the report where it showed that US death rates from suicide alcohol and drug overdose is reached an all-time high so I think there is no better time for somebody like you being involved with the maps to start integrating some of the stuff because were clearly not doing a very good job were committed suicide more often were dying from opioids and all this so what I wanted to get into on the fringe a little bit is something called peptides so I am not an expert in peptides of Max Fairchild is Gabriel aligned Debbie alliances that we were talking about but so I try to teach myself a little bit about this and so I found an article on a peptide called BPC 157 soap BPC 157 is a peptide chain consisting of 15 amino acid so peptides are just very specific amino acid and Ben Granger was talking that when does a peptide become a pro to Mauritania yet and if there's there's really do know the experts on this can say well it gets really weird because growth hormone is still considered a peptide but it's really that it's a really big peptide so that it's just very specific amino acids put together so BPC 157 although it's considered synthetic it's actually a protective protein which is found in the stomach and it's known for its anti-ulcer effects of the known about that for quite a while Dr. Lyons is the one who told me to start using my guest wrote you practice I'd never even heard of it nobody ever talked about that so I'm super excited that I'm now getting into this aspect so researchers are conducted numerous rodent studies that show that it doesn't protect against of protective effects but it also seems to extend beyond the stomach and intestinal tract so BPC 157 has been shown to benefit ulcer healing the stomach intestinal damage such as fistulas and inflammatory disorders but there is some anecdotal evidence to show that bone and joint healing also takes place what I really wanted to get into is in my practice I talked about the brain got access all the time so I found an article researchers out of Croatia have done rodent studies looking at the influences on the brain got access and this actually comes from 2016 and what they did is they looked at DPC 157 and over a very long period of time they tried to show how not only is it protective in the stomach but it is very useful as a peptide in other areas of the body specifically the brain is funny because their thought on this was the first auditing to think about this when we top of the brain got access in the first one actually show that was Pavlov I have lobby and respond Escher fistula in the dog ring a bell here's it turns on the intestines that's a brain gut response yet is so we all have this and so the main thing that BPC 157 does it is a growth like peptide so it turns on genes that increase blood vessel growth and nerve growth since we were taught to draw ever is if you're like me going what BPC 157 turns on blood vessel growth and nerve growth while that's while it has wild so wild so what they did as they looked at a bunch of different well brain mood issues and I specifically looked at these animals and so how does BPC 157 help with this/want to go through in the articles really Berrigan charity coupons along so I try to go through a few things because if you suffer from any one of these but start talking some peptides okay depression they proved that BPC 157 actually acts on the dopaminergic and serotonergic systems as well as the GABA system member a few episodes back we talked about how CBD can directly bind to serotonin right much like an adaptive gent it's almost like this is adapted and also they show that in these animals they induced depression and I don't I really get into how they actually do this with the animals on and off they served with divorce papers nudging winter jobs only or that you like the big firearm then whatever it something you know I can't sit down for too long so actually induced depression measured all these different levels and they showed that serotonin and open dopamine and GABA all came back to normal levels after being injected with interesting 57 okay super well, this will alcohol withdrawal they showed that it actually counteracted acute and chronic withdrawal as well as healing the liver and the G.I. tract that is very interesting but it makes a lot of sense on why people can't escape alcoholism oh one step further opioid withdrawal allow just kept on saying you with death rates from suicides alcohol drug overdose will result in high and what you're going to talk about as some psychedelics have some great promise I'm learning about this for the first time and I'm reading this albeit animal models but it's very hard to get FDA to approve human studies we know that so there has to start with animal models sure it showed that the opioid receptors would be down regulated after getting it so that they didn't have that yearning with her like demanding the opioids that's that's actually really impressive then it gets into disease states multiple sclerosis BPC 157 effectively counteract the development of brain lesions and MS induced mice traumatic brain injury they actually stimulated nerve growth and decreased brain edema after inducing try to bring injury spinal cord injuries it improved rat tail movement after the end because a spinal cord injury so basically this is what I really consider a true life hack if it difficult this can be put over that's what I want to have his peptide experts on so I have not use the personally I've not given it to my patients yet to them just discovering this but when we start combining these different things sure it's a natural immediate well it's a synthetic amino acid sequence but these peptides the really big in the bodybuilding community the really big and antiaging community which sometimes I've always said that I felt like endurance athletes and bodybuilders know more about nutrition than any gastroenterologist they manipulate the body through sure so what we talk about here and you're going to carry the torch now because what we talked about is some pretty cool stuff like we've covered stem cells CBD photo bio modulation these are all easy to implement things that can make a huge difference in your life so I was looking at the star some Facebook groups that are that are really proponents of peptides and I will set a couple emails on that question to have no like right now whenever for Max and just for us to come to think about something that we have the answer specifically from the research that that we have I know before Shire for 157 but what makes it synthetic and is there a is there a natural counterpart that that does that and the other one would be with all of the the advances are the disease states that we talked about would benefit from what about peripheral diabetic neuropathy if you're talking about our generation and blood flow in an angiogenesis or growth of blood vessels and that's that's ultimately what ends up you got get there poor guys got diabetic neuropathy in his feet and he is sitting too close to floor heater and burns off the ends of ends of his toes he can feel it or or starts taking Lyra cover gabapentin or something and you know all those commercials yeah cause depression above the head falls off to me all those things so what makes it synthetic I did I had to look this up on examine.com it's considered a 50 amino acid sequence it's only considered synthetic because the particular sequence has not been extracted be in the exact sequence it's probably believed to be a large one that gets cleaved that works on the side of protective area of the of the stomach so it's only synthetic because they've not been able to actually extract it in the exact same sequence from a human possible that it lives somewhere even if it only for a brief period of time we do seven found in its whole form yet exactly it's like many things that you know you can either I've had this I've had this discussion with different pharmaceutical companies where when you look at that will say oh it doesn't get absorbed with the be like systemic effects in the argument from the pharmaceutical company is owner but when you take our drug you won't see this in the blood in my argument is when you eat a steak yes he stake in the blood yeah right you break down ESU and amino acid complex and that's that's that's one of the things actually happens to do pharmacokinetic studies they say oh take this is it in your blood doesn't get absorbed okay white why my feet swelling wide what are right I heard or whatever you that since the whole prodrug to active component thing you know it's basely taken in this hold this this is and what's going to the action it's when it's broken down or assembled into something else that is in the doing whatever it is yeah totally so BPC 157 were to learn more about it and when we do have a real expert on about that I'm just can eat his brain and just or her right however the expert is not only messy that's just some work I just subscribe for shares are welcome to gut check the project's mess so speaking messes I don't know while that is even a good segue really at all so I think that we should go ahead and not reconnoiter here and go read and reread and reintroduce Cooper Cooper read I like he said he is a digital and social entrepreneur now that you found use your way there in a completely different career path and where we probably may have crossed paths early before didn't but didn't really get to know each other right right absolutely no born here in Texas I was born here in Texas small town grew up in Paradise Texas tiny little you know I know there's a dot for paradise but it's out of nowhere here in North Texas and then now what where did you find yourself after you are you left. I yeah so died I felt paradise when traveling around for you know I get a plate a year of college baseball Texas Boston University in the know then I went in the Denton and got really to the arts after my baseball careers have over from there I decided I wanted to go into performing arts so went to Dallas got a degree performing arts and from there I got opportunity rip Chicago studying commie and no second city in the improv Olympic up there just to show talking about your your life is one of the comedy cards like you to say offensive stuff and just blame it on the company joined the professional comedy Association it's much easier to get into the actors Guild yeah yes I like what if about you to the cards always want to do it whenever I offend anybody absorb what you say yeah right as it I don't mean it this material anyways and from there I became a father and came back to Texas and had to get a real job and quit bartending in and doing comedy stuff on the weekends got into the surgery technology that assert became certified surgical tech and started my career in Denton and then moved to back home in Wise County Decatur Texas and wise region there specializing in euro spines in Branson orthopedics will you that orthopedic so you know he worked with one of our former guess right would that be Dr. Wade McKenna yes Ashley work in Canada several cases it had II have a very just so many fond memories working with that guy he so good so talented what he does in and then his you to ongoing research and education for himself and just what he does is just awesome I'm a big fan Dwight McCann I like to give them a shout out some point and say hello where he says hi you were actually huge fans also when it when he came on the show I thought that was one of the coolest if you have a chance look at that episode whatever number whatever number that stem cell self there is something that you did look at did you ever do it who did you assist him in any stem cells are to do only just do the open cutting stage and open cutting staff you know and then he would get in and then you'd spin the plasmon stuff in and re-administer that no one's closing was done to help with the healing and think that you know like that after he was doing that in the MLR PRP experiments to hear he had his own centrifuging at using one or two dedicated people there they were just there is basically a mini lab and rail are right in the middle of the signing Alec while we were doing the casing I would be spinning that the PRP and separating all that and then at the end of it it was a know what the assist job or whoever was helping in a close up the case they would administer that for a for you know the healing process and regeneration goes on that is really cool why Nancy was into any course she had added to awesome ortho's there have chronic and repair of the asset I spent lots of time working with Dr. Barrow he's these were my favorite surgeons is a great great position and a great guy and generally you know just anyways those guys and in his first assist is her sister Jacob has been with him many many years is one of my best friends and and I super sharp guy and also super fun and really get another college baseball player yeah yeah so it sounds you had a great environment right there did something happen what you dislike said screw this through down the live trocar or whatever it is take off and walked out or what happened so I really I wasn't I wasn't happy or fulfilled after certain amount of time you know I like I said I was in Chicago studying calmly all the stuff and then I was like okay what I get a real job raise a family do that sort of thing so Jacob Mayberry invited me Dino to his okay maybe should come check it now follow Romero and I in the case and see if you want to go get certifies of something you want to do and so I did that audited today with Barrett Ruth Rivero at Bridgeport and then from there is like a family survive and do this for a while and then you know several years ago I know that for five years and I start to just kind of check in with myself and realize that I'm not not happy now at my home life I'm looking back on now might be a little bit of depression you know I had all these great things going on had a good job is in a happy I like the people I was working with but you know there was just I was tired. He didn't have a creative outlet I didn't have that outlet now you did know if you do the performing arts than comedy you've got that brain that needs to constantly be stimulated like that right right and so when in surgery became so monotonous so robotically you know do insane things and you know I I rose up to be no really good you know in the in the spine and euro area and then and even that you know everyone like I'm helping people you know it's fine brains working on that and that's awesome that's exciting I love it but after a while I just knew that I did what I wanted like my heart was call me to like be out and about and go moving shaking and then but as my my health started deteriorating as well with liquid like to the 50 and that the depression and asked her to gain weight and really was the unhappiness with the way in all not really unhappiness with the way but just like the not being fulfilled and being unhappy plus the weight gain had every check in with myself and figure out what was going on there so start taking steps to get healthy so let's look at that what how you think that you ended up becoming unhealthy in that environment because unfortunately we see a lot of people in healthcare and I think there's a lot of reasons for the hours stress the shift work all different cards think so our healthcare providers sometimes are sacrificing themselves without even realizing it to try to help other people how do you think that process happened with you I'd I mean I agree I think that's what it was he knocked the long hours the unit with its physical work here on your feet you know 812 hours a day that's good thing though now that's a great thing to be moving but once you know that the long hours and just being of exertion with the mental exertion as well you know go and the emotional you're working with people you're trying to save lives here you know and so they take their jobs very seriously so mentally physically long hours that will sale that do you say that standing in one spot you leave your working as the technician and you often times especially in difficult case your holding a pose for a very very long time something being articulated something being cut out and you really are sacrificing a lot get you get aches pains etc. you probably absolutely accurate is this holding these Sina you want to move so understand back when I was a med student we had to do that yeah and you like a member universe aggressor redoing a gunshot wound like 2 AM in your hold his retractors and you start getting fatigue start shaken surgeon starts yelling at you like trying yeah three a little bit of sweat and I hope it's not going to fall into the sterile field you know yet is all kind of distress is that going on yet for sure but I think it's so over a long period of time I think that that that weighed a lot on me just with the stress that goes on with the environment and in that and then justly and not not being out and being active is much being indoors so it putting in those hours and you not try and hit on this in the past but what was your interpretation of maybe this is an institution of health that I'm in but make no mistake it's an institution and it absolutely needs an industry what did you think about the hospital industry where you're supposed to be delivering health and then maybe some of the execution of some of that as it is rolled out right and that's where you have met so morally I saw some things but didn't sit well with me being in that industry right. I saw that that said you have the patient the becomes accomplished someone that's there in the middle right and you have for me in a lot of cases you would have the insurance companies now and the doctors going back and forth and becomes more like an a number you know the patient becomes maybe a number of verses like eyelets really care what's going on here rather than like walking into be like okay who's is insurance what you know what the insurance here you know in and so that for me is like it was just a is one of the minor things but as one things got my attention you know that like it's it's not where the healthcare system is for me is like need to be more focused on you know the patient and patient health patient well-being rather than be no worrying about you know needed the money parts in the insurances and I know that out that all plays a very important role in it all for sure but I just cannot seem like there the patient was kinda being put to the wayside in this I now and so that was for me one of the indicators like I don't know if I'd want to stay in this enough for I make a career lie I know that the three or those that you referenced Rivero McKenna and have Blahnik they all were incredible patient advocate I will as I say so is the hard part I see nothing and struggle with it to it's like how can I deliver the service in can you know this a lot of times it's not even can I do this without insurance it's driving have a place to allow this you try to do a charity case here recently in almost got blocked when you're trying to give up your time and that kind of stuff gets in the way when you're like look I'm just trying to provide a service who needs it we get others who are able to basically start so yeah unfortunately it's super complex absolutely we have developed a system that is an organism that feeds on itself we have developed a system where will I crisscross or talk about all the time yeah we are trying to fix the end organ thing and trying to and then people have figured out how to make a profit on it right I remember listening to Peter Addie a talk one time or he's use a party thoracic surgeon I think is he really felt like he was at the bottom of the hospital and people were lobbing eggs yes try to catch the eggs like when we quit throwing the eggs out the window that and that's kinda what you're getting at where your mind I can see that you are very in tune to your feelings nature and everything and that's really cool that you took a step back and with wait a minute this is not for me write Dr. Bill to solve it so sure not to go to hospital ministration politics and arrive the eye that I was working I was editing blogs for a guy who's really in the sustainability name Rob Greenfield and when I was working with him I was like man how to weep back I would love to try to take on the medical industry and just the waste that they produce the thing I so I'd like to have the ambition again if I like how can this happen but then again you know it's such a he there so many things are going on with it but the act is something that I can't solve I took a step back and said well this I would I would love I know it's going on but I'm texted back and what's best for me and so that led to me I did take one last hurrah as a travel surgical tech when travel took some contracts the United States Tennessee, where my mind was on that oh it's not just wise Kelly not just a problem yeah yeah was there it was there a strong proverbial straw that, I was like you know what this is this the part that is nonnegotiable for me or was it just counted everything together kind of at EL it is all Elkanah came together and it was where I was in life any of these can I felt like a time to move on the I love the people I work with and and you know I was I enjoyed my time doing that but at same time as I was I was ready for more I want to be fulfilled I wanted to I need a challenge I need a challenge titled how old is your son of the sun so I have a daughter daughter she's eight right now so back didn't see you whenever I stopped all this you know she was 56 yeah yeah yeah really and so I imagine that you you left there for much more lucrative investment banking type thing yes so quite the opposite so what I did is I think a little money I did have and I purchased a school bus and herded into the camper and then spent the rest of money on Christmas gifts for the family that year in then yeah converted a school bus into a camper and went roaming around in the mountains of New Mexico and Libya Colorado and no plan really