Podcasts about epicardial

Today, Dr. O'Mara is the only physician in the world specializing in health and performance optimization. He works with individuals and corporations interested in the biological optimization of humans through innovation and safe, natural lifestyle strategies shown to be more effective than medications. He especially enjoys working with exceptionally motivated individuals such as business executives, professional performers, and athletes whose livelihoods are predicated upon performance. In 2016, he was awarded a $1.2 million grant from the National Science Foundation for research on reversing chronic disease using innovative biomarkers such as visceral and pericardial fat. Instagram: https://www.instagram.com/drseanomara Twitter: https://x.com/DrSeanOMara YouTube: https://youtube.com/@drseanomara Other: https://www.growingbetternotolder.com/links Website: https://drseanomara.com/ Timestamps: 00:00 Trailer. 00:53 Introduction. 04:21 Visceral fat as a better marker. 08:08 Abdominal diameter indicates visceral fat. 12:03 Adiponectin benefits health but hides six-packs. 15:36 Facial changes and fat. 17:53 Facial indicators of health. 22:15 Visceral fat reduction improved health outcomes. 23:08 Epicardial and visceral fat increase risks of AFib. 28:18 Visceral fat is bad. 29:03 Grass-fed beef has higher omega-3 content. 33:28 Sprinting reduces visceral fat. 38:05 Sprinting safety. 43:42 Hills improve sprinting technique and safety. 46:29 Intense exercise and stress elimination reduce fat. 48:36 Heart fat reduces fastest, then visceral fat. 51:47 Where to find Sean. See open positions at Revero: https://jobs.lever.co/Revero/ Join Carnivore Diet for a free 30 day trial: https://carnivore.diet/join/ Carnivore Shirts: https://merch.carnivore.diet Subscribe to our Newsletter: https://carnivore.diet/subscribe/ . ‪#revero #shawnbaker #Carnivorediet #MeatHeals #HealthCreation   #humanfood #AnimalBased #ZeroCarb #DietCoach  #FatAdapted #Carnivore #sugarfree  ‪

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on AI prediction of cardiovascular events using opportunistic epicardial adipose tissue assessments from computed tomography calcium score.

Audio Commentary by Dr. Valentin Fuster, Emeritus Editor in Chief

Commentary by Dr. Candice Silversides

Host Dr. Jonathan Revels summarizes the RadioGraphics article titled “Epicardial Space: Comprehensive Anatomy and Spectrum of Disease”. Epicardial Space: Comprehensive Anatomy and Spectrum of Disease. Roset-Altadill et al. RadioGraphics 2024; 44(4):e230160.

Commentary by Dr. Candice Silversides and Dr. Valentin Fuster

In this month's edition, Pooja speaks with Mike Gillham and Tom Barr regarding their article titled 'Temporary Epicardial Pacing After Cardiac Surgery.' They delve into the importance and procedural aspects of performing pacing checks both during surgery and in the postoperative phase. Additionally, they explore the intricacies of caring for patients within this particular group.

Commentary by Dr. Valentin Fuster

CardioNerds Amit Goyal, Dr. Colin Blumenthal, Dr. Kelly Arps and Dr. Justice Oranefo discuss mechanical stroke prevention in atrial fibrillation with Dr. Christopher Ellis, cardiac electrophysiology lab director and director of the left atrial appendage closure program at Vanderbilt University. There has been a significant increase in the number of patients undergoing left atrial appendage occlusion (LAAO). This trend is expected to continue with current and upcoming clinical data on this topic. In this episode we dive into the rationale behind LAAO and explore several historical facts. We then proceed to the current state of practice including currently available options, appropriate indications, post op care, and potential complications. Notes were drafted by Dr. Justice Oranefo. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: Dr. Ellis discloses grant or research support from Boston Scientific, Abbott-St Jude, advisor for Atricure and Medtronic. CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation Surgical or catheter based left atrial appendage occlusion results in mechanical exclusion of the left atrial appendage, which is the most common source of thrombus leading to embolic events in patients with non-rheumatic atrial fibrillation. Surgical LAAO should be considered in patients with atrial fibrillation and CHA2DS2VASC score ≥ 2 undergoing cardiac surgery for other indications. Endocardial LAAO devices such as WATCHMAN FLX and AMULET are approved for stroke prevention in patients with atrial fibrillation with a CHA2DS2VASC score ≥ 2 and have an appropriate reason to seek a non-drug alternative to anticoagulation therapy. Appropriate patient selection and post-operative anticoagulation and imaging strategy are crucial for prevention and management of complications related to LAAO. Notes - Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation What are the types of LAAO device? Left atrial appendage occlusion devices can be divided into epicardial closure and endocardial closure. Epicardial techniques/devices include surgical ligation, Atriclip, and Lariat. These techniques require pericardial access (either by open thoracotomy or thoracoscopic access). The goals are complete exclusion and ischemic necrosis of the LAA. LARIAT device Atriclip device Endocardial techniques include WATCHMAN FLX and AMULET devices. These techniques require the use of nitinol-based devices which are delivered into the LAA via a transeptal approach. These devices become endothelialized over time resulting in occlusion of the LAA. AMULET device WATCHMAN FLX Who is the ideal candidate for surgical LAAO? Several studies have evaluated the efficacy of surgical LAA occlusion. The most prominent being the LAOS III trial which randomized 4770 patients with atrial fibrillation and CHA2DS2VASC ≥ 2 undergoing cardiac surgery for other reasons to surgical LAAO vs no LAAO (3,4). The primary outcome of ischemic stroke or systemic embolization occurred in 4.8% of patients in the LAAO group vs 7% of patients in control group over an average ...