other than I wanted to get in the travel like I'm like now the time to do it I want to figure out a way to make a living no traveling so what do I do I get the school bus converted numb site I start inviting people on these adventures of the mountain second as I get a venture you know pay for gas give me a lecture and not show you great time have connections in New Mexico and Colorado and you know various other places in Texas so that was my first kind of entrepreneurial thing how people find social media yet is utilizing social media I started I became part of this group called superhero Academy I can find them superhero Kennedy.net or anywhere online and get a really good thing going on start learning about social entre nous or ship just how to utilize Facebook and Instagram and YouTube to make a living right to to purchase about their the brand yourself right so this is back in 2015 or so that I started the 2015 716 anyway so far I started that's how I started back the tyro knew like that's that's where I was posting this with my close community friends and family on Facebook and now this were my first few customers came from and went from there to a long bus or short bios have a short bus it was like when it was an old law wasn't it was a 1998 Thomas and it was more the shorter versions wasn't a long one but it was necessary like a short bus I was like one of those admitted weird big block at tween area as I get a big and blocky and now but it only had like 67,000 miles and was a diesel when I bought it from a kid that was moving down to Texas A&M and had it for his buddies to go fishing in and paid 4300 bucks for it and I was like this is a little nugget of gold right here that she sounds pretty awesome like it like your first year just ended up being like serial murderers are you by your Jason is a guy yeah my trash back to him he probably would've lightened up on my trip that we had a good time and that's what it was about that was about getting out and finding yourself in exploring and being out nature and also just the travel experience in the cognitive effects it does have on the mind and just in and just how healthy it I think it I think a lot of our health starts at are in our minor thought process in her brain so that's what I wanted to show people hate get out do what you love but also here's a healthy way to do it by getting outside and pushing yourself challenge yourself let's go skiing let's go snowboarding go kayaking you know let's go hiking up in the mountains so that's really cool that's actually the stuff you do it was a bit was like an adventure bus it was an adventure bus yeah and that's what it was absolutely Jerry problems with that that 98 diesel in the in the cold ever fired up yeah I mean to mean no serious problems there was a couple mornings are there were a couple mornings where if you select slow start but even use a fire right up and this thing was a beast it was it just ran and ran and ran and I think part of it is because it had low mileage and he was just kinda getting broken and you know like a decent run forever and ever and it is getting broken in but now it fired right up in the mountains that is the exact opposite of the job that you are doing is a surgical tech maps act opposite yeah that is a bit just real quick before we have 30 seconds to break but okay did you feel that the moment you began to engage with people on a personal level that suddenly now you're starting to feel an elevated mood versus always seen patients are asleep absolutely absolutely that was my favorite part of actually being in the surgery is like you know commuting with those patients before they were when it went under and in yes when I moved into and started talking people one on one that was where I really start to thrive wherever this Latin is half-hour ending in that joint to begin for the next hour but will be back in just a moment and that's not where his story stop seated at this is the only 24 hour take anywhere platforms dedicated to food and fun query spoony this our Townhall.com intelligence committee issuing subpoenas for former national security advisor Michael Flynn and former Trump Deputy campaign manager Rick Yates is part of the committee's ongoing investigation of counterintelligence issues raised by the molar report Committee Chairman Adam Schiff says the two have refused to cooperate 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Trump says there is no harm in lessening that's what he tells ABC's George Stephanopoulos who asked the president whether he would accept campaign dirt against a political rival, foreign sources somebody call from a country Norway we have information on your I think I want to hear Mr. Trump insisted simply listening to the information would not constitute outside interference in a US election Dr. higher on Wall Street this our Dow is up about 94 points NASDAQ ahead 51 S&P 500 index up 12 points more on the stories@townhall.com are you tired of high cable TV rates sign up for dish today and get a $500 bonus offer while supplies last loss lock in your price for two years guaranteed call American dish your dish authorized retailer now 800-570-6630 800-570-6630 that's 800-570-6630 offers required critical negation 20 from early termination supply call for details if you are trying to quit drinking or doing too many drugs listen to me you don't know me and will never meet I had a problem 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our number two episode 14 catching project check your ego at the door nothing is off the table where joining Dave I Cooper read digital and social entrepreneur and of course a maps advocate and a volunteer position to project we will get to that in just a moment but let's touch base again in case you've forgotten love my tummy.com/spoony get your discount on our Tron teal today in the big challenge for everyone everybody to commit buy a bottle for a friend or family member use that code Cusick is a winner there and don't forget if you really want to you really want to win subscribe and share the gut check project go to catch a project on YouTube to get a project to channel or search for catching project on iTunes subscribe then all you have to do is go to KB MD health.com or get check project.com connect with us let us know that you did it to be entered and draw at least five winners in July 5 words literally going to get the signature protection package which is trying to heal and KB MD CBD one month supply no cost to you enter as many times as you want the course will to see what happened to me of times you can subscribe so I but will will go that route if you're new to get your project we are hosted on the spoony network and there's an amazing array of shows that they are that dad Dr. Brown and I both have trying to take in as many episodes as we can everything from family meal was chef Mark Conway to know but it's too big to tryst with 20 that's with Alisa Shakespeare in a course the great Jeff Patrick Mosher's on this channel also so tune into this bony network if you ever want to learn a little bit about food it's not just gut check project on here talking about new innovations in health and new approaches it is also a lot about food and food science and improving the way to cheat would just try to make this is about make everybody better and were listening to Cooper talk about some really cool brave changes in his life he saw that his health was heading in the wrong direction pivoted and got that bus/camper started doing things so you start to discover nature and thinks a lot of things that I like to do sometimes with Eric all acts I'll ask him philosophy quotes if he can remember the philosopher who said it so here is the philosophical quote of the day reality is wrong dreams are for review rally is wrong dreams are for it that's that was what Tupac did Jesus talk was a philosopher man like EEA you know like say what you want about it but a lot of people love them but man is some content you just can't new to the game straight to the hip-hop repertoire not as nice Cooper welcome to the show the other episodes but yeah no you don't normally it said said little Wayne little Waylon today but I don't know I think is pushing the boundaries on so it's not it's not it's not silent geez and lasagna cheese lasagna is a boost as a whole website dedicated to little Wayne quotes posted in a wheelchair called a virgin mobile I have yours wrapped that truth that I just liked how what what points are you going to maps.org the new sailor cited writes music would you like to put all some of Everett is leading yeah you do it on the right some crazy. So hey we we left off last half-hour you are talking about that the bus you have any you have any experience in the busted may be didn't go exactly as planned yeah I had a couple know the one that sticks out the most though as we are in Taos New Mexico and it had been yet sounds what now love town elements my favorite so we were but we'd been there for about a week or so was with my brother and my friend Amy Shane we were descending at time of the mountain some other friends were over in Angelfire so we like minute but then down the mountains and it is time to go home and we came in on this like really sketchy like mountain trail it wears like I was I had been there several times and came in like the normal way but for whatever reason the GPS Lake was late go this direction and I like and save you yeah and I was like okay cool working to go this way in the back way in and so naturally like when we left like there was a hit there had been snow in and you know the temperatures drop to about to zero while we are there so we're heading out like go back that direction and see what happens and it was not a good choice we got up I was going uphill on these frozen Rosie on this is Charles all dirt you know this is just rocks and dirt and I might die and you and you a sketchy going up on Mike you know what I was gonna go with it and see what happens and no okay now we start sliding me know and I can't get it under control wind up I am trying to press the brakes at one point words, this incline gives airlines on this bus it and I don't even know honestly have no idea. It really cold yet you know we are just sliding and back back back back you know we cannot almost scan were going off of the mountain side a little bit was like a steep drop off but it would been something I could not of gotten out of so I tried to like steer it back in it just as I was sliding backwards or turn the wheel I turned the wheel and got it like just perpendicular with the road and try to pull out but even even turning in trying to get out of it is made the situation even more and I going into the bank of the road saying on the bus and everyone well after a lot of silence strays silence a lot of you like any nobody has a lot to home of the engine going and being out everyone just quiet like what like why did you take us this nightly understanding about adventure but I like this is not for us and he only is my brother is just back there shaking his head like I don't know how to get out of this is like I understand you got insured for the show exactly know this is go anyway so we go to the bank in the nose of the bus is stuck into the side of the road in the snow and all that so we had to get Dick to the city officials or the Rangers I think that the park ranger showed up in his big old snowplow monster truck looking thing comes out in the tie chain on and yank us out and get us going back the opposite direction back to the safe road is a trail used to make she made down yeah yeah they did they did because the rest of luckily I was like downhill so it is an easy cruise down but but that was a sketchy moment because like we are most went off the mountain backside and we crashed into the bank on the outside so so when you are following this snowcapped thing didn't have a bumper sticker that said if you can read this. It arises you know that I don't know if Manny was like I want to try to go at it that that's not I would not do I would only like Joe will like Mossad I totally admire you from doing that and I think that is what so cool you left this career you jumped in both feet and you start pushing your boundaries exactly inc

SHOW: 67SHOW OVERVIEW: Brian talks with Annette Clewett (@aclewett, Senior Architect @RedHat) and Travis Nielsen (@STravisNielsen, Senior Principal Software Engineer @RedHat) about software-defined storage, managing storage with Kubernetes, and how Rook is bringing the Operator model to storage systems like Ceph. SHOW NOTES:Try OpenShift 4 - http://try.openshift.comProject Rook - Storage Orchestration for KubernetesDeep Dive: Rook (video) - KubeCon 2018Ceph on OpenShift with Rook (video) - Commons Gathering 2019Rook Channel on SlackSHOW TOPICS:Topic 1 - Welcome both of you to the show. Before we get into discussing Ceph and Rook, can you tell us about your background around these projects? Topic 2 - One of the most frequent requests we get from listeners is to discuss how to integrate (and manage) storage into OpenShift/Kubernetes environments. Let’s talk about storage needs for OpenShift/Kubernetes infrastructure (masters, logging, monitoring, etc.) vs. storage for applications. Topic 3 - Help us understand the difference between a storage manager like Rook and a storage system like Ceph. Where does one start and the next one stop? Topic 4 - Rook now uses the Operator pattern for managing underlying storage systems. How does the Operator technology help make managing (and lifecycling) storage easier or more robust? Topic 5 - As you talk to users of Ceph and Rook, what are some of the best practices that you’re seeing them implement? FEEDBACK?Email: PodCTL at gmail dot comTwitter: @PodCTLWeb: http://podctl.com

Hey guysssss, Welcome to a new episode of JustUsGirlss Podcast. This week is all about the election of our dearest country. We discussed our various struggles of getting our PVCs, the poor treatment of youth corp members by INEC, the probability of Nigerians electing new candidate and other related problems. We hope you guys enjoy it, don’t forget to give this video a thumbs up or ratings depending on which app you are listening from. Also drop your comments, share, subscribe/follow us. Don’t forget to send us your questions either to our official twitter DM or our mail; justusgirlss@gmail.com Hosts; Topshay Twitter: mz_topshay Instagram: topshay__ Bimbo Twitter & Instagram: @b_moree_ Dayo Instagram: dayo.a

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Your heart can get out of rhythm. Dr. Gregory Marcus explores why the heart may beat too slowly or too fast, or in a disorganized or chaotic manner. Some of these different types of arrhythmias can be dangerous if not properly treated, while others may be annoying but are not life-threatening. Find out how to tell the difference. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 34162]

Dr Carolyn Lam:                Hello. We're here at the American Heart Association meeting in Chicago where circulation has 19 simultaneous publications this year. And that is a huge increase from six in the past to 19, all thanks to the man next to me.                                                 But first, let me introduce myself. I'm Dr Carolyn Lam. I'm associate editor from the National Heart Center and Duke National University of Singapore. I'm the voice you hear on 'Circulation On the Run'.                                                 I'm so pleased to be here in person today with Dr Dharam Kumbhani. He's associate editor from UT Southwestern and he also leads the simultaneous publications for this journal. So big applause for this amazing bonanza this year. Dr Dharam Kumbhani:   Thank you. Dr Carolyn Lam:                Next to him, we have Dr Sana Al-Khatib and she's from the Duke University. And finally, Dr Gabriel Steg from University of Paris. Wow! Okay, we've got 19 papers to chat about. No, I'm just kidding. We're going to talk and focus on the seven simultaneous publications that were late-breaking science.                                                 Why don't you start us off, Dharam. We will first start with the interventional trials, and there were three of them. I'd love you to chat about the first of them, but even before that, maybe, tell us what it's like to get a simultaneous publication. Because I think people underestimate the amount of work it takes to do that. Dr Dharam Kumbhani:   Thanks a lot, Carolyn. I think under Joe's leadership the whole space of simultaneous publications in late paying clinical science has really been a big endeavor for him and for the journal. We just have an amazing team that's able to work on this in very quick order. So, for the viewers, I think it's a very involved process, but it's a very gratifying process.                                                 We work very closely among the associate editors, the senior editors, and then the circ staff, and we have very rapid turnaround time. So we owe a lot of gratitude to our reviewers who frequently will turn these reviews in within 48 hours. Our goal has been that we respond back with a decision usually within five to seven days. So it's been very gratifying.                                                 Then it moves onto the next set of revisions, et cetera. But even among the papers that we are unable to accept for circulation, it's just a quick turnaround time for the authors so they haven't lost as much time and can potentially look elsewhere.                                                 It's been a really gratifying process. It's been a great, great team effort. I appreciate everything you said, but really I don't deserve all that credit. It's been a great team effort. Dr Carolyn Lam:                No, it's been rumored there's a lot of lost sleep on your end, so thank you, thank you Dharam for this. And maybe you could open with the ISAR-TEST 4, that's been [crosstalk 00:02:47]. Dr Dharam Kumbhani:   Yeah, well thank you. I think we had some really interesting interventional trials and Dr Steg will discuss a couple of them as well.                                                 ISAR-TEST 4 was a very interesting trial. It is one of the first 10 trials that gets to the 10-year mark, so this is just the 10-year follow-up results of that. It was about a 2500 patient trial. It was done in Germany, multiple centers. Really they were trying to assess the space that they were trying to ... Or the knowledge gap that they were trying to fill was the durability of the bioabsorbable polymer stents.                                                 Specifically, they were looking at a bioabsorbable polymer sirolimus-eluting stent, the Yukon stent, and then they compared that with durable polymer stents including Xience or the everolimus-eluting stent and then Cypher, which is no longer available in the U.S., but that's a permanent polymer sirolimus-eluting stent.                                                 The primary results were published and presented a long time ago. There was really MACE events at one year and it showed non-inferiority for this bioabsorbable polymer stent back then. So, then they had, incredibly, 83% of the cohort that they were able to follow-up out of 10 years. And what they showed is that ... I don't want to necessarily get into the numbers and the details as much, but what they showed is that this bioabsorbable polymer sirolimus-eluting stent tended to have similar outcomes to Xience, which we accept as state of the art current generation stent, permanent polymer. And it did better than the Cypher stent, both in terms of MACE events and stent thrombosis.                                                 So suggesting that, the big advance in the field for this is ... This is a long-term follow-up of the stent. It suggests that outcomes may be similar in this patient population. Although only 12% were really enrolled with an MI in this patient population. Most of them were stable or less sick ACS patients. And they show fairly good outcomes out of 10 years, comparable to Xience and better than Cypher.                                                 I think it was interesting. Gabriel, what is your take [crosstalk 00:04:57]. Dr Gabriel Steg:                I think it's important. There's been a tremendous interest in international community on trying to tease out which are the best types of stents and beyond brands, try to understand the type of stent, the coating, the drug that you put on it, whether the polymer is durable or not durable. I think these types of fairly well done, large randomized trials with long term flow are critical.                                                 A lot of the focus in the interventional community originally was on lumen size, late loss, angiographic parameters short term. And now the field has matured, and we've moved to clinical outcomes, patient-oriented outcomes, long term follow-up. And it's important because we've learned from long term trials such as PROTECT that the result at one year may not predict what happens at five years, and sometimes you have surprises.                                                 So, it's really important. We owe it to our patients because these are irretrievable devices. Once you've implanted them, they are there. We talked about Cypher being out of the market, but there are more than a million patients who walk every day on this plant with a Cypher in their coronary artery, so we better know what the long-term follow-up is. Dr Dharam Kumbhani:   Yeah, that's a great point. Dr Carolyn Lam:                Wow. And then thanks also for the discussion that allows me, as a noninterventionist, to realize ... It's hard to keep track of what's happening with all the different types of stents and polymers and so on. But could you then summarize for the field, does that mean that these biodegradable ones are now ... Do I sound ignorant when I say that? That they are now really in the game. Is that what it does? Dr Dharam Kumbhani:   This whole bioabsorbable field, there are nuances. So this really is testing a bioabsorbable polymer where - Dr Carolyn Lam:                Oh! Dr Dharam Kumbhani:   So, with every stent you have a stent, you have the polymer, and then you have the drug. Dr Carolyn Lam:                Thank you. Dr Dharam Kumbhani:   And so, the polymer and the drug go away, and then you're left behind with a bare metal stent. And that's this Yukon stent. Dr Carolyn Lam:                Got it. Dr Dharam Kumbhani:   The one that has been in the press a lot more is the bioabsorbable scaffold where the stent and the polymer and the drug, everything in theory should be gone at a certain period of time. So this is ... It's an important distinction though. Because I know that it's very confusion when you just say bioabsorbable and it's unclear if you're talking about the polymer or you're talking about the stent, itself. But this really was a bioabsorbable polymer issue, so you're left behind with a bare metal stent at the end of it. Dr Carolyn Lam:                Got it, crystal clear, and thank you. That's cool. That's super. Dr Sana Al-Khatib:            I agree, for an electrophysiologist too. Dr Carolyn Lam:                But now, let's go into the AMI field. There were two trials that really spoke to acute management patients coming in with an AMI and with cardiogenic shock, for example. Gabriel, could you tell us a little bit about the IABP-SHOCK II trial, as well as the really talked about a door-to-unload IMPELLA Trial. Dr Gabriel Steg:                The IABP II trial is a randomized trial looking at the benefit, or lack thereof, of intraaortic balloon pump in patients with cardiogenic shock and acute MI. It's been standard practice since the '60s to offer IABP pumping to patients with cardiogenic shocks and AMI.                                                 So, literally more than a million patients have been implanted with IABP, but the reality is when we look at the randomized trial evidence of benefit there was none. They were very small trials, inconclusive, underpowered. Professor Thiele from Germany and his colleagues deserve enormous credit for having had the courage to really do what needed to be done. A proper randomized controlled trial, of course open label.                                                 And what they found in IABP II, which they already reported a few years ago, was that there was no acute benefit of IABP on survival short term, or for that matter on many of the secondary clinical outcomes looked at in this trial. They subsequently reported one year mortality.                                                 What they did here is they gathered follow-up on almost all of the cohort at more than six years. And they found that the long term survival is identical for patients who received an IABP and those who did not. So I think this nails the issue. But there's another thing we learn. The mortality at six years is staggering, it's close to 60%. And although a large fraction of the patients die in the first 30 days, you still have an additional 10% of patients who die between the first year and six years.                                                 So there still remains a very sick patient population for whom we need to investigate new strategies. I don't think it's going to be necessarily mechanical. We have to think of all of the strategies we do to prevent and mitigate cardiogenic shock to build up. And that's gets us to the second trial that I'll talk to you about in a minute. Dr Sana Al-Khatib:            I have a quick question about this. Did they provide any information about modes of death in these patients? Dr Gabriel Steg:                Yes. They did capture information about that. Off the top of my head, I'm unable to provide information, but yes they did capture that. The German system allowed them to retrieve information about causes of death and it's a closed system. It's a national trial, so they were able to get enormous follow-up. Dr Sana Al-Khatib:            Because this information can help us inform what interventions are needed next. Dr Gabriel Steg:                Yes. That's really important. Dr Dharam Kumbhani:   To your point about ... You use a very interesting word, the last nail. That's actually how Dr Hochman addressed her editorial. She wrote a really nice editorial- Dr Gabriel Steg:                The leading expert in the field. Dr Dharam Kumbhani:   And so, I'm interested in your thoughts. The use of balloon pumps for shock, there's a discrepancy between the American guidelines and the European guidelines. Last year the European guidelines were updated. It is really such a practice changing guideline in that it now lists routine use of balloon pumps in cardiogenic shock- Dr Gabriel Steg:                Class III. Dr Dharam Kumbhani:   -as a class III indication. Going through training, that was all you had when someone came in with shock, you would throw in a balloon pump. So that's really quite a practice changing event. Dr Gabriel Steg:                Yeah. These investigators are embarking on new studies with ECMO and I think it's going to be fascinating to see whether ECMO, which also gets increasingly used worldwide, whether there is evidence to acutely support or not whether this is useful. I think they are doing the proper thing. They are doing the right thing, randomized trials. And we could commend them because these are really difficult trials. Dr Carolyn Lam:                Absolutely. Dr Gabriel Steg:                In the acute MI setting, shock patients, ECMO, IABP, that's really difficult. They are brave investigators, they are good investigators, and I think they provided the community with a clear answer. Dr Carolyn Lam:                And exactly the kind of papers that we like publishing at circulation, isn't it? Now what about the door-to-unload? Dr Gabriel Steg:                That is actually a good segue with door-to-unload because if we can't properly treat shock once it's there, can we do something to prevent shock? Can we do something to preserve myocardium? One of the experimental findings that is very clear is that if you unload experimental myocardial infarction, if you unload the left ventricle you reduce infarct size. Dr Gabriel Steg:                So, investigators have been trying to translate this experimental finding into the clinical arena using the Impella device. There's enormous interest, particularly in North America for Impella use in acute MI patients with larger infarcts with the idea that if you can unload the left ventricle, you might be able to mitigate the extent of the myocardial infarction, and therefore avoid cardiogenic shock and probably improve prognosis.                                                 Although this is a very attractive theoretical concept, it still deserves to be tested. And so, if you want to test it you have to unload the ventricle as soon as possible, ideally before reperfusion, which means that you're going to have to delay reperfusion for the time of implanting the device and unloading the ventricle. And so what the investigators did in this trial is to study whether delaying proposedly by 30 minutes reperfusion, to unload the ventricle for 30 minutes prior to reperfusion, was feasible and reasonably safe.                                                 It's a small trial. It's really a pilot trial. By no means does it test the proof of concept of the device or the theoretical issue, but it shows that it's feasible. There doesn't seem to be a massive increase in total time to reperfusion because just by change the group that was not delayed had a longer time to PCI, so eventually things are sort of evening out.                                                 They looked at MRI size of infarcts at follow-up. There was no obvious difference, but of course it could still be tied to errors. We're not totally sure about this, but it certainly paves the way for doing a proper proof of concept randomized trial, testing unloading versus no unloading with a true control group. And I think that's what investigators are looking forward, but I understand there's immense interest for this concept in international community, particularly in the United States and I'm quite curious to see what this future trial will look like and what the results will be. Dr Carolyn Lam:                Yeah, indeed. Gabriel, I noticed you were very careful to frame it, to say what the trial was trying to address and what it wasn't. And there's been quite a bit of buzz after that.                                                 Do you agree with everything Gabriel has said and what have you heard? Dr Dharam Kumbhani:   I think he was incredibly eloquent in outlining the premise of the trial and what it really showed. I think the one thing that ... And this was brought up in the very nice editorial by Dr Patel from Duke as well, is it would've been really nice to have a control arm which didn't have any unloading. Because these are not patients with shock, that just directly had primary PCI. And then comparing infarct size.                                                 So, I think that was one of the pieces of information that would've been helpful to then put this in perspective. When you have an infarct size of 8% or 10%, how does that compare in the same patient population in their testing? You're absolutely right about the need to do difficult trials like this, where a lot of times it's just assumed to be true and is embraced in clinical practice.                                                 As I gave the example about the balloon pump earlier, where as a Fellow you saw someone in shock and your reflex was to put in a balloon pump. And so, I think testing these very difficult patient scenarios, as well as just in terms of trial execution, it's amazing to have two trials on that. Dr Gabriel Steg:                If I may come back to this? Dr Carolyn Lam:                Yes. Dr Gabriel Steg:                It's funny because we've been using the IABP for years, thinking this is what we should do in shock. Now our German colleagues have proven that IABP doesn't work. So a lot of investigators have reverted, saying "Well, we should use Impella." But where is the evidence showing that Impella is beneficial? Dr Dharam Kumbhani:   That's right. Dr Carolyn Lam:                That's right. Dr Gabriel Steg:                We have none, so I think that's a trial that deserves to be done. Dr Dharam Kumbhani:   And ECMO. Yeah, exactly. Dr Carolyn Lam:                Yeah, ECMO. Exactly. And, you know, going back to door-to-unload, it's important to prove safety in order to go to the next step, which is exactly how you frame- Dr Gabriel Steg:                I think it shouldn't be over interpreted. Dr Carolyn Lam:                That's how it should be, exactly, received by the community. So that's great. Now let's switch gears a bit.                                                 Sana, in EP world, the EP guided noninvasive radio ablation of VT. Fascinating stuff. What are your thoughts? Dr Sana Al-Khatib:            I absolutely agree, definitely. This was a phase two study that the authors did. They enrolled 19 patients, so it was a small study, but it was really helpful. Remember, there's a major clinical need there. These are patients who have an ICD, who have recurring ventricular tachycardia, that have been treated with at least one antiarrhythmic medication, at least one catheter ablation procedure, and then what do you do with those patients? This is actually a clinical scenario that comes up frequently and we absolutely need to be looking for more therapies for those patients.                                                 So that's what that study was about, trying to explore new ways to treat these patients. To be able to do it noninvasively, I think is fascinating. That's what ... They enrolled these patients. Patients had to have failed these treatments, antiarrhythmic medications, prior catheter ablation, and they underwent noninvasive imaging to really localize the source of the ventricular tachycardia, where it's coming from, and then they subjected them to stereotactic body radiotherapy to ablate those sources of ventricular tachycardia.                                                 And, of course, the results were fascinating because they showed on the effectiveness side that this seemed to be very effective because if you look at the reduction in the burden of ventricular tachycardia, and a couple of their patients actually had significant PVCs and PVC induced cardiomyopathy, there was a significant reduction in the rates of these arrhythmias in these patients with this intervention, which was great to see.                                                 In fact, to be specific, about 94% of these patients, so 18 out of the 19, had significant benefit. And in about 89% of the patients there was more than 75% reduction in the arrhythmia. So these are actually really interesting findings, especially in a patient population where we really don't have other options. Now of course you're going to ask me about the safety. What are the safety concerns?                                                 Of course, this was a primary endpoint for the authors. They did look at safety up to 90 days and they found that there were two significant adverse events that occurred in those 90 days. One was heart failure and one was pericarditis. The concern, of course, with radiation is what else can we expect especially if you follow the patients longer? So certainly we need more data. The authors acknowledged that beautifully and I think their intent is to launch a multi-center randomized clinical trial. I don't know if it will be randomized, but at least a multi-center clinical trial to see if they can replicate those findings. So that was very interesting to see. Dr Carolyn Lam:                Yeah it was. Thanks, that was really exciting.                                                 So, some exciting trials in my world of cardiometabolic disease too, and I want to highlight two. The CARMELINA trial and the CAMELLIA-TIMI 61.                                                 First the CARMELINA trial. This was a secondary analysis of CARMELINA and this was ... CARMELINA, if I can remind everyone, is a cardiovascular outcomes trial, randomizing about 7000 patients with type 2 diabetes and atherosclerotic cardiovascular disease, and/or chronic kidney disease. Randomizing them to the DPP-4 inhibitor linagliptin 5 mg a day versus placebo, following up for a median of about two years.                                                 We know that type 2 diabetic patients are at risk of heart failure and there's always been a bit of a question mark when it comes to DPP-4 inhibitors and their risk for heart failure. And so this secondary analysis looks specifically at the hospitalization for heart failure and related events in CARMELINA. The important thing is that all these were prospectively centrally adjudicated events, and this was a pre-specified post hoc analysis.                                                 And the summary of it all is that linagliptin was not associated with an increased risk of hospitalization for heart failure or the composite of cardiovascular death in hospitalization or the related outcomes. Importantly, the authors did also sensitivity analyses and interaction analyses to show that the results were consistent whether or not patients had a history of heart failure, which was in 27% of patients, regardless of the baseline ejection fraction that was measured within a year of starting the drug, and also regardless of renal function. So EGFR or urinary albumin to creatinine ratio.                                                 This is really important because this trial adds to the growing perhaps understanding of DPP-4 inhibitor heart failure risk. The whole question mark actually came with SAVOR TIMI and that was saxagliptin. But since then there's been three other trials that have showed no heart failure risk. EXAMINE, TECOS, and now CARMELINA. So, an important addition and I think it should reassure us.                                                 And then from diabetes and heart failure risk, which is always very hot, but now obesity. The CAMELLIA-TIMI 61 trial looked at renal outcomes in this trial. Now what was this trial? It was actually testing lorcaserin, and that is a selective serotonin 2C receptor agonist, in about 12,000 obese or overweight patients.                                                 Basically, the primary results showed that it did not increase any ... It met it's CV safety outcomes with weight loss and so on. But this time they looked at renal outcomes. Because obesity has been known to be associated with hyperfiltration of the kidneys, you get albuminuria and it's apparently worsening of kidney disease. So what we need to know is pharmacological weight loss going to be associated with improved renal outcomes?                                                 And basically, that is what CAMELLIA-TIMIA 61 showed. Their renal outcomes were new or persistent albuminuria and then the standard doubling of EGFR or end-stage renal failure, renal transplant or renal death. And that was improved by lorcaserin. Along with that, there was the anticipated reduction in weight, HbA1c, and BP. It does look like, from these late breaking results that we have another tool in our toolbox. Dr Sana Al-Khatib:            And for the clinicians out there, which patients should they be thinking to use this medication in? What kind of obesity are we talking about? At what point do you introduce that? Dr Carolyn Lam:                This is common garden, just defined by BMI that was above 27. And I don't think they're saying to use it in patients with renal dysfunction, but to sort of say to look and see whether weight loss also associates with renal function improvement, and it does. It's reassuring. Dr Sana Al-Khatib:            Yeah, okay. Dr Carolyn Lam:                And then ... Okay, let's round up with that last trial. A very interesting one because it's pragmatic mobile health and wellness. Tell us. Dr Dharam Kumbhani:   It's really a monumental effort. This is ... I'll be brief, but it's really a phenomenal trial from an epi standpoint and implementation standpoint. This is from India. It was coordinated by the Center for Chronic Disease Control and the Public Health Foundation of India where, as everyone knows, India is now the diabetes capital of the world and chronic diseases have very quickly overtaken other infectious causes as the number one cause of mortality and morbidity.                                                 This was a big undertaking, really collaboration from three continents, but it was a community based plus a randomized trial. They had 40 community health centers and what they were trying to see is primarily for hypertension and diabetes. That if you implemented a structure and typically using this mWELLCARE tool, which is basically an electronic medical records storage facility and then it also has inbuilt clinical decision support.                                                 And really for hypertension and diabetes management, but also, they had tobacco and alcohol screening, abuse screening, and also for depression. So what they really wanted to do ... A very ingenious endeavor and they try to see if doing this systematically on a clustered randomized fashion if that would actually influence patient outcome. They had a little over 3000 patients and they followed them for 12 months.                                                 Unfortunately, the trial, itself, as far as the primary endpoint, which was change in systolic blood pressure and hemoglobin A1c, they had pretty significant reductions in both arms, about 12 to 13 millimeters, which is amazing from a population health standpoint, in both arms not statistically significant, and in hemoglobin A1c also by 0.5% in both arms.                                                 Just suggesting that having this more frequent interactions with the medical health system, itself, was driving a lot of this benefit. So although the trial, itself, was negative for the primary endpoint, I think it's a huge step forward for the management of chronic disease epidemiology and burden in developing countries. Dr Gabriel Steg:                Neutral. Dr Carolyn Lam:                Ah, true. Dr Dharam Kumbhani:   Fair point. Dr Carolyn Lam:                We've discussed this whole array of seven trials and they are difficult trials. I mean, talk about another difficult type of trial to do, cluster randomized pragmatic trial. It's amazing the breadth of simultaneous publications we've had this year. Thanks again to everyone for introducing this and thank you for joining us today.  

Jim Murrell is commonly known on YouTube as "The Transplant Helper" due to his YouTube channel full of episodes helping the transplant community. Jim was born with a congenital heart defect known as transposition of the great arteries. The Mustard Procedure helped Jim to live until adulthood and then he began having problems. Listen to find out what kind of rhythm issues Jim had and what was required to help him survive. Tune in to hear about Jim's journey and what caused him to begin his YouTube channel.Support the show (https://www.patreon.com/HearttoHeart)

Transcatheter aortic valves delivered better hemodynamic valve performance and less structural valve deterioration than surgical valves over 6 years. Transcatheter aortic valves outlast surgical valves in the NOTION study presented at EuroPCR. From Heart Rhythm 2018, a registry study suggests myocarditis is the culprit in many cases of frequent premature ventricular contractions, and one set of Botox shots into intracardiac fat pads cut atrial fibrillation for up to 3 years. Also this week, many patients with NAFLD and abnormal alanine aminotransferase should be taking a statin but aren’t, and why statins reduce the risk of lethal prostate cancer. Listen to Cardiocast weekly for all the latest cardiology news.