Dr. Thomas Michael Tadros returns to the podcast to discuss the DECAAF II Randomized Clinical Trial. As a Board-certified Cardiologist and EP, Dr. Tadros' gives us the pros and cons and takeaways from this study, that advances AFib knowledge within our specialty. The study, “Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial” was authored by Marrouche, Wazni, McGann et al and just released in June 2022 by JAMA. Key points from the paper: ● Question: Among patients with persistent atrial fibrillation (AF), does the addition of magnetic resonance imaging (MRI)-guided fibrosis ablation to conventional catheter ablation affect atrial arrhythmia recurrence?● Findings: In this randomized clinical trial that included 843 patients with persistent AF, there was no significant difference in atrial arrhythmia recurrence in the MRI-guided fibrosis ablation group compared with the pulmonary vein isolation only group (hazard ratio, 0.95).● Meaning: Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent atrial fibrillation. All Things Afib is hosted by me, Dr. Armin Kiankhooy. As a board-certified cardiothoracic surgeon, my focus is on advanced treatments for heart and lung failure and minimally-invasive surgical treatments for atrial fibrillation such as the Hybrid Maze procedure. You can find me on staff at Adventist Health Heart and Vascular Institute in St. Helena California. Discussion points: ● Persistent vs. Paroxysmal Afib and background on the DECAAF I study● Using MRIs to identify fibrosis prior to ablation● Follow-up testing showed no differences - 43-46% of patients had a recurrence of AFib● Patients were all approximately one year out from their diagnosis● Even in patients with only 7 days of Afib, there was significant fibrosis – due to history of hypertension?● Interstitial vs. replacement fibrosis● Stroke incidence and mortality after the procedure● Epicardial procedures - does this study impact?● Where do we go with the data from this study? Does it impact practice?● Scalability of this data/study/impact● Overall these studies continue to be extremely relevant Resources: DECAAF II Study in JAMA Dr. Thomas Michael Tadros at Brigham and Women's Dr. Kiankhooy LinkedIn All Things AFib Website All Things AFib Twitter All Things AFib YouTube Channel