Transcript is below pic.  Season 1 Episode 8 Ehlers Danlos Syndrome  In this episode we interview one of our PodcastDX co-hosts, Jean Marie.  As you remember, she also discussed one of her EDS co-morbidity disorders (POTS) in a recent episode.  Today we ask Jean to share a little more detail of her Ehlers Danlos Syndrome and how that ties in to her complex medical diagnosis.  EDS is more than just being "really flexible" as you will soon learn.   TRANSCRIPT Ron: [00:00:30] Hello and welcome to another episode of podcast DMX. The show that brings you interviews with people just like you whose lives were forever changed by a medical diagnosis. [00:00:40][10.4] Lita: [00:00:41] I'm Lita. [00:00:42][0.2] Ron: [00:00:43] I'm Ron. [00:00:43][0.2] Jean: [00:00:44] And I'm the guinea pig. [00:00:45][1.0] Lita: [00:00:47] Collectively we are the hosts of podcast D X this podcast is not intended to be a substitute for a professional medical advice diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or a treatment. And before undertaking a new health care regimen and never just regard professional medical advice or delay in seeking it because of something you have heard on this podcast. [00:01:16][29.6] Jean: [00:01:18] Now on future episodes we have many interesting people to speak with about a wide variety of different medical conditions and diagnoses but in this episode we will be discussing a rare set of disorders that fall under the category of Ehlers Danlos syndrome which we will abbreviate from this point forward as E D S. [00:01:39][20.9] Ron: [00:01:41] E D S or a group of connective tissue disorders that can be inherited and are varied both in how they affect the body and in their genetic causes. They are generally characterized by joint hyper mobility that is joints that stretched further than normal, skin hyperextensibility. Again, skin that can be stretched further than normal, and tissue fragility. There are 13 subtypes, each one being diagnosed through genetic testing. The hyper mobile type does not have a genetic marker identified just yet. This type is diagnosed by a physician using something called the Beighton Scale, which includes a variety of tests to give reference to the amount of hyper mobility involved in the patient. The connective tissue of a person with EDS is not structured the way it should be. Some or all of the tissue in the EDS affected body can be pulled beyond normal limits which causes damage connective tissue can be found almost anywhere. It can be found in the skin the muscles tendons in the ligament the blood vessels the organs in the gums the eyes and so on you get the picture. [00:02:58][77.6] Lita: [00:02:59] That's right. Run. I bet you got that right off the EDS Society website. [00:03:03][4.1] Ron: [00:03:04] Was it that obvious? I wanted to make sure that we were giving the most accurate definition to the listeners out there. The link for EDS Web site along with more detailed information regarding EDS can be found on our Web site PodcastD X dot com. [00:03:21][16.9] Lita: [00:03:22] Well now that we know the definition of EDS, I guess it's time to point out the actual symptoms that a person with us experiences. The first is typically joint hyper mobility loose or unstable joints which are prone to frequent dislocations and or a subluxations, joint pain, hyper extensible joints., (they move beyond the joints normal range) and early onset of osteoarthritis. [00:03:52][30.1] Ron: [00:03:55] Lita, what's the difference between a dislocation and subluxation. [00:03:57][2.2] Lita: [00:03:59] Well a dislocation is defined as the separation of a human body's two bones from a joint or area where the two bones come together. In time, if treated incorrectly. It can lead to ligament or nerve damage, which will hinder the patient's body movements. A partial dislocation is referred to at times as a subluxation. This is the result of an incomplete separation of the bones that come together at the joints. [00:04:28][29.1] Ron: [00:04:30] Wow. Either way they both some pretty painful. [00:04:32][1.9] Lita: [00:04:32] They sure do. Pain is a huge problem with EDS. It can also turn into a chronic early onset debilitating musc, musculoskeletal pain similar to fibromyalgia. Another common issue with EDS is a skin related problems. It's very common to have fragile skin that tears or bruises easily, bruising may be severe. Severe scarring, slow and poor wound healing, even following a surgery, scars can reopen after you think they were healed. Other problems can occur within the body due to lack of collagen and or ligaments support. Things like frequent hernias, digestive problems, mitral valve prolapse, scoliosis, uterine fragility, and gum disease. [00:05:24][51.8] Ron: [00:05:26] That certainly is an incredible array of symptoms. And this disorder is not curable but it is managed with medication physical therapy and rest. So now that we have laid some of the background for our listeners at home it is time to introduce today's guest who unfortunately deals with EDS on a daily basis. Our own co-host here podcastDx, Jean Marie. Could you please explain a little bit about your journey with EDS?. [00:06:00][33.8] Jean: [00:06:01] Sure. I didn't know what it was but I've been, but I knew that I had some issues with my joints stability and such for some time. When I was little, I was always very "bendy" and my hip will go out of joint just walking and my shoulders would come out of joint several times, and I've had some other issues but I've had some severe problems with it as well, but most of my issues were later in life. [00:06:30][29.2] Ron: [00:06:32] So the first symptoms that when you were much younger you said about your hip. [00:06:37][5.3] Jean: [00:06:38] Well I would say that although I recognize that there was something going on I didn't understand what. How complex and difficult the situation was and that I had EDS until much later in life, in my 30s. [00:06:52][14.3] Lita: [00:06:53] Is it common for people with EDS to get a diagnosis of fibromyalgia. [00:06:57][3.3] Jean: [00:06:58] Sure. I mean you have joint issues and joint pain is often common in eds. So you may be diagnosed with fibromyalgia but it's actually a connective tissue issue when it comes to eds and you could also have an issue with your vascular system which is a subset of eds. [00:07:18][19.5] Lita: [00:07:18] Okay. And how do gastrointestinal problems. Irritable bowel or Gerd. How do those play a part with EDS? [00:07:27][8.2] Jean: [00:07:27] Well since your gastrointestinal system is comprised of connective tissue it can be affected by eds. So in your nerves are also surrounded by connective tissue. So since your gastrointestinal system works on a umm [00:07:43][16.0] Lita: [00:07:49] The pulsing of the muscles that move the product through the gastro system right? [00:07:55][6.0] Jean: [00:07:55] Right. That's all influenced by your nerves. And it's not something that you can control. It's an autonomic function and it's controlled by your nerve. So if your nerves are affected by your eds then your gastrointestinal symptoms are affected by that as well. And did I mention brain fog. I think brain fog is a part of eds. [00:08:13][17.7] Lita: [00:08:13] yes I know I know. [00:08:14][1.0] Ron: [00:08:16] Well I know your symptoms have changed over the years. This is based on surgery's medication changes etc. etc.. How would you say that eds affects your lifestyle right now. [00:08:27][11.6] Jean: [00:08:28] Well I have to make different modifications and accommodations for eds. Yes I have to take into account that my. For example I my hip might come out of joint and I do utilize different. Things to try to reduce the number of incidents I have. [00:08:45][16.7] Lita: [00:08:46] OK. Well since this is you know this is EDs Awareness Month as you know. Are you up for that EDs challenge that they've been talking about. [00:08:54][8.1] Jean: [00:08:55] Nope [00:08:55][0.0] Lita: [00:08:58] (laughter) Good. Let's do a lightning round. I'll ask the questions and you'll have 15 seconds to answer before I go on to the next one. [00:09:04][6.4] Jean: [00:09:05] Great. [00:09:05][0.0] Lita: [00:09:05] . Ron you'll keep time. You're ready. [00:09:07][1.9] Ron: [00:09:08] I Certainly am. whenever You're ready. [00:09:09][0.9] Lita: [00:09:10] Jean said she's not ready. [00:09:11][1.5] Ron: [00:09:12] Well you're ready Ready or not. [00:09:13][0.9] Lita: [00:09:13] That's right. OK. Question 1 What type do you have. [00:09:17][3.5] Jean: [00:09:17] Hyper mobile. [00:09:18][0.3] Lita: [00:09:19] And when were you diagnosed. [00:09:19][0.8] Jean: [00:09:20] Several years ago before my cranial cervical fusion in New York. [00:09:23][3.1] Lita: [00:09:25] OK. Do you have any comorbilities. [00:09:26][1.4] Jean: [00:09:28] Yes I have pots which we discussed on a prior episode. I get migraines. I have several hernias. I have an issue with my gastro parasen, paracentesis there say that three times fast. I have thyroid disorders tinitis in my ears cranial cervical settling and cranial cervical instability which has been repaired with a number of different titanium accessories, syncope is lipo edema, latex sensitivity I get PVCs with my heart. Now I have celiac disease and I have difficulty swallowing just to name a couple of related issues. [00:10:05][37.7] Lita: [00:10:06] Hey Ron I think we have a client here that we can use for a lot of future podcasts [00:10:10][4.1] Jean: [00:10:11] Oh no no no no. There are many other people that want to get on the show. [00:10:14][3.3] Lita: [00:10:14] OK. All right. Question number four do you have any mobility aids that you use. [00:10:20][6.0] Jean: [00:10:21] I do. There are some are unusual but it's difficult. For example for me to squeeze a bottle. So when it comes to toiletry products and things of that nature I use a pump. [00:10:31][9.7] Lita: [00:10:31] OK. [00:10:31][0.0] Jean: [00:10:32] Because that makes it my life much easier and I join up to worry about my fingers going out of joint. I also make sure that I you know I have trecking polls to assist when I'm walking and if need be I also use a wheelchair when I know when that comes. [00:10:46][14.6] Lita: [00:10:48] To much walk. [00:10:48][0.5] Jean: [00:10:49] And yet when walking becomes too much I wear very comfortable shoes that offer a great deal of support. And I just try to take it easy and rest. [00:10:58][9.5] Lita: [00:10:59] OK. What do you use for pain management. [00:11:01][2.1] Jean: [00:11:02] Anything I can. I've taken everything from fentanyl to oxycodone and I have recently submitted my application for medical marijuana for the state of Illinois. So I'm looking forward, looking forward to trying that as well. And then I also use things like distraction music. I'll read books listen you know watch movies spend time with my family spend time in the garden and I try to you know alleviate my pain through other techniques as well. [00:11:33][30.7] Lita: [00:11:34] And pet therapy. [00:11:34][0.8] Jean: [00:11:35] And pet therapy yes. [00:11:36][0.6] Lita: [00:11:36] Can't forget Buddy and Gi.Gi.. [00:11:37][1.0] Jean: [00:11:38] Nope. [00:11:38][0.0] Lita: [00:11:39] Have you had any surgeries do to eds. [00:11:41][1.8] Jean: [00:11:41] Yes yes. My , when walking my ankle. the tendons and ligaments tore off my ankle. So they had to be repaired. And I have not yet had my other ankle repaired but there is a similar situation there. And I also had a cranial cervical stabilization procedure to try to keep my neck stretched to its full full height. And it added a nice little inch to my height. [00:12:08][27.0] Lita: [00:12:09] OK. Have you had any hospital stays. [00:12:11][1.9] Jean: [00:12:11] Yep. One or two variety of reasons. [00:12:14][2.5] Lita: [00:12:14] What types of specialists do you have. [00:12:16][1.5] Jean: [00:12:17] I have a specialist for everything from my vision. So I have a neuro ophthalmologist straight down to my toes and I have an orthopedist that works specifically on ankle repairs. [00:12:31][14.1] Lita: [00:12:32] OK. What is your funniest EDS story. [00:12:34][2.8] Jean: [00:12:35] Before I knew I had eds I would entertain people by moving my hair around and it looks like it's a wig because I can move it so much because of the flexibility. So it's a little bit unusual. [00:12:46][10.4] Lita: [00:12:47] Mm hmm. Excuse me. What was your worst doctors experience. [00:12:51][4.1] Jean: [00:12:52] I had an orthopaedic surgeon told me that my shoulder blade was fine because I hadn't fractured my clavicle which I didn't realize in order to hurt your shoulder blade. You have to fracture clavicle but I don't think that's the case. And indeed I needed extensive repair to my shoulder blade and had to have two major procedures for that. [00:13:11][19.0] Lita: [00:13:11] Okay. And what was your best doctors experience. [00:13:14][2.6] Jean: [00:13:14] I have amazing GP's that juggle all of the specialists that I have and they're able to consolidate everything and handle all of my new and unusual conditions. [00:13:29][14.0] Lita: [00:13:30] OK so you say the gps would be the best. [00:13:32][1.9] Lita: [00:13:33] Yes. OK. Do you consider your she's doing pretty good on time. [00:13:36][2.8] Ron: [00:13:36] She is. [00:13:36][0.3] Lita: [00:13:37] Do you consider yourself. [00:13:37][0.6] Jean: [00:13:38] Since I forgot where I put my my notes. This must be an off the cuff. Yeah. Yeah. [00:13:43][5.0] Lita: [00:13:43] Do you see. Do you consider yourself disabled. [00:13:45][1.6] Jean: [00:13:46] No. No. I may be differently abled. [00:13:48][2.3] Lita: [00:13:49] Have you experienced ableism. [00:13:50][1.5] Jean: [00:13:52] is that like Cain and Abel ism or. I don't know what it was. [00:13:55][3.2] Lita: [00:13:55] This was one of the questions on the I'm assuming a challenge. [00:13:58][2.6] Jean: [00:14:00] I don't know. [00:14:01][1.1] Jean: [00:14:01] I do know that when I'm sitting in using my wheelchair sometimes people don't look at me or talk to me they'll talk to whoever is assisting me at the time and I find that disconcerting and that I've had issues in certain situations where I can't speak to someone and it does because it's the desk is so high and when I'm going on a tour of a museum it's difficult because you know you're trying to see everything. It's just there's challenges in that regard but nothing too horrific. [00:14:31][29.4] Lita: [00:14:33] What is something that you wish everyone understood about eds. [00:14:36][3.6] Jean: [00:14:37] oh... About Eds. [00:14:38][0.6] Lita: [00:14:38] Yes. [00:14:38][0.0] Jean: [00:14:38] Yeah. You say because you really do have to narrow it down that you can't necessarily see what's wrong. So if I am parking in utilizing a handicapped parking place it might be because my hip has popped off the day. And you might not be able to see that because you know you can't see that and you can't see other issues. But I do need assistance from now, you know every now and again and. Yeah. So just you can't always see what's going on with somebody. [00:15:04][26.1] Lita: [00:15:05] So it's an invisible illness. [00:15:06][1.0] Jean: [00:15:06] It can be. It can also be a very visible illness because I do have quite a few scars. And it takes me a very long time to heal. So in that regard you can see it. But yeah most of the time you cant tell what's going on. [00:15:18][11.3] Ron: [00:15:18] From the naked eye if people don't get you in a wheelchair they think you're fine. [00:15:21][2.9] Jean: [00:15:21] Yes. Yes and I could very well be passing out or having a syncapal episode at any moment and that's very frightening. [00:15:29][8.0] Lita: [00:15:31] True true it scares the heck out of me I know. [00:15:33][2.5] Lita: [00:15:34] Sorry Mom. Yeah. Yeah. If you could rid yourself of one EDs symptom which would it be. [00:15:40][5.9] Jean: [00:15:42] I guess the gastrointestinal complications I've been told that I should really have my colon removed and that's not something I'm jumping for joy about so certainly I'd want that corrected. And I guess any of the. [00:15:55][13.3] Lita: [00:15:56] No one one, you see how, she's that, now she's losing the trick. [00:15:59][3.5] Jean: [00:16:00] Well yeah. All right all right. Any. But yeah. OK. [00:16:02][2.6] Lita: [00:16:03] Just one. Well that wraps up today's session. If you have any questions or comments related to today's show you can contact us at podcast D X at yahoo dot com through our Web site podcast D X dot com at our Facebook page at Instagram or Twitter. [00:16:22][18.8] Ron: [00:16:23] And if you have a moment to spare please give us a five star review on I tunes podcast app. [00:16:29][5.6] Jean: [00:16:30] And thank you to all of our followers on Instagram. We really appreciate the feedback. And on Facebook I love all the feedback there as well. And the Twitter followers too, have to give you guys a shout out into all of our other podcasters out there who have given us praise and assistance and encouragement. We appreciate you guys. [00:16:49][19.5] Lita: [00:16:49] Yes we are. We're. moving... (forward) [00:16:49][0.0] [887.2]

Dr Wong:             Welcome to the monthly podcast, "On The Beat, for Circulation: Arrhythmia, and Electrophysiology." I'm doctor Paul Wong, editor in chief, with some of the key highlights from this month's issue. We'll also here from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                 In our first article, Mathew Daly and associates examine whether a high-resolution, 9 French, infrared thermography catheter can continuously image esophageal temperatures during atrial fibrillation catheter ablation. The infrared temperature catheter was inserted nasally or orally into the esophagus, adjacent to the left atrium. Endoscopy was performed within 24 hours to document esophageal injury. Thermal imaging showed that 10 out of 16 patients experienced one or more events where the peak esophageal temperature was greater than 40 degrees centigrade. Three patients experienced temperatures greater than 50 degrees centigrade and one experienced greater than 60 degrees centigrade. Analysis of temperature data from each subject's maximal thermal event revealed high radius, 2.3 degrees centigrade per millimeter and rates of change 1.5 degrees centigrade per second, with an average length of esophageal involvement of 11.0 millimeters.                                 Endoscopy identified three distinct thermal lesions, all in patients with temperatures greater than 50 degrees centigrade, all resolving within two weeks. The authors concluded that infrared thermography, high-resolution mapping of esophageal temperatures during catheter ablation may be performed. Esophageal thermal injury occurs with temperatures greater than 50 degrees centigrade, and was associated with large spacial-temporal gradients.                                 In our next article, Nitesh Sood and associates reported on the real-world incidence and predictors of perioperative complications in transvenous lead extractions involving ICD leads in the NCDR ICD registry. Lead extraction was defined as removal of leads implanted for greater than one year. Predictors of major perioperative complication for all extraction procedures, 11,304, and for high voltage leads, 8,362, or 74% across 762 centers were analyzed, using univariate and multivariate logistic regression. Major complications occurred in 258, or 2.3% of the extraction procedures. Of these, 258 procedures with a complication, 41 or 16% required urgent cardiac surgery. Of these, 14 or 34% died during surgery. Among the total 98, or 0.9% deaths reported, 18 or 0.16% of the total occurred during extraction.                                 In multivariate, logistic regression analysis of all extractions, female sex, admission other than electively for the procedure, three or more leads extracted, longer implant duration, dislodgement of other leads, patients' clinical status, requiring lead extraction, such as infection or perforation, were associated with increased risk of complications. For high voltage leads, smaller lead diameter, a flat versus round coil shape, in greater proximal surface coil area, were multivariate predictors of major perioperative complications.                                 The rate of major complications and mortality with transvenous lead extraction is similar in the real world compared to single center studies from high volume centers. There remains a significant risk of urgent cardiac surgery with a very high mortality, and planning for appropriate cardiothoracic surgical backup is imperative.                                 In our next paper, Bence Hegyi and associates, have reported on the repolarization reserve in failing rabbit ventricular myocytes, and the role of calcium and beta-adrenergic effects on delayed and inward rectifier potassium currents. The authors measured the major potassium currents, IKr, IKs, IK1, and their calcium and beta-adrenergic dependence in rabbit ventricular myocytes, in chronic pressure, in volume overload, induced heart failure, and compared them to age-matched controls.                                 The authors made a number of observations. One, action potential duration was significantly prolonged only at lower pacing rates, 0.2 to 1 Hertz, in heart failure under physiological ionic conditions and temperature. Two, beat to beat variability of action potential duration was also significantly increased in heart failure. Three, both IKr and IKs were significantly regulated in heart failure under action potential clamp but only when cytosolic calcium was not buffered. Four, CaMKII inhibition abolished IKs upregulation in heart failure, but did not affect IKr. Five, IKs response to beta-adrenergic stimulation was also significantly diminished in heart failure, and, six, IK1 was also decreased in heart failure regardless of calcium buffering, CaMKII inhibition or beta-adrenergic stimulation.                                 These observations changed when cytosolic calcium was buffered. The action potential prolongation in heart failure was also significant in higher pacing rates. The authors concluded that in heart failure, calcium dependent up regulation of IKr and IKs counter-balances the reduced IK1, maintaining the repolarization reserve, especially at higher heart rates. In physiologic conditions, unlike conditions of strong cytosolic calcium buffering. Under beta-adrenergic stimulation, reduced IKs responsiveness, severely limits the integrated repolarizing potassium current in repolarization reserve in heart failure, increasing the arrhythmia propensity.                                 In the next paper, Christopher Piorkowski and associates report on the feasibility of a combined endo-epicardial catheter approach for mapping the ablation of atrial fibrillation. The authors studied 59 patients with permanents pulmonary veins isolation and had further symptomatic recurrences of paroxysmal atrial fibrillation, persistent atrial fibrillation, or atrial tachycardia. These patients underwent repeat ablation using bi-atrial endo- and epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. In all patients, endo-epicardial mapping ablation were feasible using standard technologies of catheter access, three dimensional mapping, and radiofrequency ablation.                                 Epicardial mapping and ablation did not add procedural risk. Exclusively, epicardial low voltage substrate were found in 14% of patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human patients, 19% of the cohort. Epicardial ablation was needed in 80% of the patients. Over 23 months of follow up, freedom from arrhythmia recurrence was 73%. The authors used continuous monitoring and three months blanking period. Freedom from ATR of greater than two minutes was defined as the primary end-point.                                 The authors concluded that endo-epicardial mapping ablation was feasible and safe. Epicardial ablation increases transient mortality of ablation lesions. Further studies will be needed to demonstrate reproducibility and long-term outcomes, and how the technique compares to other methods.                                 In the next article, Michael Wolf and associates examined the long-term results of substrate modification for ablation of ventricular tachycardia using substrate elimination, targeting local, abnormal ventricular activities, or LAVA, post-myocardial infarction. They reported on 159 consecutive patients undergoing first ablation, age 65, 92% with ICDs, 54% with storms, and 73% with appropriate shocks. LAVA were identified in 92% and VT was inducible in 73%. Complete LAVA elimination after ablation was achieved in 64% and non-inducibility was achieved in 85%. During a median follow-up of 47 months, single procedure, ventricular free survival was 55%, 10% storms, and 19% shocks. The ventricular arrhythmia free survival was 73% after one year and 49% after five years.                                 Complete LAVA elimination was associated with improved outcomes, ventricular arrhythmia free survival of 82% at one year and 61% at five years. The subgroup treated with multi-electrode mapping and real-time image integration had improved ventricular arrhythmia free survival, 86% at one year and 65% at four years. Repeat procedures were also performed in 18% of patients. The outcomes improved, 69% ventricular arrhythmia free survival during a median follow-up of 46 months.                                 