Commentary by Dr. Emile Daoud

Commentary by Dr. Valentin Fuster

Commentary by Dr. Colleen Clancy

First join author Marc Dweck and Associate Editor Victoria Delgado as they discuss the article "Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial." Then, join authors Torbjørn Omland and Geeta Gulati as they discuss the article "Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol." 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: I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center, VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Hooray, it's another double feature week! And guess what, these two papers are two randomized control trials. One looking at progression of aortic stenosis and the other, looking at a prevention of cardiac dysfunction following adjuvant breast cancer therapies. Dr. Carolyn Lam: So, very interesting two papers coming right up. But Greg, why don't you start by highlighting some of your favorite papers from today's issue. Dr. Greg Hundley: You bet Carolyn. Dr. Greg Hundley: So my first study was conducted by Dr. Gabriela Trifan and colleagues from University of Illinois who performed a meta analysis of major studies that compare the efficacy and safety of dual anti-platelet therapy versus monotherapy for secondary prevention of recurrent stroke or transient ischemic attack in those previously experiencing minor non cardioembolic stroke. And their primary outcomes were stroke and the composite of stroke, TIA, acute coronary syndrome and death of all cause. And the safety outcome was major hemorrhage. Dr. Carolyn Lam: Oh, okay. Very important study. What did they find? Dr. Greg Hundley: Right Carolyn. So the analysis included 27,358 patients. And compared with monotherapy, dual anti-platelet therapy reduced the risk of recurrent stroke and the composite outcome, but increased the risk of major bleeding. And in subgroup analysis at less than or equal to 30 days, dual anti-platelet therapy increased the risk of hemorrhage relative to monotherapy. In sensitivity analyses, the risk for hemorrhage with less than or equal to 30 days of dual anti-platelet therapy, after excluding the combination of aspirin plus Ticagrelor, was comparable to monotherapy. However, the risk of stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remained decreased compared to monotherapy. Dr. Greg Hundley: And so Carolyn, the take-home message from this paper is that dual anti-platelet therapy decreases the risk of recurrent stroke and composite events compared with monotherapy. But, dual anti-platelet therapy increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus Ticagrelor. Dr. Carolyn Lam: Ah, thanks for that last take home message. Thank you. Dr. Carolyn Lam: Well, the paper I'm going to tell you about is the first to examine the role of epicardial fat derived extracellular vesicles in the pathogenesis of atrial fibrillation. And this comes from Dr. Leor from Sheba Medical Center, Tel Aviv University in Israel and his colleagues who collected epicardial fat specimens from patients with and without atrial fibrillation during elective heart surgery. Dr. Carolyn Lam: Epicardial fat samples were grown as organ cultures and the culture medium was collected every two days. And the authors then isolated and purify these epicardial fat extracellular vesicles from the culture medium. Dr. Carolyn Lam: They found that epicardial fat extracellular vesicles of patients with atrial fibrillation had unique pro-inflammatory, profibrotic and proarrhythmic properties. Epicardial fat extracellular vesicles could in fact induce cellular, molecular and electrophysiological remodeling that could result in atrial fibrosis, myopathy and the development of atrial fibrillation. Dr. Greg Hundley: Wow Carolyn, so what are the clinical implications of epicardial fat extracellular vesicles? Dr. Carolyn Lam: Hmm, good question. Well, understanding their role in the pathogenesis of atrial fibrillation may for one lead to the discovery of new diagnostic markers or new targets for the prevention and treatment of atrial fibrillation. And that combined pro-inflammatory profibrotic and proarrhythmic effects of these epicardial fat and extracellular vesicles may in fact be relevant to the pathogenesis of other cardiovascular diseases associated with obesity and abnormal adipose tissue deposition. Dr. Greg Hundley: Very nice Carolyn. Dr. Greg Hundley: My next paper comes again to us from the world of preclinical science and these authors led by Dr. Masanori Aikawa from Harvard Medical School applied a systems approach in mouse experiments to discovering therapeutic targets for vein graft failure. They use global proteomics and high dimensional clustering on multiple vein graft tissues to identify potential pathogenic mechanisms. And experiments were conducted in both in vivo mouse models and in vitro human macrophages. Dr. Carolyn Lam: Oh wow. So what did they find? Dr. Greg Hundley: So Carolyn, peroxisomes proliferator activated receptors or PPAR alpha agonism by pemafibrate retarded the development and inflammation of vein graft lesions in mice, while gene silencing worsened plaque formation. Pemafibrate also suppressed arteriovenous fistula lesion development. Dr. Greg Hundley: Now, metabolomics, lipidomics, functional metabolic assays and single cell analysis of cultured human macrophages revealed that PPAR alpha modulates macrophage glycolosis, citrate metabolism, mitochondrial membrane sphingolipid metabolism and heterogeneity. Dr. Carolyn Lam: Okay. So what is the take home message Greg? Dr. Greg Hundley: Right Carolyn, thought you would ask me that. Dr. Greg Hundley: So PPAR alpha activation suppresses the development of vein graft and arterial venous fistula lesions. And PPAR alpha reduces macrophage activation by influencing macrophage heterogeneity, mitochondrial integrity, and the metabolome. So Carolyn, given that peripheral arterial disease and chronic kidney disease prevalences are increasing, warranting needs for more vein grafts and arterial venous fistulas, this target discovery platform is applicable to investigating therapies for these diseases. Dr. Greg Hundley: And a really nice accompanying editorial is provided by doctors Reilly and Bornfeldt. Dr. Greg Hundley: Well Carolyn, how about we turn to look at what is in the mailbag this week? Dr. Carolyn Lam: Well let me tell you about it Greg. We've got a cardiovascular case series by Dr. Borlaug on things are not always as they seem, multimodality exercise assessment and evaluation of dyspnea. In cardiology news by Kuhn there's a discussion of