In a single center study, substrate modification, targeting LAVA for post myocardial infarction ventricular tachycardia resulted in a substantial reduction in ventricular tachycardia storm and ICDs shocks with up to 49% of patients free of arrhythmias at five years after a single procedure. Complete LAVA elimination, multi-electrode mapping, and real-time integration were associated with improved ventricular arrhythmia free survival.                                 In the next paper, Jean-Baptiste Gourraud and associates examined the safety and feasibility of transvenous lead extraction in adults with congenital heart disease over a 20 year period at a single center. The authors reported on 71 transvenous lead extraction procedures in 49 patients with adult congenital heart disease, mean age 38 years in which a total of 121 leads were extracted. The primary indication for extraction were infection in 48%, lead failure in 31%. A laser sheath was required in 46% and a femoral approach in 8%. Complete transvenous lead extraction was achieved in 92% of the leads. 49% of the patients had transposition of the great arteries. In multivariate analysis, lead duration was predictive of transvenous lead extraction failure. No perioperative death or pericardial effusion was observed. Subpulmonary, atrioventricular valve regurgitation increased in eight patients, five of whom had TGA and were independently associated with ICD leak or valvular vegetation.                                 After a median of 54 months of follow up after the first lead extraction, three deaths occurred independently from lead management. The authors concluded that despite complex anatomical issues, transvenous lead extraction can be achieved successfully in most adult congenital heart disease patients using advanced extraction techniques. Subpulmonary AV valve regurgitation is a prevalent complication, particularly in patients with transposition of the great arteries.                                 In the next paper, Gabriela Orgeron and associates examined the incidence of ventricular arrhythmias and follow-up in ARVC patients grouped by the level of indication for ICD placement, based on the 2015 International Task Force Consensus Statement Risk Stratification Algorithms for ICD Placement in arrhythmogenic right ventricular dysplasia/cardiomyopathy. In 365 of arrhythmogenic right ventricular dysplasia/cardiomyopathy patients, the authors found that the algorithm accurately differentiates survival from any sustained VT/VF among the four risk groups, p < 0.001. Patients with a Class I indication had significantly worst survival from VT/VF than patients with a Class IIa indication or a Class IIb. However, the algorithm did not differentiate survival free from VF or V flutter between patients with Class I and Class II indications. Adding Colter results, less than 100 PVCs per 24 hours to the classification, helps differentiate the risk.                                 Patients with a high PVCs burden, greater than 1000 PCVs per 24 hours had a poor survival from both VT/VF and VF and V flutter.                                 In the next paper, Takeshi Kitamura and associates studied eight patients that had bi-atrial tachycardia, a rare form of atrial macroreentrant tachycardia, in which both atria form a critical part of the circuit and were mapped using an automatic, high resolution, mapping system. 708 patients had a history of persistent atrial fibrillation, including septal or anterior left atrial ablation before developing bi-atrial tachycardia. One of the patients had a history of atrial septal path closure with a massively enlarged right atrium. The authors found that 9 atrial tachycardias, with a median cycle length of 334 milliseconds had three different types. Three were peri-mitral and peri-tricuspid reentrant circuit, three utilized the right atrial septum in a peri-mitral circuit, and three utilized only the left atrium and the left right atrial septum.                                 Catheter ablation successfully terminated eight of the nine bi-atrial tachycardias. The authors found that all patients who developed bi-atrial tachycardia had an electrical obstacle on the intraseptal left atrium, primarily from prior ablation lesions.                                 In our next paper, Kwang-No Lee and associates randomized 500 patients with paroxysmal atrial fibrillation to one of two strategies after pulmonary vein isolation. One, elimination of non-PV triggers in 250 patients, group A, or, two, step-wise substrate modification using complex fractionated atrial electrogram or linear ablation until non-inducibility of atrial tachyarrhythmias was achieved, 250 patients in group B. Recurrence of atrial tachyarrhythmias was higher in group B compared to group A. 32% of patients in group A experienced at least one episode of recurrent atrial tachyarrhythmia after the single procedure, compared to 43.8% in group B. P-value of 0.012 after a median follow-up of 26 months. Competing risk analysis showed that the cumulative incidence of atrial tachycardia was significantly higher in group B compared to group A (p= 0.007).                                 The authors concluded that elimination triggers as the end-point of ablation in paroxysmal atrial fibrillation patients decreased long-term recurrence of atrial tachyarrhythmias compare to non-inducibility approach achieved by additional empiric ablation.                                 In our final paper of the month, Roland Tilz and associates reported on 10 year outcome after circumferential pulmonary vein isolation using a double lasso and three dimensional electro anatomic mapping technique. From 2003 to 2004, 161 patients with symptomatic drug refractory paroxysmal atrial fibrillation underwent electro-anatomical mapping guided circumferential pulmonary vein isolation. The procedure end-point was absence of pulmonary vein spikes thirty minutes after isolation, after a single procedure and a median follow up of 129 months, stable sinus rhythm was present in 32.9% of patients based on Holter-ECGs and telephonic interviews. After multiple procedures, mean 1.73 and median follow up of 123.4 months, stable sinus rhythm was seen in 62.7% of patients. Progression towards persistent atrial fibrillation was observed in 6.2%.                                 The authors concluded that although the 10-year single procedure outcome in patients with paroxysmal atrial fibrillation was low, 32.9%, it increased to 62.7% after multiple procedures and the progression rate to persistent atrial fibrillation was remarkably low.                                 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. Dr Kapa:               Thank you Paul, and welcome back everybody to Circulation’s “On the Beat”, where we'll be discussing hard hitting articles across the electrophysiology literature.                                 Today, we'll be reviewing 22 separate articles of particular interest, published in January 2018. The new year saw plenty of articles that are of particular interest either for the future of our field of for present management of our patients. First, within the realm of atrial fibrillation, we'll review several articles within the realm of anticoagulation and left atrial appendage occlusion.                                 The first article we'll review is by Yong et al in the American Heart Journal, volume 195, entitled "Association of insurance type with receipt of oral anticoagulation in insured patients with atrial fibrillation: A report from the American College of Cardiology NCDR PINNACLE registry." In this publication, the author sought to evaluate the effect of insurance type on the appropriate receipt of anticoagulant therapy, specifically looking at warfarin versus NOACs. They reviewed retrospectively over 360,000 patients and found significant differences in appropriate prescription of anticoagulants, irrespective of which anticoagulant was considered. Medicaid patients received less appropriate anticoagulant prescription than those who were privately insured on Medicare or military insured. Furthermore, those on military or private insurances had a higher rate of NOAC prescription than those with Medicare.                                 Furthermore, there was an even wider disparity in NOAC use than warfarin use amongst differently insured patients. These data are important in that they highlight potential variability in appropriate management of patients based on insurance type. Of course, there are many issues that might impact this, such as health care access or available pharmacy coverage of specific medications. Furthermore, the authors do not dive into the impact on outcomes based on the therapy availability.                                 The next article we'll review is by Jazayeri et al, entitled "Safety profiles of percutaneous left atrial appendage closure and lysis: An analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016" published in the Journal of Cardiovascular Electrophysiology in volume 29 issue 1. Here, the authors sought to evaluate the overall safety profiles of procedures performed with different percutaneous left atrial appendage occlusion devices, including LARIAT and WATCHMAN. They review 356 unique reports and compared outcomes pre- and post- approval of the WATCHMAN device. The look at the specific composite outcome of stroke, TIA, pericardiocentesis, cardiac surgery, and death. They noted that this composite outcome occurred more frequently with WATCHMAN than with LARIATs, and this is irrespective of pre- or post- approval status.                                 These findings highlight the importance of postoperative monitoring in evaluation of overall outcomes. The reason by which there was more frequent negative outcomes in the WATCHMAN than LARIATs need to be considered. Obviously there's several limitations in the MAUDE database, similar with all large databases. However, it does highlight the importance of considering the mechanisms or sure decision making necessary, not just amongst patients and their providers but amongst operators of the staff or amongst physicians and industry executives. To determine how to optimize devices going forward.                                 Speak of left atrial appendage occlusion devices and the potential future of these, we next review an article by Robinson et al, entitled "Patient-specific design of a soft occluder for the left atrial appendage" published in nature biomedical engineering, in volume two in the year 2018. Robinson et al used 3D printing to create a soft, immunocompatible, biocompatible, endocardial implant to occlude the left atrial appendage. They use the individual CT of an in vivo pig to three D print using a specialized material, a left atrial appendage occlusion device, and demonstrated feasibility of achieving adequate occlusion. This paper is important and is one of the initial [inaudible 00:22:03] to how three D printing may be used to optimize patient care. In fact, three D printing has the potential to overturn medical manufacturing and device development.                                 Anatomy tends to be more often patient-specific than not. That's one size fits all implant designs may not be optimal, and resulting exclusion or inadequate occlusion amongst many patients. Decide of three D printable patient specific rapidly prototype soft devices that are biocompatible and hemocompatible, holds the potential to revolutionize the occlusion.                                 Staying in the field of left atrial appendage occlusion, we next review an article by Lakkireddy et al entitled "left atrial appendage closure and systemic homeostasis: The LAA homeostasis study" published in JACC. The authors sought to evaluate the effect of epicardial-versus endocardial left atrial appendage occlusion on systemic homeostasis, including effects on neuro-hormonal profiles of patients. They performed a prospective, single center, observational study, including 77 patients, about half of whom received endocardial versus epicardial device. Interestingly, they noted that the epicardial left atrial appendage occlusion cohort exhibited significant decrease in blood adrenaline, noradrenaline and aldosterone levels. Those are not seen with endocardial devices. Internal epicardial devices are associated with increases in adiponectin and insulin levels as well as a decrease in free fatty acids and consistently lower systemic blood pressure.                                 These data suggest a significant difference in the effect of epicardial versus endocardial closure left atrial appendage on neurohormonal profile. The authors propose several mechanisms for these findings but not the exact mechanisms as yet unclear. Several factors potentially could lead to these findings. One is that epicardial ligation may result in more total ischemia of the left atrial appendage than endocardial closure. Another potential mechanism maybe that the presence for material in the pericardial space versus in the bloodstream may have different effects on neuro-hormonal profile. However, these significant differences in outcomes highlight the importance of considering whether all approaches of left atrial appendage occlusion are considered equal. Many flaws of this study is that it's observational and not randomized. Does it possible those receiving epicardial closure may have been perceived to be lower risk for epicardial puncture, in this, as result, had better long-term outcomes.                                 Changing gears now but staying within the realm of atrial fibrillation, we next review elements for cardiac mapping and ablation. The first article we review is one that has received significant press, published by Marrouche et al entitled "Catheter ablation for atrial fibrillation with heart failure" in the New England Journal of Medicine, volume 378. It is well recognized that morbidity and mortality are higher in heart failure patients who also have atrial fibrillation. Marrouche et al published the results of the CASTLE-AF trial, which attempted to determine if catheter ablation [inaudible 00:24:46] better outcomes among patients with heart failure and atrial fibrillation. They randomized 179 patients to ablation and 184 to medical therapy, which consisted of either rate or rhythm control. Inclusion criteria were those with NYHA class II to IV heart failure, LVEF of 35% or less, and an ICD.                                 The primary endpoint was a composite where the death from many causes or hospitalizations for worsening heart failure. They noted over a median of three as a follow up, the end-point was reached in 28.5% of the ablation group and 44.6% of the medical therapy group, accounting for a significant hazard ratio of 0.62. Furthermore, fewer patients that in the ablation group died from any cause, were hospitalized for worsening heart failure, or died from cardiac causes. These data made a big splash because they're highly supportive of the premise that catheter ablation may be beneficial in some patients with atrial fibrillation and heart failure, often beyond that of medical therapy alone.                                 One major strength of this paper is that the actual AF burden was tracked by the ICD, so we know for sure whether or not the procedure was successful and how controlled the atrial fibrillation was. One thing to note however, is that subgroup analysis suggest that those with more symptomatic heart failure, namely NYHA class III to IV, not benefit as much from ablation. Furthermore, it's also important to note that the five years expected mortality in patients was higher than predicted in the CASTLE-AF trial, however overall these trials highly suggest that the potential benefit that ablation may hold over conventional medical therapy. Extrapolation to comparison with the utility of interventions such as biventricular pace with AV node ablation, however, remains to be considered.                                 Next, we review an article by Chugh et al entitled "Spectrum of atrial arrhythmias using ligament of Marshall in patients with atrial fibrillation" published in Heart Rhythm volume 15, issue 1. They reviewed the spectrum of presentations associated with arrhythmogenesis attributed to the ligament of Marshall, amongst patients with atrial fibrillation. They demonstrate that nearly a third of those patients, ligament of Marshall associated arrhythmias had a pulmonary vein ligament connection, that variously required ablation, the left lateral ridge, the mitral annulus, or alcohol ablation. In addition, they noted about a quarter of patients had atrial tachycardia attributable to the ligament, and the remaining had periatrial reentry requiring either ablation or alcohol injection of the ligament to attain a conduction block.                                 The relevance of this publication, albeit it is of a small number of patients and a small center, lies in highlighting on the right mechanisms by which the ligament of Marshall may contribute to arrhythmogenesis. Namely, can include direct venous connections, inhibition to inaudibility to attain mitral block, and directly attributed atrial arrhythmias. Recognition of the various ways and situations under which the ligament of Marshall may play a role in arrhythmogenesis in atrial fibrillation patients, may optimize physician decisions to look for identify and target the ligaments. What is not as well understood however is the frequency with which ligament of Marshall plays a significant role in arrhythmogenesis in atrial fibrillation.                                 Moving gears, we next review an article by Pathik et al entitled "Transient rotor activity during prolonged three-dimensional phase mapping in human persistent atrial fibrillation" published in a special issue of JACC Clinical Electrophysiology, that focus on atrial fibrillation specifically, in volume 4 issue 1. Pathik et al sought to validate three-dimensional phase mapping system for persistent atrial fibrillation. Commercially available rotor mapping systems project the heart into two dimensions based on a three-dimensional catheter. Instead, Pathik et al used a combination of basket catheters along with the non-left atrial surface geometry to construct three D representations of phase progression. Amongst 9 out of 14 patients, they identified 34 rotors, with all these rotors being transients. Of particular interest, the rotors were only seen in areas of high electric density, where internal electric distances were shorter. They also noted the single wave front is also the most common propagation pattern. The importance of this publication lies in considering two things. First is the three dimensional representation of rotor position and the feasibility of this, and the second is really the high electro-density necessary to observe for others.                                 This has been one of the main problems in rotor analysis, namely what the spacial and temporal density is, that is required to identify rotors, especially given how transient they often are. The presence of rotors does not necessarily mean they're ablation targets in all patients. However, the question still remains regarding the optimal approach to mapping rotors, it needs to be remembered that rotors actually are meant to represent three dimensional scrollway phenomena, that cannot necessarily always be reflected in traditional two D mapping schema. Furthermore, to be remembered that when we claim three-dimensional mapping, this just reflects a two-dimensional surface being wrapped in three dimensions to reflect overall internal surface geometry but it does not take into account transmural activation.                                 Thus, taking into account all these elements it should be remembered as sometimes, it is possible that a rotor might exist but it's just not evident based on the two-dimensional representation or a two-dimensional representation that looks like a rotor may in fact not be a rotor when you consider it in a three-dimensional media.                                 Our last article within the realm of cardiac mapping and ablation we will consider is by Zghaib et al, entitled "Multimodal examination of atrial fibrillation substrate: Correlation of left atrial bipolar voltage using multielectrode fast automated mapping, point by point mapping, and magnetic resonance imaging intensity ratio", published in JACC Clinical Electrophysiology, in the same volume as the previous article. The authors sought to compare fast automated mapping with multiple electrodes versus point by point mapping and correlate with weighed gadolinium enhancement as seen by MRI, termed the image intensity ratio.                                 We all recognize that bipolar voltage is critical to recognizing and evaluating substrate. It's traditionally used in decay regions of substrate in both the atrium and ventricles. However, whether a newer automated approach used to characterize substrate perform equally well in comparison with traditional point to point mapping is still unknown. Thus, the authors in 26 patients perform cardiac MRI and mapping endocardial using both voltage mapping techniques. They noted that for each unit increase in image intensity ratio on MRI, in other words, increasing late enhancement, there was 57% reduction of bipolar voltage. They also noted that the bipolar voltage using other fast elevating mapping or point by point was significantly related with actual differences in calculated voltage, becoming more dissimilar in the extreme of high and low voltage areas.                                 The relevance of this publication is highlight in the potential utility of fast automated mapping in creating accurate voltage maps. The correlation of voltage values with image-intensity ratios suggest the utility of either approach. In turn, correlation with MRI suggest a pathologic correlate for all of these findings. However, whether substrate characterization guide ablation carries incremental benefit remains to be seen.                                 Changing gears but staying in the realm of atrial fibrillation, we next review elements of risk stratification and management. The first article we review is by Friedman et al, entitled "Association of left atrial appendage occlusion and readmission for thromboembolism amongst patients with atrial fibrillation undergoing concomitant cardiac surgery", published in JAMA, volume 319, issue four. Friedman et al sought to evaluate whether surgical left atrial appendage occlusion let to a reduction in long-term thromboembolic risk in a large database of Medicare recipients. They included the primary outcome as readmission for thromboembolism, including stroke, TIA, or systemic embolism, in up to three years of follow-up. With secondary end-points including hemorrhagic stroke, all-cause mortality, and a composite end-point of all outcomes.                                 Amongst more than 10,000 patients, there were almost 4,000 patients receiving surgical occlusion of left atrial appendage. Surgical occlusion was associated with a reduction in thromboembolic risk, OR of 6%, all cause mortality, 17 versus 24%, and the composite end-point, 21 versus 29%. However, interestingly, surgical occlusion was only associated with reduction in thromboembolic risk compared with no occlusion amongst those discharged without anticoagulation and those discharge with it. Namely, the thromboembolic risk reduction was primarily seen in those where the surgical occlusion, those who were sent home without any sort of anticoagulation. These data suggest that surgical occlusion leads to reduction of thromboembolic risk overall. As any large database based study, there are massive flaws in the database itself. Namely, we're relying on the coding of hospitals and operators. To know exactly what was done and what happens latter.                                 However, these data are hypothesis generating. One key element is the fact that surgical left atrial appendage occlusion was only superior in reducing thromboembolic risk amongst those discharged without anticoagulation. This raises the question as why. Was left atrial appendage completely closed in these patients? In which case, they may be at further increased risk or that the operators felt that there is a high risk for other reasons that cannot be cleaned from an administrative datasets? While the data support consideration of the benefit of left atrial appendage occlusion in a surgical manner, a kin to what has been seen in papers on WATCHMEN and other approaches, and how is the critical nature of randomized trials in this regard.                                 We next review an article published in JAMA Cardiology, volume three issue one by Inohara et al, entitled "Association of atrial fibrillation clinical phenotypes with treatment patterns and outcomes: A multicenter registry study." Traditionally classification of AF has depended largely on factors such as the nature of AF, paroxysmal versus persistent, LA size, and other factors such as extend of the late enhancement. Inohara et al sought to evaluate whether cluster analysis could better define heterogeneity of AF in the population. They included an observational cohort of almost 10,000 patients admitted to 124 sites in the United States in the ORBIT-AF registry.                                 Outcome was a composite major address cardiovascular and neurological events or major bleeding. Amongst these patients, they identified four clusters, including one those with lower rates of risk factors and comorbidities than other clusters, two, those with AF at younger ages and with comorbid behavior disorders. Three, those with AF with tachycardia-bradycardia type syndromes and had devices for sinus node dysfunction, and four, those with AF with other risk factors such as a coronary disease. Those in the first cluster had significantly lower risks of major events. All clusters were noted to have symptom dissociation to specific clinical outcomes.                                 These data are interesting and highlight the highly heterogeneous nature of classifying risk attributable to atrial fibrillation. When broad datasets associated atrial fibrillation with specific outcomes. Maybe suggest an attribution to all patients with atrial fibrillation. However, this single relationship was specific to the outcomes suggest the limitation of applying outcome as approach to understand atrial fibrillation impacts and outcomes, namely depending on clusters that may take into account patient age or comorbidities, it may be irrelevant in discriminating patient outcomes than the traditional paradigm in the same paroxysmal versus persistent or depending on the left atrial size.                                 These data also highlight the importance of considering the inclusion criteria in randomized trials of atrial fibrillation before stripling real world outcomes to patients who don't fit within that trial.                                 Next, we will be reviewing an article by Chou et al entitled "Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation," published in JACC, volume 71 issue two. Chou et al sought to evaluate the effect of aging and evolving instant comorbidities to stroke risk in patients with atrial fibrillation. Many large database studies or trials where added baseline CHADSVASC score and the then ensuing follow up period to define risk over time of ischemic stroke.                                 The authors hypothesized that as patients age, develop new comorbidities that would change the score, may be more predictable of long-term outcomes than the score itself. They included over 31,000 patients who do not have comorbidities to CHADSVASC aside from age and sex but had atrial fibrillation. They didn't calculate a delta score defined as the difference between the baseline and follow up scores. The mean baseline score was 1.29 with an increase in 2.3 during follow up, with an average delta of one. The score may not change over follow up in 41% of patients. Interestingly, significantly more patients had a delta CHADSVASC of one or more and develop ischemic stroke than non-ischemic stroke. The delta CHADSVASC was shown to better predictor of ischemic stroke than either baseline or follow up CHADSVASC score. This data suggest that additive shifts in the CHADSVASC score over time may be more predictive of stroke risk than the actual score itself.                                 These findings are thoughtful and logical. They indicate the potential impact of continued aging or acquisition identification of new comorbidities. In some patients, potential discovery or new comorbidities or follow-up; for example, hypertension and coronary artery disease may lead to reclassification of stroke risk. That is important to maintain close follow up of atrial fibrillation patients, and not to show a continued need or lack of need of anticoagulation on the basis of a baseline evaluation. This also holds relevance single center long-term outcomes in patients specific scores. Whether is acquisition of new comorbidities or presence of baseline comorbidities or predict a long-term score, should we consider when assessing the need for anticoagulation, particularly in perceived initially low risk cohorts who go on to develop ischemic stroke.                                 Lastly, within the realm of atrial fibrillation, we review an article by Hussain et al, entitled "Impact of cardiorespiratory fitness on frequency of atrial fibrillation, stroke, and all-cause mortality" published in the American Journal of Cardiology, volume 121 issue one. Hussain et al review the effect of cardiorespiratory fitness on overall outcomes and incidence of atrial fibrillation and outcomes amongst patients with atrial fibrillation. Amongst over 12,000 individuals prospectively followed up after treadmill exercise test, they noted 1,222 had a incidence of AF, 1,128 developed stroke, and 1,580 died. For every 10% increase in functional layover capacity, there was a 7% decrease in risk of incident AF, stroke, or death.                                 Similarly, in those who developed AF, stroke was lower in those with higher functional aerobic capacity. These findings support the notion known to other areas of cardiovascular disease that better cardiorespiratory fitness is associated with better outcomes, in this case to stroke, incident AF, or mortality. Furthermore, even on the presence of AF, those with better functional capacity had a lower risk of stroke. These data highlight the continued importance of counseling patients on the benefits of physical fitness even in the setting of already present AF.                                 Moving on to a different area of electrophysiology, we review the realm of ICD pacemakers and the CRT.                                 The first article review is by Sze et al entitled "Impaired recovery of left ventricular function in patients with cardiomyopathy and left bundle branch block" published in JACC volume 71 issue 3. Patients with left bundle branch block and cardiomyopathy are known to respond to CRT therapy. Thus the investigators sought to evaluate whether guideline medical therapy in patients with reduced LVEF and left bundle branch block, afford a beneficial first line approach therapy. The reason for this currently guidelines suggest waiting at least three months before consideration of CRT has had as some patients may recover on guideline directed medical therapy without the need for device implantation.                                 They review patients with a LVEF of less or equal than 35% and baseline ECG showing left bundle branch block. In evaluating left ventricular ejection fraction at follow up of three to six months. They excluded patients with severe valvular disease, and already present cardiac device, an LVAD, or heart transplant. Among 659 patients meeting criteria, they notice 74% had a narrow QRS duration of less than 120 whereas 17% had QRS duration greater than 120, and the remainder had a QRS duration greater 120 but was not left bundle branch block. The mean increase in the left ventricular ejection fraction on guideline directed medical therapy was in those with a narrow QRS duration and least in those with left bundle branch block, 8.2%.                                 Furthermore, when comparing mean LVEF improvement, those with on versus non-on guideline directed medical therapy, there was virtually no difference in rates of recovery. Furthermore, composite end-point of heart failure hospitalization mortality was highest in those with left bundle branch block. These data suggest that those with bundle branch block and cardiomyopathy received less overall benefit from guideline directed medical therapy over the three to six months follow up period. Whether this is due to already more severe myopathic process to start with or due to the CRT is unclear. However, it may suggest that in some patients, left bundle branch block may benefit from inclusion of CRT early in their disease course as known the significant number of patients up to three to six months guideline directed medical therapy with insufficient DF recovery may then benefit from CRT. As well as intervening earlier may result in better outcomes, especially knowing the high and term raise mortality in heart failure hospitalization remains to be seen.                                 A trial studying early implantation of CRT on these patients may be relevant.                                 The next article review is by Gierula et al entitle "Rate-response programming tailored to the force-frequency relationship improves exercise tolerance in chronic heart failure" published in JACC Heart Failure, in volume six, issue two. The authors sought to evaluate whether tailored rate-response programming improved exercise tolerance in chronic heart failure. The double blinded, randomized, control, crossover study, they compared the effects of tailored programming on the basis of calculated force-frequency relationship, defined as including critical heart rate, peak contractility, and the slope, multidimensional programming and exercise time and maximal oxygen consumption. They demonstrate amongst 98 enrolled patients that rate-response settings limiting heart rate raise to below the critical heart rate led to create exercise timing and higher peak oxygen consumption.                                 These data suggest that personalizing rate-response therapies may improve exercise time and oxygen consumption values in patients with heart failure and pacing devices. The main limitation of the study is that the number of patients was small, 90, and then the number of patients crossing over was even smaller, 52. However, highlights the potential of working closely between device programmers and consideration of individual's characteristics and their exercise needs in determining optimal programming strategy.                                 Finally, within the realm of devices, we review an article by Hawkins et al, entitled "Long-term complications, reoperations, and survival following cardioverter defibrillator implant" published in Heart, volume 104 issue three. Hawkins et al sought to evaluate the long-term complications and risk of reoperation associated with defibrillator implantations in a large [inaudible 00:41:56] population of 300,410 patients, they noted over a 30-month follow up period there was a 12% reoperation rate within the year of implant. This is most prominent for CRT devices, with a risk of 18% in one year post-implant. Furthermore, CRT had the highest rate of early complications, with device complexity, age, or the presence of atrial fibrillation being significantly associated with complication risk.                                 Mortality also increased over time from 5% within the first year to nearly a third after five years. However, younger patients exhibited five years survival similar to the general population with a progressive decline of this as older patients were considered. These findings highlight several critical issues. First, they report a high one year reoperation rate for a variety of reasons. This finding highlights the importance of considering protocols to minimize the need for reoperation. Furthermore, they note the higher rate amongst CRT patients, with seems logical given the likely longer associated procedural risk and need for more leads. Finally, the impact of age on expectant survival are to be taken into consideration with the device and the life-saving potential of the defibrillator.                                 Moving on to cellular electrophysiology, review one article by Zhang et al, entitled "Reduced N-type calcium channels in atrioventricular ganglion neuron are involved in ventricular arrhythmogenesis" published at the journal of the American Heart Association, in volume seven issue two. Zhang et al reported a rat model of ventricular arrhythmogenesis and characterized the role of atrioventricular ganglion neurons in risk of arrhythmogenesis as well as the mechanism for this risk this model relates in humans to the attenuated cardiac vagal activity in heart failure patients, which is known to relate to their arrhythmic risk. The demonstrated reduced N-type calcium channel in these AV ganglion neurons, which project innervating systems to the myocardium, resulting in increased risk of PVCs, and increased susceptibility to induction of ventricular arrhythmias with programmed stimulation.                                 The relevance of the intrinsic cardiac nervous system arrhythmogenesis has become increasingly prominent as methods to study it have improved. Understanding the direct and most relevant inputs may facilitate better understanding of risk of arrhythmias in patients. In the case of this study by Zhang et al, the critical finding is that disorder of the atrioventricular ganglion neurons may lead to increased susceptibility for ventricular arrhythmogenesis. Clinical relevance includes consideration of effects on this specific ganglion when performing ablation on for other conditions, and potential long-term effect on arrhythmogenic risk, as well as potentially relevant functional explanations for arrhythmogenesis.                                 Moving on to the genetic channelop, these are considered two separate articles. The first one by Bilmayer et al, entitled "ExomeChip-Wide analysis of 95,626 individuals identified ten novel loci associated QT and JT intervals" published in Circulation: Genomic and Precision Medicine, in volume 11 issue 1. This whole exome study reviewed several novel loci that modified the QT and JT intervals. They include over 100,000 individuals and identified ten novel loci not previously reported in the literature. This increases the number of known loci that impact from ventricular portal adjacent by nearly one third. These loci appear to be responsible for myocyte and channel structure and interconnections that internally impact the ventricular repolarization.                                 While long QT syndrome be characterized amongst the known genes in 75% of affected individuals, that also means one fourth long QT syndrome cannot be characterized based on known genes impacting ventricular repolarization. The identification of novel loci or novel that may be affect repolarization kinetics to unique means are critical to define novel therapies as well as in genetic counseling the patients in potential effects on family members when screening them for potential disease risk. These findings should assess an opportunity for further studying the mechanisms by which these loci modulate QT and JT intervals and the potential contribution to phenotypic risk.                                 The second paper within this realm we review is by Zumhagen et al, entitled "Impact of presynaptic sympathetic imbalance on long QT syndrome by positron emission tomography" published in Heart, volume 104. The authors sought to evaluate by a PET scan the impact of sympathetic heterogeneity on long-QT syndrome risk. Amongst 25 patients with long-QT syndrome, including long-QT type I and II, and 20 ostensibly healthy controls, they noted that regional retention in disease were similar between affected patients and controls. However, regional washout rates were higher in the lateral left ventricles in patients with long-QT syndrome. Internal global washout rates were associated with greater frequency of clinical symptoms. That's there seem to be some relationship between regional and global sympathetic heterogeneity, particularly during washout, with overall risk in long-QT syndrome patients.                                 These findings report the notion for sympathetic imbalance, partly mediating the risk attributable to long-QT syndrome. The findings on PET suggest regional imbalance of presynaptic cathecholamine and reuptake and release, being one mechanisms. This was most prominent in long-QT I patients who also often drive most benefit from left sided sympathectomy. The novelty of these findings is in the potential role of imaging to determine basic contributors to congenital long-QT syndrome in given patients. The larger prospect of size would really need to be evaluated this further.                                 Moving on to the realm of ventricular arrhythmias, we review three different articles. The first one, by Hamon et al, entitled "Circadian variability patterns predict and guide premature ventricular contraction ablation, procedural disability, and outcomes" published in Heart Rhythm, volume 15 issue one. Hamon et al sought to evaluate whether circadian variability of PVC frequency can predict optimal drug response intraprocedurally during PVC ablation. One of the main problems of PVC ablation is when PVC are infrequent and tend to disappear during the procedure, achieving procedural success or attaining sufficient frequencies of PVCs to map becomes very difficult. Next, they use Holter monitoring in the ambulatory stripe to define three groups. Those of higher PVC burden during faster heart rates, those with higher PVC burden during slower heart rates, and those with no correlation between their PVCs burden and their heart rate.                                 More than half the one hundred and one patients included a high burden of PVCs at fast rate while 40% had no correlation between the two and 10% had higher burden in slower heart rates. Almost one third of patients taken for ablation have infrequent PVCs during a procedure, while the best predictor of this being a low ambulatory PVC burden of less than 120 per hour. Isoproterenol infusion was only useful in lessening PVCs in those with PVCs associated with fast heart rates. The isoproterenol washout or phenylephrine where used with those associated with slower heart rates.                                 Interestingly, not a single drug was effective in inducing PVCs in those with infrequent PVCs that have not heart rate correlation in the ambulatory stages. They noted that outcomes ablates were similar amongst those with higher heart rate associated PVCs and non-heart rate correlated PVCs previously responded to a drug. But, [inaudible 00:48:08] noted only a 15% success rate from ablation in infrequent PVCs in patients who lacked correlation between PVC burden and heart rate and who were unresponsive to drug previously. These data are important highlighting the potential for further defining idiopathic PVC ablation needs and likelihood of success based on ambulatory data, by correlating PVC burden with heart rate and their circadian variability, it's possible to predict likelihood specific intraoperative drugs working when dealing with infrequent intraprocedural PVCs.                                 Furthermore, the finding of lack of correlation with slower or fast heart rate in terms of PVC burden is associated with the poor success rate unless those PVCs are drug responsive. Highlights the potential benefit of performing preoperative antiarrhythmic drug testing to get likelihood of ablation success in this patients.                                 The next article we review is by Lee et al, entitled "Incidence and significance of the lesions encountered during epicardial mapping and ablation of ventricular tachycardia in patients with no history of prior cardiac surgery or pericarditis" published in Heart Rhythm, volume 15 issue one. Lee et al sought to determine the frequency of pericardial lesions, impeding mapping in patients without prior surgery, operative procedure, or pericarditis, in other words virgin hearts. Amongst 155 first time attempts of access, 8% had pericardial lesions. The only clinical predictor was the presence of severe renal impairment.                                 In addition, no patients with supposedly normal hearts had a lesions. Notably, those with a lesion had more frequent impairment in mapping and lower overall success rates; there were similar complication rates as those without the lesions. These data are relevant in highlighting the ease of mapping of pericardial access may not always be present, even when dealing with inversion of pericardial space. A lesion may be present in patients, particularly with severe renal disease. Advising patients of this possibility prior to the procedure and considering that epicardial access may be impaired in a fair number of patients, even the absence of prior history of surgery, epicardial access or pericarditis isn't important.                                 The final article we'll review within the realm of ventricular arrhythmias is by Kumar et al, published in Journal of Cardiovascular Electrophysiology, volume 29 issue one, entitled "Right ventricular scar-related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics, mapping, and ablation underlying heart disease." Kumar et al sought to evaluate the substrate and outcomes associated with right ventricle scar related ventricular tachycardia ablation in nonischemic patients at large, but particularly in those with neither stroke or coronary artery disease as potential explanations for this scar. They reviewed 100 patients consecutively over half of whom had ARVC and the remainder was sarcoid or RV scar of unclear origin. Those with RV scar of unknown origin tend to be older compared to the ARVC patients, and had more severe LV dysfunction compared with saroid patients.                                 However, the scar distribution extend was similar within all these groups. Furthermore VT/VF survival was higher in those with RV scar of unknown origin. The velocity of survival free or death or cardiac transplant and VT/VF survival seen in sarcoid patients. These data suggest that close to one third of patients, RV scar related VT may have VT of unknown cause. Total outcome was superior overall to those with defined myopathic processes. What's most interesting is, over follow up, none of those with RV scar of unknown origin develop any further findings to reclassify them as sarcoid or ARVC. It is possible this group reflects some mild form of either disease however. Again, the exact pathophysiologic process remains unclear. These findings may help in counseling patients who are in long-term expected outcomes from ablation intervention.                                 The final article we'll review this month is within the realm of other EP concepts that may be broadly applicable, published by van Es et al, entitled "Novel methods for electrotissue contact measurement with multielectrode catheters", published in Europace, volume 20 issue one. In this publication, the authors sought to evaluate the potential utility of a novel measure on evaluating electro tissue contact. With multielectrode catheters it is known that one of the problems with assessing contact is a contact force that cannot be used. Electro with coupling index is often used but even this has fragile problems, especially when you get into high impedance areas, that can be affected by surrounding ion impedance structures. Due to the fact that measuring contacts forces challenging in such multielectrode catheters, the authors measure electric interface resistance by applying a low level electrical field, pushing neighboring electrodes. They compared the effectiveness of assessing contact by this approach without using contact force in a poor side model.                                 They know that this measure was directly correlated with contact force in measuring tissue contacts. These findings support a role for aversion of an active electrode location and determining tissue proximity and contact-based on the coupling between the electrodes on multipolar catheters in the tissue. These findings may be highly useful when there is a variety of catheters where contact force cannot be implemented. Further studies on the methods and cutoff to establish tissue proximity on the end of contact will be also needed.                                 To summarize, however, as a term was brilliant here that was not well explained, active electrical location is actually a phenomenon that occurs in nature. This is seen in deep sea fish, which actually have multiple electrodes oriented around its body. They emit a small electrical field that results in a general impedance field surrounding the fish. This essentially is the way of visualizing the world around them. Perturbations based on proximity to different structures, whether they are live or death, and based on whether they are live or death, results in changes in the perturbations of this resistive fields, resulting in proximity determination by the fish. Several individuals are looking into potential applications of this to understanding tissue proximity when using catheters in the body. This consideration of impedance is fundamentally different than the traditional measure impedance were used by traditional generator.                                 I appreciate everyone's attention to this key and hardening articles that we've just focus on or this past month of cardiac electrophysiology across literature. Thanks for listening. Now back to Paul. Dr Wong:             Thanks Suraj, you did a terrific job surveying all journals for the latest articles on topics of interesting in our field. There's not an easier way of staying in touch with the latest advances. These summaries and the list of all major articles in our field for month can be downloaded from the Circulation: Arrhythmia and Electrophysiology website. We hope that you find the journal to be the go to place for everyone interested in the field.                                 See you next month.  