Evinecumab approval adds a new option for homozygous familial hypercholesterolemia with a hefty price tag. A perspective piece by Dr. Watkins on time to think differently about sarcomere negative hypertrophic cardiomyopathy. And finally a research letter by Dr. Ahn on reduction in Kawasaki disease after non-pharmaceutical interventions in the COVID-19 era, a nationwide observational study in Korea. Dr. Carolyn Lam: Wow. That wraps it up for the summaries. Let's go on to the feature discussions shall we, Greg? Dr. Greg Hundley: You bet. Dr. Carolyn Lam: We are about to talk about the extended follow-up results of the PRADA trial. Oh, so interesting. So happy to have with us today, doctors Geeta Gulati and Dr. Torbjørn Omland, both from the Akershus University hospital in Norway, and you would probably recognize that Dr. Torbjørn Omland is also one of our associate editors, but both here are the co-corresponding authors of this beautiful paper. Dr. Carolyn Lam: Thank you so much for coming here today. Torbjørn, maybe you could start with what is the PRADA trial? Why did you decide to do an extended follow-up? Dr. Torbjørn Omland: Yeah so PRADA was a two times two factorial randomized double blind clinical trial that sought to evaluate the effects of intervention with receptor blocker Candesartan. And a beta blocker Metoprolol in patients with early breast cancer who received anthracycline therapy as part of their chemotherapy. And then we wanted to assess the effect of this sort of preventative therapy, left ventricular function and injury. Dr. Torbjørn Omland: So we reported the primary results of the trial a few years ago and showed that intervention with Candesartan most associated with a significant elevation of the reduction in left ventricular ejection fraction that these patients may experience, and also that treatment with the beta blocker Metoprolol was associated with an intimation of the increase in cardio proponents suggesting a beneficial effect on myocardial injury. However, whether these results were or these effects were sustained after termination of the study drugs was unknown. And that was what we really wanted to address with extended follow-up study. Dr. Carolyn Lam: Yeah, makes a lot of sense, especially because these injuries I suppose could still continue. And just to be very clear, the medications though were only taken during the adjuvant chemotherapy and therefore could be a variable duration from what I understand. Right? Great. Dr. Carolyn Lam: So Geeta then, could you tell us what did the extended analysis show? Dr. Geeta Gulati: The extended follow-up was interesting and it was something we really wanted to figure out because there are not many studies who have been done on the extended follow-up and you're not giving these study medications afterwards. Dr. Geeta Gulati: So very interestingly we saw that the decline in the ejection fraction was still there in the whole group. But this time there was no difference in the group who received Candesartan do those who didn't. And we show that there was a different in the primary results, but now in the extended follow-up there was no difference. And then also in the Metoprolol group that had previously shown that there was lesser rise in the troponins. Again, there was no difference in the groups now on the extended follow-up. Dr. Geeta Gulati: So this is very interesting because this shows that there is a small, modest decline in a left ventricular ejection fraction during and after the breast cancer therapy. But what does this really mean? It's a small decline and it's within the normal range and the cardioprotection is not working. So, are we perhaps looking at the wrong group? Perhaps we should look at patients who have the higher cardiovascular risk factors. Perhaps even we should look at more novel heart failure or cardiac drugs that may have a stronger effect on the ejection fraction. Dr. Carolyn Lam: Right. So Geeta though, can we unpack that a little bit? You see, the patients were not on the medication anymore at the time of follow-up. So you're saying that even though they were given adjuvant chemotherapy and covered with the drug, that even not having any more chemotherapy, their ejection fraction still fell. And if I'm not wrong, this was an MRI analysis. And so it was only by an ejection fraction of two percent on mean fall, right? How do we think about that clinically? Dr. Geeta Gulati: And that's the important question, isn't it? Because a decline in the ejection fraction of less than two percent within the normal range, what does it really mean? Well initially we thought that if there was a different in those who had cardioprotective medication compared to those that didn't, it may prevent development of further decline in the cardiac function and then heart failure in the future. But now, there is really no difference between the groups. So perhaps the clinical implication of giving cardio protection to all cancer patients is not really that useful. Perhaps they should look at those who are at higher risk because they would have a greater fall in ejection fraction and then more cardioprotective effect of these drugs. Dr. Carolyn Lam: Yeah, totally. And perhaps the metrics that we're used to seeing in the past with greater falls of ejection fraction, maybe it just doesn't apply currently or perhaps with the specific chemotherapeutic regimens perhaps that you're using now. Because with a very small fall, and I believe you only had one heart failure event, right? If I'm not wrong in this extended follow-up. So, just to let the audience know, it was very small fall, little number of events. It's hard to really tease apart what that clinically means. Now, could I ask though, does it mean we need actually a more sensitive marker? Because there was some interesting stuff about global longitudinal strain. Could you- Dr. Geeta Gulati: I would throw that question back to Torbjørn I think. Dr. Torbjørn Omland: Yes. So that's a very interesting question Carolyn. So we did observe what seemed to be a beneficial, but a sort of minor effect on global longitudinal strain. So we know that that is the more sensitive index of systolic function than left ventricular ejection fraction, that was the pre defined primary outcome. So that's raises of course questions whether a future trial should more focus on these more sensitive indices of cardiac function. Dr. Carolyn Lam: Yeah. Geeta, could I then really put it back to you? And the tough question I always get, how do we apply these results clinically then? I mean, you see these patients