Dr. Paul Wong:                  Welcome to the monthly podcast, On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wong, 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, Ratika Parkash and associates examined whether the outcomes following escalated antiarrhythmic drug therapy, or catheter ablation, depended on whether ventricular tachycardia with amiodarone refractory or sotalol refractory in patients with prior myocardial infarction in the VANISH study. At baseline, 169, or 65%, were amiodarone refractory, while the remaining were sotalol refractory. Amiodarone refractory patients had more renal insufficiency; 23.7% versus 10%. Worse, new ARC Heart Association class, 82.3% versus 65.5% class II or III; and lower ejection fraction, 29% versus 35%. Within the amiodarone refractory group, ablation resulted in a reduction of any ventricular arrhythmias compared to escalated drug therapy, with a hazard ratio of 0.53, P = 0.02. Sotalol refractory patients had trends towards higher mortality in VT storm with ablation, with no effect on ICD shocks. Within the escalated drug arm, amiodarone refractory patients had a higher rate of composite endpoint, with a hazard ratio of 1.94 and a P value of 0.01. In a trend toward higher mortality, hazard ratio 2.4, P = 0.07. While mortality was not different between amiodarone and sotalol refractory patients within the ablation treatment group. In our next study, Junaid Zaman and associates examined 57 cases in which local ablation of persistent atrial fibrillation terminated to sinus rhythm or organized tachycardia. The authors analyze unipolar electrograms collected during atrial fibrillation from multi-polar basket catheters to reconstruct isochronal activation maps for multiple cycles, and computational modeling and phase analysis were used to study mechanisms of map variability. At all signs of atrial fibrillation termination, localized, repetitive activation patterns were observed, 21% with complete rotational activity, 46% with partial rotational circuits, and 33% with focal patterns. In computer simulations incomplete segments of partial rotations coincided with areas of slow conduction, characterized by complex, multi-component electrograms. In our next article, Matthew Kalscheur and associates sought to use a novel machine-learning approach to predict outcomes following resynchronization therapy in the companion trial. The random forest algorithm resulted in the best performing model. In 595 CRTD patients in the companion trial, 105 deaths occurred, with a median follow-up of 15.7 months. The survival difference across subgroups differentiated by bundle branch block morphology and cure restoration did not reach significance, P = 0.08. The random forest model, however, produced quartiles of patients with an eight-fold difference in survival between those with the highest and lowest predictive probability for events, hazard ratio 7.96 with a P value of less than 0.0001. The model also discriminated the risk of composite endpoint of all cause mortality, or heart failure hospitalization, better than subgroups based on bundle branch block morphology and cure restoration. Future studies are needed to validate this model in other populations. In our next paper, Amr Barakat and associates examined the clinical outcomes of trans-venous lead extraction for CIED infection based on renal function. The authors examined 1,420 consecutive patients undergoing trans-venous lead extraction of infected CIEDs over a 14 year period. Groups with normal renal function, Group 1, consisting of 1,159 patients, Group 2, 163 patients with renal dysfunction not requiring dialysis, and Group 3, 98 patients on dialysis. Complete procedural success rates were comparable in the three groups: 94%, 96%, and 94% in Groups 1, 2 and 3, respectively. This was not statistically significant. The mortality rates were significantly higher in dialysis patients at one month. The procedure-related complication was 12.2% in dialysis patients versus 6.5% in Group 1 and 6.1% in Group 2. Other factors associated with mortality were lead material retention, functional New York Heart Association Class, and occurrence of procedural complications. In our next paper, Eric Johnson and associates studied the contribution of the current ITO, two left ventricular re-polarization in the human heart, since the current has been shown to have an important role in animal models. The authors found that using whole-cell voltage clamp recordings from myocytes, isolated from the left ventricle, non-failing human hearts, that there were two, distinct transient currents, ITO fast and ITO slow. The two currents have significantly different rates of recovery from inactivation and pharmacological sensitivities. ITO fast recovers in about 10 milliseconds, 100 times faster than ITO slow, and it's selectively blocked by KV4 channel toxin SNX 482. Using current clamp experiments, they found that regional differences in action potential wave forms, with a notch in phase one in the left ventricular subepicardial myocytes. In failing, left ventricular subepicardial myocytes, ITO fast was reduced, while ITO slow was increased. In addition, the notch and plateau potentials were depolarized, and action potential durations were prolonged, both statistically significantly. Slowing ITO fast inactivation results in a dramatic action potential shortening. The authors concluded that remodeling of ITO fast in failing, human left ventricular subepicardial myocytes, attenuates transmural differences in action potential wave forms. In our next paper, Ravi Vaidyanathan and associates examine the interaction between Caveolin 3 domain in the inward rectifier potassium channels. Although the IK1 current is mainly composed of Kir2.1, there are Kir2.2 and Kir2.3 heterotetromerisoforms that occur and modulate the IK1 current, but these have not been studied. Kir2.x isoforms have unique, subcellular co-localization in human cardiomyoctyes and co-immunoprecipitate with Cav3. Using induced pluripotential stem-cell-derived cardiomyocytes, the LQT9 Cav3 mutation, F97CCav3 resulted in actual potential prolongation. Based on the technique FRET, which is Fluorescent Resonance Energy Transfer, the authors calculated the distance between KR2.2 and cath ray proteins to be 6.61 nanometers. LQT9 is caused by Cav3 mutations. Prior work has shown that F97CCav3 mutation increases the late sodium current, and decreases KR2.1 current density by distinctive mechanisms. This study extends the authors' previous observations on the impact of LQT9 Cav3 mutation on Kir2.1 current, by demonstrating that mutation affects the Kir2.2 current. LQT9 causing Cav3 mutation differentially regulates current density and cell surface expression of Kir2.x homomeric and heteromeric channels. The authors show that the mutation does not affect Kir2.3 current, but the heterotetromer Kir2.2-2.3 demonstrated loss of function. Using the Li-Rudy [inaudible 00:09:45] model and myocyte mathematical model, the authors' data suggest that both loss of IK1 and increased sodium L are required for arrhythmia generation in LQT9. In our next study, Christophe Teuwen and associates use high resolution epicardial mapping electrodes, 128 or 192, with an inter-electrode distance of 2.0mm of the entire atrial surface in 164 patients. These patients were undergoing open-chest cardiac surgery. This study was designed to examine the conduction of atrial extrasystoles. The authors found that a higher degree of aberrancy was associated with a higher instance of conduction disorders. Most conduction disorders were provoked by atrial systoles emerging as epicardial breakthroughs. Atrial extrasystoles cause most conduction disorders in patients with left atrial dilatation or diabetes mellitus. In our next paper, Yuki Komatsu and associates examine 31 patients with idiopathic ventricular arryhthmias, using a two french microcatheter placed in a communicating vein between the great cardiac vein and small cardiac venous system, which passes between the aortic and pulmonary annulae, and is located in close associated with the left ventricular summit. They found that 14 patients had summit ventricular arryhthmias. The remaining 17 patients control group had ventricular arryhthmias originate from the right ventricular outflow track in the aortic cusps.  In patients with summit ventricular arryhthmias, the earliest activation during ventricular arryhthmias in the summit, preceded to cure as onset by 34 milliseconds. The summit ventricular arryhthmias exhibited inferior axes, negative polarity in lead one, deeper Q wave in AVL than AVR, nonspecific bundle branch morphology with an RS ratio in lead V1 of 0.67, distinguishing them from arryhthmias originating from the right ventricular outflow track or right ventricular cusp. Overall, ablation success was achieved in 10, or 71% of patients with summit ventricular arryhthmias, and 88% in the control group, P = 0.24. In our final paper, Deepak Padmanabhan and associates examine differences in mortality in patients with non-MRI conditional CID undergoing brain MRI compared to controls. Patients with CIDs undergoing brain MRI were compared with three control groups matched for age, sex, imaging year, and type of CID. These groups included 1) no CID and brain MRI, 2) CID in brain-computed CT, and 3) no CID in brain CT. They estimated all cause mortality at five years for CID MRI group, was not significantly different from patients who underwent CT, with or without a device. There was a significant increase in the mortality between CIED versus no CID MRI groups, hazard ratio 1.46 with a P value of 0.04. That's it for this month, but keep listening. Saraj 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 Saraj. Saraj Kapa:                          Thank you Paul, and welcome back to On the Beats where this month we'll be focusing on articles that are particularly hard-hitting, published across the literature in December of 2017. It's my pleasure to introduce 20 different articles that seem to have either particular interest or might change the field in the future. First, within the area of atrial fibrillation, we'll focus within the area of anticoagulation and stroke prevention. In the Journal of the American College of Cardiology, Vivek Reddy et al published on the five-year outcomes after left atrial appendage closure, from the Prevail and Protect AF trials. They included a total of 1,114 patients, with a total of 4,343 patient years of follow-up, randomized two to one to closure versus Warfarin. While ischemic stroke and systemic embolism of [inaudible 00:14:32] were numerically higher with closure, this did not reach statistical significance in terms of hemorrhagic stroke, unexplained death, and post-procedure bleeding favor left atrial appendage closure. These findings further support a role for left atrial appendage closure in the specific groups of patients enrolled in the Protect and Prevail Studies. Of course, we always need to understand, that extrapolation to patients who may not have met inclusion criteria will be difficult. In particular, given both trials had their own fundamental limitations in the Prevail study. There was a relatively low rate of [inaudible 00:15:09] in the Warfarin arm. And in turn, there was a relatively high complication rate in Protect AF with left atrial appendage closure. Part of the differences might be due to the fact that, with more experience, complication rates might decrease. Furthermore, a comparison with more novel agents, such as the new oral anticoagulants, remains to be seen. Next, within the realm of cardiac mapping and ablation for atrial fibrillation, we review an article by Vlachos et al published in the Journal of Cardiovascular Electrophysiology entitled Low-Voltage Areas Detected by High-Density Electroanatomical Mapping for Recurrence of Ablation after a Paroxysmal Atrial Fibrillation. They presented the results from a series of 80 patients undergoing ablation for paroxysmal atrial fibrillation, performing high-density voltage mapping to characterize the total area involved by low voltage. They demonstrated, when low voltage areas, defined as less than 0.4 millivolts, were seen in greater than 10% of the left atrial surface area, this served as an independent predictor of atrial fibrillation recurrence. These data support prior research, including that of MRIs, suggesting the characterization of the atrial substrate may correlate with likelihood of ablation success. Identifying methods however, to accurately and reproduce will identify these patients with more atrial substrate prior to ablation, remains to be seen. The importance of this, however, is our ability to better counsel patients on the likelihood of treatment success. Next within the realm of atrial fibrillation, we review elements of risk stratification managements. First, in the December issue of the Journal of American College of Cardiology, Takimoto et al published on how Eplerenone may reduce atrial fibrillation burden without preventing atrial electrical remodeling. In a randomized controlled ovine atrial tachy pacing model of atrial fibrillation. The authors provided daily, oral Eplerenone and compared this with a placebo. They showed that Eplerenone significantly reduced the rate of left atrial dilatation, with less smooth muscle actin protein, atrial fibril [inaudible 00:17:17]. Furthermore, Eplerenone further prolonged the time to persist in atrial fibrillation in 26% of animals. However, interestingly, Eplerenone did not prevent AF-induced electrical remodeling.  These data suggest that Eplerenone, or other medications that can be used to prevent or reverse structural remodeling, may offer an upstream therapy to reduce atrial fibrillation burden, and decrease likely the persistent atrial fibrillation. Giving the ever-growing population of patients suffering from atrial fibrillation, identifying upstream approaches to prevent it will be critical. Of course, these need to be taken with due consideration, however. Specifically, the model used here, namely that of an atrial tachy pacing model, might not be applicable to all human atrial fibrillation. Thus, whether or not such therapies actually offer benefit in clinical models, is as of yet unclear. Finally, from the realm of atrial fibrillation, we review the article by Rowin et al published in circulation entitled Clinical Profile of Consequences of Atrial Fibrillation Hypertrophic Cardiomyopathy. In patients presenting with hypertrophic cardiomyopathy, atrial fibrillation is known to be a significant co-morbidity. However, the implications of atrial fibrillation in terms of worsening of heart failure status, or long-term morbidity mortality are less clear. Rowin et al reviewed the natural history of atrial fibrillation amongst 1,558 patients, prospectively followed at a single center. Nearly 20% of the population developed atrial fibrillation with the majority having symptomatic paroxysmal atrial fibrillation. However, atrial fibrillation was not associated with any increase in cardiovascular mortality or worsening of heart failure status. Furthermore, mortality that was directly related to atrial fibrillation was nearly exclusively related to thrombolic stroke. Anticoagulation [inaudible 00:19:13] reduced this risk. The traditional scoring systems fared poorly in assessing the stroke risk of this population. About 121 patients underwent invasive rhythm control approaches, including 72 patients undergoing maze and 49 catheter ablation. The success rate of maze was significantly greater at around 75%. These data are important when counseling hypertrophic cardiomyopathy patients presenting with new-onset atrial fibrillation. While it is clear that paroxysmal atrial fibrillation has a significant impact on symptoms and quality of life, it does not cause worsened, overall, long-term outcomes. However, it does highlight the importance of anticoagulation in this population, nearly irrespective of the underlying risk score. In terms of rhythm control options, it appears that rhythm control options can be successful in these patients. Finding that catheter ablation is associated with a 40 to 50% success rate is in keeping with prior published data. Thus, consideration of when a patient needs to be referred to maze, needs to be considered in the clinical inpatient context. Changing gears, we will next review articles within the realm of ICDs, pacemakers, and CRT. In the New England Journal of Medicine this past month, Nazarian et al published on their experience regarding the safety of magnetic resonance imaging in patients with cardiac devices. They performed a prospective non-randomized study of the safety of, specifically, 1.5 tesla-strength MRI scans on legacy. In other words, not MRI conditionally-safe pacemakers and defibrillators. A total of 2,103 scans were done among 1,580 patients. They demonstrated no long term clinically significant adverse events. Nine patients did experience a reset to a backup mode, though eight of which were transients. The most common change seen acutely was a decrease in PVA amplitude in one percent of patients, and in a long term follow-up, 4% of patients experiencing a decrease in PVA amplitude, increase in atrial catheter sheer threshold, or increase in right or left ventricular capture threshold. However, none of these events were considered clinically significant. Furthermore, there was not a good [inaudible 00:21:23] group to know if this long term change in amplitudes or thresholds might have been seen in patients who had devices that were not exposed to MRI. These findings are complimentary to multiple, prior, published reports, indicating the safety of performing MRIs under clinical protocol in legacy pacemakers and defibrillators. It calls into question whether MRI conditional devices truly offer an additional safety factor furthermore, over legacy devices. Next we review an article by Lakkireddy et al published in Heart Rhythm entitled A Worldwide Experience, the Management of Battery Failures and Chronic Device Retrieval of the Nanostim Leadless Pacemaker. Lakkireddy et al reported their large multi-center experience on the overall risk of battery failure. Amongst 1,423 implanted devices there were 34 battery failures occurring, on the average, three years after implants. Furthermore, about 73 patients underwent attempted device retrieval, and this was successful in 90%, with the seven failures of retrieval being due to either inaccessibility of the docking button, or dislodgement of the docking button in one patient, in whom it embolized to the pulmonary artery. An additional 115 patients interestingly received an additional pacemaker after release of the device advisory. These data suggest that there may be as high as an overall 2% risk of battery failure with the Nanostim device, even late after implants. This highlights the need for close follow-up, even if the battery appears relatively stable up to two year after implants. Furthermore, almost 10% of devices cannot be successfully retrieved. However, in those patients, even with re-implantation of a separate device, there was no device-device interaction seen. Further innovation will be needed to optimize device longevity, and close follow-up of all patients undergoing implantation will be critical to understand the overall long term efficacy and safety when compared to other traditional devices. Finally, within the realm of device care, we focus on an article by Kiehl et al, again published in Heart Rhythm this past month entitled Incidence and Predictors of Late Atrial Ventricular Conduction Recovery Among Patients Requiring Permanent Pacemaker for complete heart block after cardiac surgery. They reviewed the likelihood of recovery of conduction in their retrospective cohort of 301 patients. Interestingly, 12% of patients had recovery of AV conduction on average six months after surgery. Those who did not recover tended to more likely have preoperative conduction abnormalities. Saraj Kapa:                          Findings that suggested a higher likelihood of long term conduction recovery included female sex and the existence of transient periods of AV conduction postoperatively. These data highlight that recovery of AV conduction is possible in a significant number of patients undergoing cardiac surgery. However, being able to predict long term recovery may assist in device selection, to avoid more costly device implantations that may not be needed over chronic follow-up. Prospective studies amongst larger numbers of patients are needed to better understand mechanisms of block, mechanisms of recovery, an optimal device in patient selection. Changing focus, we will next review two articles within the realm of supraventricular tachycardias. First we read an article by Han et al published in JACC Clinical Electrophysiology, entitled Clinical Features in Sites of Ablation for Patients With Incessant Supraventricular Tachycardia From Concealed Nodofascicular and Nodoventricular Tachycardias. Han and group describe three cases of concealed nodovascicular, nodoventricular re-entrant tachycardias, and focus on the different mechanisms of proving their participation in tachycardia. In all cases, atrial ventricular re-entering tachycardia was excluded. Successful ablation for these tachycardias occurred either at the slow pathway region, the right bundle branch, or the proximal coronary sinus. This is the first described case of incessant, concealed tachycardias related to these pathways. The importance of this article highlights an understanding the mechanisms proving the contribution to tachycardia, and the importance of recognition when performing electrophysiology studies, and being unable to reveal traditional mechanisms, which exist in most patients, such as atrial tachycardia, AVNRT or AVRT. Next we review an article by Guo et al published in Europace entitled Mapping and Ablation of Anteroseptal Atrial Tachycardia in Patients With