right? Now what? Do you give or do you don't give? And which one do you give? And how do you identify high risk patients? I don't know. Dr. Geeta Gulati: Again, I think all the patients are unique aren't they? So that's where we have to start. So in my clinic, if I have a high risk patient with hypertension, diabetes, hypercholesterolemia, yeah perhaps they even have had a cardiovascular disease before something like this. Then I will take more care of these patients and be more careful with the echo measurements I'm doing and if I find that they have a decline in their cardiac function, I may be more eager to start them on cardioprotective medication. Dr. Geeta Gulati: But then in R-Regen we follow all the HER two positive breast cancers with echo. If I don't have echoparamaties that clearly tells me that they have a decline in the cardiac function, then I may wait to start cardio protection because none of the studies has really so far show that all patients should have these cardioprotective medication or prevention. Dr. Carolyn Lam: Nice. Thank you. That was a tough one to get at. And I suppose Torbjørn I have to give you another tough one then. Because how to address the remaining unanswered questions, right? Because one of them on my mind too, is how to identify the high risk, do biomarkers play a role? And then the other is if we then start the preventive therapies like ERBs and beta blockers, should we actually continue it forever? And so on. But anyway Torbjørn please, please, what does the future hold? Dr. Torbjørn Omland: I think it's worthy of a recap or underscoring that these are really good news for many breast cancer patients that actually the risk of an important decline in ventricular function is lower than we thought. So that may be because of several things. I think in general, those whose used these cardiotoxic drugs are lower. And we also, I think that there's increased collaboration between oncologists and cardiologists. Also meaning that we are better to pick up the high-risk patients at an early stage. Dr. Torbjørn Omland: But of course, it's very important questions that you asked regarding how to identify the high risk patients. And I think that's where really future research should focus. So there we know that traditional risk factors are important. We are looking into whether biomarkers can be used, if there's more sensitive imaging in this can be used. But so far we haven't really succeeded in getting the risk model that really identifies it on the patient level. So that's work that remains to be done. Dr. Torbjørn Omland: And then we are also looking for new types of intervention, good exercise, good other drugs. We are doing now a PRADA two study where we look at the effects of Sacubitril Valsartan in this setting. And those are also very exciting, I think, and we look very much forward to present that in the future. Dr. Carolyn Lam: Oh wow thank you so much Torbjørn and Geeta. The PRADA two trial. I've got to ask you, why do you then call it the Chanel trial? But I think I'll save that for another day. So thank you. Thank you once again, this is fabulous and congratulations to you both. Dr. Torbjørn Omland: Thank you. Dr. Geeta Gulati: Thank you. Dr. Greg Hundley: Well listeners, welcome to our second feature discussion today. And we have with us Dr. Marc Dweck from University of Edinburgh in Scotland and our own associate editor, Victoria Delgado from Leiden in the Netherlands. Welcome to both of you. Dr. Greg Hundley: Marc, we're going to get started with you. Could you tell us a little bit about the background for your study and what was the hypothesis that you wanted to test? Dr. Marc Dweck: Thanks very much Greg for the invitation. So I guess aortic stenosis is perhaps the last major cardiovascular condition where we don't have a medical therapy. We're unable to treat these patients. We're unable to prevent progression. We're only left with a valve replacement. And so we, like a lot of groups around the world, want to develop a treatment for aortic stenosis. Our group did the first SALTIRE trial, where we looked at statins seeing if we could slow aortic stenosis progression. And that, like similar trials, was neutral. No effect on the valve progression. Dr. Marc Dweck: And so actually I've spent the last 10 years looking at some of the factors associated with aortic stenosis progression in particular. The answers that we've had from those trials have kind of come back telling us that really it's a process of calcification. If you look at what triggers progressive valve narrowness is this calcific process, that seems to be a self perpetuating disease. Dr. Marc Dweck: So the question is, how do you target this calcification process? How can you interrupt it? And how can you do that without compromising bone health in these elderly patients? So in trying to come up with a solution to that we thought about using osteopetrosis agents, which we hypothesized would maintain both bone health and reduce vascular calcification on the basis of observational data and also animal data suggesting that. And that was really where we came from in the design of the SALTIRE two trial. Dr. Marc Dweck: And doing a big trial with clinical endpoints wasn't felt to be feasible and instead we decided to look at imaging end points and see whether we could slow disease progression using these agents. Dr. Greg Hundley: Very nice Marc. And so you're really leading us into, tell us a little bit more about your study population and your study design. Dr. Marc Dweck: Yeah so we wanted to take patients from our outpatient clinic with mild, moderate and even early severe disease, asymptomatic patients crucially, patients that aren't scheduled for aortic valve replacement and see the effects of these drugs on disease progression. Dr. Marc Dweck: So we did a randomized control trial. There was three arms. Patients were randomized to Alendronate, Denosumab, these are the two osteopetrosis agents, or placebo. We then did a series of baseline imaging tests. So the primary end point was based on CT calcium scoring. So they had a baseline CT calcium score. They also had a baseline echocardiogram and they had a baseline fluoride PET scan. So this measures calcification activity in the valve. And then we essentially repeated those tests after a period of time on the drugs, or on placebo. We repeated the calcium score and the echo after two years and repeated the PET scan after one year. Dr. Greg Hundley: Very nice, and so before you tell us your results, a little bit, how many patients? And maybe their average age and the rough distribution of men versus women. Dr. Marc Dweck: Yeah so study recruited roughly 50 patients in each arm. The average age was 72 and there was 21% females in the study. So, like a lot of studies in aortic stenosis, a low female prevalence. Despite our best efforts, that's something we need to attend to in the future, but otherwise, a representative age group and patients with this disease. Dr. Greg Hundley: And what did you find? Dr. Marc Dweck: Well we found that the drugs didn't have an effect on any of these imaging assessments. So, there was no effect on the progression for CT calcium score at two years, no effects on any of the echocardiographic assessments of hemodynamic severity, and no effect on calcification activity as measured with the fluoride. Dr. Marc Dweck: So a very consistent result using multiple different imaging modalities, which I think gives us confidence that there isn't at least a dramatic effect of these drugs on disease activity or disease progression, in aortic stenosis. Dr. Greg Hundley: Very good. Well listeners, we're now going to turn to one of our associate editors, Dr. Victoria Delgado, and she is really a valvular heart disease expert member of our team. Dr. Greg Hundley: Victoria, I know you see a lot of papers that kind of come across your desk. What attracted you to this manuscript? And then how do you put the results in the context of other research that's going on to halt the progression of aortic stenosis. Dr. Victoria Delgado: Thank you Greg. So first the first thing that attracted my attention for this article is the question. We know that we don't have any medical therapy for halting the progression of aortic stenosis. And even if the previous studies have been negative or neutral, still there is the interest of trying to find a less invasive therapy for these patients, or even prevent that they arrive to surgical or transcatheter aortic valve replacement. Dr. Victoria Delgado: And the second is that these are very strong analysis because it's a randomized clinical trial and using as end points imaging. So that trial also in a way answers the question of which imaging technique we need to use in order to see the effects of specific therapies. Previous studies have used mainly echocardiography, but that only gave us information on the modynamic effects of the aortic stenosis. While in this study, we have the combination of CT and a combination of a PET that he give us also information on how the calcification is happening. So that makes the study very comprehensive and give us more insights into this pathophysiology, to this pathology particularly. Dr. Greg Hundley: Very nice. So it sounds like looking at aortic stenosis from multiple different angles, whether it be echocardiography or perhaps imaging processes that look at the progression of calcification. Dr. Greg Hundley: Well, Marc, I want to come back to you. What do you think is the next, sounds like you've been working in this area for an extended period of time. What do you see as the next research study that you and your group may undertake in this area? Dr. Marc Dweck: I Think we've got the study design about right. I think if in the future studies we want to do, I think we would adopt a similar design using these imaging end points. Dr. Marc Dweck: I have to say I'm very influenced by the recovery trial that has been conducted in the UK with COVID. I mean, here's a disease where we wanted to get a treatment as quickly as we can. And in doing that, developing a platform type trial where you potentially test multiple different promising agents simultaneously across multiple centers across the world or the UK, I think that would be the quickest way to developing a treatment. And so I'm encouraged that there are five or six very good targets where we could, for a new therapy in aortic stenosis. And I think a platform type design where we engage multiple groups using imaging as that initial end point. And then, the drugs that appear to have an effect on these imaging end points we can start to recruit more patients at those sites, into those centers, looking for clinical end points. Dr. Marc Dweck: I think that kind of discussion is happening around the world now between groups that are interested because we want to crack this problem quickly. We don't want to wait and do these different studies sequentially. We want to try and do them simultaneously. And I'm excited about that. I think if we do that, we've got a real shot at developing a treatment over the next five to 10 years say. Dr. Greg Hundley: Fantastic. Dr. Greg Hundley: And Victoria, I know you have interest in this particular area. Do you have anything you'd like to add? Dr. Victoria Delgado: Yeah. I think that those studies that Mark said are really welcome and I hope that they are positive. And give us a little bit of more to treat these patients. My main fear is that these patients are not as frequent, for example, as heart failure patients. Where we have several therapies where we have possibility to enroll patients in trials for new drugs, that we know that probably are going to be effective. But for valvular heart disease it has been always the end point to reach surgery or to reach an aortic valve replacement or indication of the mitral valve and mitral valve repair. So in early phase of the disease, my main concern is that maybe the patient is not going to be well-trained to understand what are the consequences. I want to always wait until maybe when is needed for the surgical or transcatheter procedure. Dr. Victoria Delgado: But I think that increasing the awareness of the prevalence of valvular heart disease and the consequences may help people to understand, to put more attention for an early diagnosis and develop new drugs that can help, like in this case, aortic stenosis one of the most frequent valvular heart disease, to prevent the proliferation and to prevent the replacement of the valve. Dr. Greg Hundley: Very nice. Well listeners, this has been a wonderful discussion and we greatly appreciate the input that we've been able to gather today from Dr. Marc Dweck from Edinburgh in Scotland and our own associate editor, Dr. Victoria Delgado. Bringing this information from a randomized trial, evaluating osteoporosis drugs, and really indicating they did not disrupt the progression of calcification in patients with aortic stenosis. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, we want to wish you a great rest of your week and we will catch you next week on The Run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.  