Congenitally Corrected Transposition of the Great Arteries: Implications of Pulmonary Sinus Cusps. They reviewed three separate cases of anteroseptal atrial tachycardias in the setting of congenitally corrected transposition. They demonstrated that in these cases, there was successful ablation performed with the pulmonary sinus cusps. The result is successful and durable suppression. The reason this article is important lies in the fact that it's critical to understand both cardiac anatomy and cardiac nomenclature. The pulmonary valve in CCTJ is affectively the systemic ventricular arterial valve, given that the right ventricle is the systemic ventricle. Thus, mapping in this region of CCTJ abides the same principles as mapping the aortic valve in structurally normal hearts for similar tachycardias. However, understanding the nomenclature and that despite the variant anatomy, the utility of similar approaches to mapping of the systemic outflow are important when matching these complex, congenital anatomy or arrhythmia patients. Changing gears yet again, we review an article within the realm of sudden death and cardiac arrest. Baudhuin et al published in Circulation and Genetics entitled Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death. Baudhuin et al reviewed the utility of formal and fixed paraffin-embedded tissue, which is routinely obtained in an autopsy, to perform post-mortem, genetic testing. One of the main limitations to advising family members who have had prior family history of sudden death in closely related relatives, is that blood is often not available to perform DNA screening late after death. DNA however is often degraded in the tissues that are commonly available at autopsy, namely the formal and fixed paraffin-embedded tissues. The authors sought to evaluate if your next generation techniques could make these types of tissue adequate for diagnosis. They demonstrated amongst 19 samples, that performance characteristics were similar between whole blood and these tissue samples, which could be as old as 15 years. It can be critical to identify disease-causing mutations in family members, as individuals who might not yet be affected, but at risk, need to know about that overall risk. Given that decision to sequence might also not be universally applied at all centers, or in all situations, oftentimes these paraffin-embedded tissues might be the only available option, sometimes over a decade after death. This represents the first report of using next-generation sequencing approaches to successfully and accurately sequence for specific mutations using paraffin-embedded tissue. This may offer additional options to help family members achieve diagnoses for sudden death-inducing conditions. Within the realm of cellular electrophysiology, we review an article by Lang et al published in Circulation Research entitled Calcium-Dependent Arrhythmogenic Foci Created by Weakly Coupled Myocytes in the Failing Heart. Lang et al reviewed the effect of cell-cell coupling on the likelihood of triggered arryhthmias. In a [inaudible 00:28:45] model, they demonstrated the myocytes that are poorly synchronized with adjacent myocytes were more prone to triggered activity due to abnormal calcium handling when compared to myocytes with normal connection to adjacent cells. Thus, adequate coupling leads to voltage clamping during calcium waves, thus preventing triggering arrhythmias. While poorly coupled myocytes aren't able to to this due to a weakened currency, making them more prone arrhythmogenesis. These data highlight another critical cellular basis for arrhythmogenesis. In heart failure, while the focus for clinical management is typically areas of scar, there's clearly a role at the cellular level where cell-cell coupling abnormalities can lead to dynamic changes that can increase tendencies to arrhythmogenesis. The role in understanding the varying, arrhythmogenic risk based on varying factors, is important, and might have importance in the future advances in mapping technologies. Changing gears, we review an article published in the Journal of the American College of Cardiology by Mazzanti et al within the realm of genetic channelopathies entitled Hydroxyquinoline Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. They reviewed a cohort of 17 patients and demonstrated that hydroxyquinoline resulted in a reduction of arrhythmic events from 40% to 0% of patients. QTc prolongation was seen in all patients. These data clearly demonstrate that hydroxyquinoline plays a role in lowering the incidence of arrhythmic events in patients suffering from short QT syndrome. However, it's important to note that in many markets, quinoline has been difficult to access. In the specific case of QT syndrome thus, there's clearly a role for hydroxyquinoline. However, it also must be noted, the comparative efficacy with more commonly available drugs still needs to be evaluated. This past month has been of particular interest in the realm of ventricular arrhythmias, with multiple, potentially ground-breaking articles. One of the well-recited articles published this past month already is by Cuculich et al entitled Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia published in the New England Journal of Medicine. Cuculich et al reported the first in-human data on the use of stereotactic body radiation therapy to perform noninvasive ablation of ventricular arryhthmias. Using a combination of noninvasive electrocardiographic imaging curing ventricular tachycardia, and stereotactic radiation, patients were treated with a single fraction of 25 [inaudible 00:31:15] while awake. A total of five patients were included with a mean ablation time of only 14 minutes. During the three months prior to treatment, there was a total of 6,577 VT episodes seen, and during a six week post-ablation period, considered a blanking period, there were 680 episodes. After this blanking episodes, there were only four episodes of VT seen over the ensuing 46 patient months. This study is important because it reflects the first in-human proof of concept that noninvasive ablation using radiation therapy traditionally as for treatment of solid tumors, may be affective in targeting cardiac tissue. Furthermore, modern techniques such as noninvasive electrocardiographic imaging might allow for a fully noninvasive experience for the patients. This is a vast advance seen within the realm of cardiac electrophysiology. In the early days, all we could do was map invasively and then have to go to much more invasive, open-heart surgery to treat arryhthmogenic substrates. Since the advent of catheter and radiofrequency ablation, surgical ablation is relatively fallen by the wayside, to a less invasive approaches. A completely noninvasive approach to successfully targeting tissue is potentially ground-breaking. However, there are several limitations in this study that can only be ascertained by reading the actual article. When we actually review the patients included, the long term follow-up was limited to only four patients, as one patient actually died within the blanking period, and in fact, this patient suffered from the largest burden overall of VT. Furthermore, amongst the remaining four patients, one required a redo ablation within the blanking period, and one had to be restarted on amioderone after the blanking period was over. Thus further data is really needed to clarify efficacy, given the overall success rate appears to be less than 50% on a per patient basis. Though on an overall episode basis, there was significant reduction. The exact type of radiation to be used also needs to be considered, within the realm of solid oncology. Stereotactic radiation is considered an older modality, with proton beam, and more recently, carbon beams offer more directed therapy. Thus, a lot more data is required to identify the promise of radiation therapy. Though again, this is a significant advance. Next, within the realm of invasive electrophysiology, we review an article by Turagam et al published in the JACC Clinical Electrophysiology entitled Hemodynamic Support in Ventricular Tachycardia Ablation: An International VT Ablation Center Collaborative Group Study. The utility of hemodynamic support during VT ablation is relatively unclear. Studies have been variable and limited. This group included 1,655 patients who underwent 105 VT ablations using hemodynamic support with a percutaneous ventricular assist device. Those undergoing support overall tend to be sicker, including lower ejection fractions and [inaudible 00:34:07] classes, and more VT events, including ICD shocks and VT storm. Hemodynamic support use interestingly, was an independent predictor of mortality with a hazard ratio of 5, though there was no significant difference in VT recurrence rates irrespective of the subgroup considered. These data indicate that, while patients are receiving hemodynamic support were overall sicker, there was no clear incremental benefit in use of hemodynamic support in terms of long term outcomes. In the area of substrate ablation, whether use of hemodynamic support to facilitate mapping during VT, actually alters outcomes remains to be seen. This study highlights the potential importance of randomized clinical approaches to better evaluate whether hemodynamic support truly alters the long term outcomes of the VT ablation. Next, we review an article by Munoz et al that focuses more on prediction of those patients who might be at risk for ventricular arrhythmias, again published in the last edition of JACC Clinical Electrophysiology and entitled Prolonged Ventricular Conduction and Repolarization During Right Ventricular Stimulation Predicts Ventricular Arrhythmias and Death in Patients With Cardiomyopathy. Munoz et al reviewed the relationship between paced QRS and pace Qtc and long term risk. A total of 501 patients with mean ejection fractions of 33% were included. Longer paced ventricular QRS and Qtc was associated with a higher risk of ventricular arrhythmia, and all caused death or arrhythmia, irrespective or ejection fraction. A paced QRS duration of 190 milliseconds was associated with 3.6 fault higher risk of arrhythmia, and a 2.1 fault higher risk of death or arrhythmia. These data suggest that findings during [inaudible 00:35:47] pacing and otherwise normal rhythm, including paced QRS and QTc may independently result in elevation of overall risk of ventricular arrhythmia and death. Physiologically these data make sense. In light of the fact that longer cure restorations are probably related to a greater degree of myopathy. While these data offer a prognostic indication, whether they alter outcomes or decision making regarding ICM implantation, remains to be seen. Next, also published in JACC Clinical Electrophysiology, Vandersickel et al reviewed a more cellular basis for toursades in an article entitled Short-Lasting Episodes of Toursades de Pointes in the Chronic Atrial Ventricular Model Have Focal Mechanism While Longer-Lasting Episodes are Maintained by Reentry. Vandersickel et al reviewed the mechanisms underlying toursades, and demonstrated that both focal and reentry mechanisms may exist. In five canines they used broadly distributed neuro electrodes to simultaneously map across the heart. They demonstrated that initiation and termination was always focal, but longer and non-terminal episodes always had reentry mechanisms. These data suggest that the mechanisms underlying toursades actually reflect a spectrum of potentially dynamic, electrophysiologic phenomenon the heart, including both focal and reentry activity. Understanding these mechanisms, and the fact that focal mechanisms almost universally underlie initiation may bring into consideration the optimal treatments whether in the form of pacing and defibrillation techniques or medication techniques for toursades. Finally, in the realm of ventricular arrhythmia, we review an article published in the last month's edition of Heart Rhythm by Penela et al entitled Clinical Recognition of Pure Premature Ventricular Complex-Induced Cardiomyopathy at Presentation. As we know, it's sometimes difficult to recognize patients when they present with frequent PVCs and a depressed injection fraction in terms of, whose injection fractions are purely caused by the presence of PVCs, and whose PVCs are only exacerbated by the presence of an underlying myopathy. The group included 155 patients and excluded all patients who did not normalize their elevated ejection fraction, or who had previously diagnosed structural heart disease, leaving a total cohort under consideration, of 81 patients. About 50% were diagnosed as having a PVC-induced cardiomyopathy on the basis of normalization of elevated function after PVC suppression. While the remainder was considered to have PVC exacerbated cardiomyopathy on the basis that things did not entirely resolve, and thus had an independent mechanism for nonischemic myopathy. Characteristics that suggested patients with a lower likelihood of EF normalization included those with longer intrinsic QRSs, above 130 milliseconds, a lower PVC burden of baseline, considered less than 17%, and larger [inaudible 00:38:33] greater than 6.3 cm. PVCs as a cause of [inaudible 00:38:35] are obviously a well-recognized treatable cause of myopathy, however again, it might be difficult to differentiate. Those patients whose PVCs are a result of the underlying myopathy versus those whose PVCs are the cause, and for whom ablation or suppression may reverse the myopathic process. The work of Penela et at offers an initial attempt at helping differentiate these processes, however validation of larger cohort is necessary. Next we review an article within the realm of syncopy entitled Prohormones in the Early Diagnosis of Cardiac Syncopy by Badertscher et al published in the Journal of the American Heart Association this month. They review the utility of circulating prohormones [inaudible 00:39:14] autonomic dysfunction or neurohormonal abnormalities, to differentiate cardiac from non-cardiac causes of syncopy in the emergency departments. They measured four novel prohormones in a multi-center study. In the emergency departments there is a specific protocol used to determine the perceived likelihood of the cause of syncopy to be cardiac versus non-cardiac. In addition to this, the prohormones are drawn. After this, everyone's final diagnosis was reached. Two independent cardiologists reviewed the cases to determine if it was a truly cardiac or non-cardiac cause of syncopy. Among 689 patients included, 125 overall were adjudicated as cardiac syncopy. Measure of the specific marker MR-proANP in combination with emergency department suspicion of syncopy, performed better than suspicion alone, to differentiate cardiac causes of syncopy. A combination of a circulating MR-proANP, less than 77, picomoles per liter, an [inaudible 00:40:17] probability of cardiac syncopy could be less than 20%, had a very high sensitivity negative predictive value of 99%. The significant resources are often used to manage patients with syncopy presenting to the emergency departments, and it's often extremely difficult at this stage to differentiate cardiac from non-cardiac causes of syncopy. And the amount of evaluation that can be done in the emergency department is often limited. Cardiac caused of syncopy are not good to miss, however, since these can include ventricular arrhythmias, and transient AV block, that might result in death as well. As is well-recognized, emergency department evaluation in clinical [inaudible 00:40:49] are limited in terms of their utility. This raises the utility of objective measures to help differentiates. These data suggest that circulating prohormones [inaudible 00:40:59] your hormonal function drawn during your emergency department evaluation, may be a useful adjunct to differentiate cardiac from non-cardiac syncopy. Whether they can be used to prospectively differentiate those patients requiring inpatient admission or now, however, remains to be seen. The last two articles we'll choose to focus on will fall under the realm of broader, other EP concepts. The first article we will review is by Varghese et al published in Cardiovascular Research entitled Low-Energy Defibrillation With Nanosecond Electric Shocks. Varghese et al reviewed the potential of low-energy nanosecond duration shocks for defibrillation in rapid hearts. In induced fibrillation examples, the repeated defibrillated nanosecond impulses as low as three kilovolts demonstrated effective defibrillation. The energy required is significantly lower than from monophasic shocks and longer pulse durations. Furthermore, there was no detectable evidence of electroporation, namely cardiac or so injury after defibrillation. Using nanosecond impulses, it may be feasible to defibrillate the heart with significantly lower energies. The implications for patients experiencing defibrillation, for example pain, is unclear without in-human studies. However, the ability to use lower energies could have implications in battery life. Further [inaudible 00:42:11] studies will be critical to study ambulatory efficacy as this research is performed in [inaudible 00:42:19] hearts. Finally, we review an article published in Circulation entitled Mortality in Supravascular Events After Heart Rhythm Disorder Management Procedures by Lee et al. Amongst three centers, a retrospective cohort study regarding the mortality and risk of supravascular events, was performed. They included a variety of heart rhythm [inaudible 00:42:40] procedures, including defibrillation threshold testing, lead extraction, device implant, and invasive electrophysiology studies and ablation procedures. Amongst 48,913 patients, 62,065 procedures were performed and an overall mortality of .36% was seen. Supravascular [inaudible 00:42:58] was lower at .12%. Interestingly, and expectedly, the highest risk was seen with lead extraction patients, with an overall mortality risk of 1.9%. Less than half of the deaths seen, however, were directly attributable to the procedure itself. The most common cause of procedural death was cardiac tamponade, largely seen amongst device implant patients. This is critical, as the number of ablation and other invasive electrophysiology procedures performed, is increasing. These data provide a large, contemporary experience regarding the overall risk attributable to a variety of heart rhythm disorder procedures. Interestingly, half of the procedure related deaths were associated with device implantation procedures. With the predominant cause being tamponade, highlighting the importance of early recognition of this treatable complication. Tamponade may not always be considered as a major issue after device implantation, however these data clearly suggest that it is. In addition, extraction, as expected, carried the highest incident of both supravascular events and mortality. Though, this is likely related to the higher rate of core morbidity in this population, including active infection. In summary, this month, we have reviewed 20 articles in various areas of electrophysiology published across the literature. Particularly high impact articles range from those reviewing experience regarding left atrial appendage closure and the efficacy of this, to the utility of using atrial fibrillation to predict risk and long term morbidity and mortality in hypertrophic cardiomyopathy, to further evidence regarding the safety of magnetic resonance imaging in legacy pacemakers and defibrillators, and novel considerations regarding supraventricular tachycardias and there diagnosis and management, especially invasively. Other potential groundbreaking articles included evidence that we can successfully use formal and fixed paraffin-embedded tissue that can be as old as 15 years, to successfully identify genetic mutations that might be responsible for sudden death. And evidence that using novel techniques, we might be able to perform completely noninvasive therapies for arrhythmias by using radiation therapies. However questions were also raised such as regarding the role of hemodynamic support for VT ablation. How to better differentiate those patients who will have recovery of AV conduction from those who won't, as they meet class I indications post cardiac surgery? And whether other factors such as right ventricular pacing during [inaudible 00:45:28] study might further differentiate patients at risk for ventricular arrhythmias in spite of a low ejection fractions. Many of the papers had to deal with tranlational work that still remains to be proven in terms of value at a clinical level, such as demonstrating mechanisms underlying trousades de pointes. Or the potential value of low-energy defibrillation with nanosecond electric shocks. Clinical protocols involving the use of prohormones in the early diagnosis of cardiac syncopy. How to differentiate PVC induced from other causes of myopathy, and how to manage, in the long term, these devices. Also, likely requires further study. Finally, covering all areas of electrophysiology, we reviewed one large article focusing on mortality in supravascular events after heart rhythm management disorder procedures at large. This article highlights the importance of considering institutional experience and reporting it to use as a benchmark to help better optimize our counseling of patients, as well as our procedures and protocols. I appreciate everyone's attention to these key and hard-hitting articles that we just focused on from this past month of cardiac electrophysiology across the literature. Thanks for listening. Now, back to Paul. Dr. Paul Wong:                  Thanks Seraj. 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 advance. 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 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.    

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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.