Commentary by Dr. Edward Gerstenfeld

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

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, 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.

2020年11月2日 星期一 第1期FDA 淀粉样变心肌病的新药上市LANCET 肾去神经支配术治疗高血压的新研究Science Advance 四维心脏补片治疗缺血性心肌病他法米迪（tafamidis）2019年5月，他法米迪（tafamidis）被FDA批准用于治疗家族性或野生型甲状腺素运载蛋白介导（ATTR型）的淀粉样变心肌病。淀粉样变心肌病是一种淀粉样原纤维在心脏细胞外区沉积导致的疾病，其中约95%是由甲状腺素运载蛋白介导的（ATTR型）、或由免疫球蛋白轻链介导的（AL型）。淀粉样变性可累及多个脏器，其中心脏受累可导致心力衰竭、心律失常和死亡。他法米迪在甲状腺素结合位点与甲状腺素运载蛋白结合，稳定化合物、防止四聚体分离和淀粉样物质生成。《ATTR-ACT研究：他法米迪治疗ATTR型淀粉样变心肌病》New England Journal of Medicine，2018年9月 (1)这个多中心、国际、双盲、安慰剂对照、3期试验中，纳入441名患者ATTR型淀粉样心肌病患者，分别接受他法米迪80mg、他法米迪20mg或安慰剂治疗30个月。接受他法米迪治疗的患者的全因死亡率和心血管相关的住院率显著低于安慰剂组（P

2020年11月2日 星期一 第1期FDA 淀粉样变心肌病的新药上市LANCET 肾去神经支配术治疗高血压的新研究Science Advance 四维心脏补片治疗缺血性心肌病他法米迪（tafamidis）2019年5月，他法米迪（tafamidis）被FDA批准用于治疗家族性或野生型甲状腺素运载蛋白介导（ATTR型）的淀粉样变心肌病。淀粉样变心肌病是一种淀粉样原纤维在心脏细胞外区沉积导致的疾病，其中约95%是由甲状腺素运载蛋白介导的（ATTR型）、或由免疫球蛋白轻链介导的（AL型）。淀粉样变性可累及多个脏器，其中心脏受累可导致心力衰竭、心律失常和死亡。他法米迪在甲状腺素结合位点与甲状腺素运载蛋白结合，稳定化合物、防止四聚体分离和淀粉样物质生成。《ATTR-ACT研究：他法米迪治疗ATTR型淀粉样变心肌病》New England Journal of Medicine，2018年9月 (1)这个多中心、国际、双盲、安慰剂对照、3期试验中，纳入441名患者ATTR型淀粉样心肌病患者，分别接受他法米迪80mg、他法米迪20mg或安慰剂治疗30个月。接受他法米迪治疗的患者的全因死亡率和心血管相关的住院率显著低于安慰剂组（P

Commentary by Dr. Valentin Fuster

Commentary by Dr. Ana Barac

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 in the real time mapping of AF drivers RADAR study, Subbarao Choudry and associates examined in a single arm first in human investigator-initiated FDA IDE study, a novel system for real time, high resolution identification of atrial fibrillation, AF drivers, in persistent or long-standing persistent AF. They enrolled 64 subjects at four centers, 73% male age, 64.7 years, BMI 31.7. LA size 54. Longstanding AF, 83% longstanding persistent, 17%. prior AF ablation, 41%. After 12.6 months of follow-up, 68% remained AF free off all antiarrhythmics. 74% remained AF free and 66% remained AF, AT and A-flutter free on or off antiarrhythmic drugs. AF terminated with atrial fibrillation ablation in 35 patients, 55% overall. And in 23 out of 38, 61% of de novo ablation patients. For patients with AF termination during atrial ablation, 82% remained AF free and 74% AF, AT or A-flutter free during follow-up on or off antiarrhythmic drugs. Patients undergoing first time AFib ablation had higher rates of freedom from AF than the redo group. In our next paper, David Briceño and associates examined 19 consecutive patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic right ventricular cardiomyopathy, ARVC, with procedures separated by at least nine months and a mean of 50 months. The authors found there was no significant progression of voltage bipolar 38 centimeters squared versus 53 centimeters squared, p=0.09 or unipolar 116 centimeters squared versus 159 centimeters squared, p=0.36 for the entire group. There was a significant increase in right ventricular RV volumes, percentage increase 28%. 206 milliliters versus 263 milliliters, P less than 0.001 for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume, p=0.006 for bipolar and p=0.03 for unipolar. Most patients with progressive RV dilatation, 57%, had moderate in two patients or severe in six patients, tricuspid regurgitation recorded either at initial or repeat ablation procedure. The authors found that in patients with ARVC presenting with recurrent ventricular tachycardia, more than 10% increase in right ventricular endocardial surface area of bipolar voltages consistent with scar is uncommon during intermediate follow-up. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. In our next paper, Susan Heckbert and associates examined detection of atrial fibrillation in 1,556 individuals participating in an ancillary study involving ambulatory ECG monitoring part of the cross-sectional analysis in the multiethnic study of atherosclerosis, MESA, a community based cohort study that enrolled 6,814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. Among 1,556 participants, 41% were white, 25% African American, 21% Hispanic, 14% Chinese, 51% were women mean age 74 years. The prevalence of clinically detected atrial fibrillation after 14.4 years follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics and 9.9% in Chinese and was significantly lower in African Americans than in whites in both unadjusted and risk factor adjusted analyses, p less than 0.001. By contrast, in the same individuals, the proportion of monitor detected atrial fibrillation using a 14-day ambulatory ECG monitor was similar in the four race or ethnic groups. 7.1%, 6.4%, 6.9% and 5.2% compared with white, all p greater than 0.5. The authors concluded that the prevalence of clinically detected atrial fibrillation was substantially lower in African Americans than white participants with or without adjustments for atrial fibrillation risk factors. However, unbiased atrial fibrillation detection by ambulatory monitoring the same individuals reveal little difference in the proportion with atrial fibrillation by race, ethnicity, supporting the hypothesis of differential detection by race, ethnicity in the clinical recognition of atrial fibrillation. In our next paper, Maria Teresa Barrio-Lopez and associates examined the presence of epicardial connections between pulmonary veins and other anatomical structures. The authors considered an epicardial connection was present if one, the first pass around the pulmonary vein antrum did not produce pulmonary vein isolation. And two, subsequent atrial activation during pulmonary vein pacing showed that the earliest site was located away from the ablation line and later activation sites were obscured near the ablation line. Out of the 534 patients included, 72 or 13.5%, were found to have 81 epicardial connections. There was a significant association between the presence of epicardial connections in structural heart disease, 15.3% in patients without epicardial connections versus 36.5% in patients with epicardial connections, p less than 0.001. In patent foramen ovale, 4.6% versus 13.5%, p=0.002. The presence of a left common trunk was significantly associated with the absence of epicardial connection. 29.6% in patients without epicardial connections versus 16.2% in patients with epicardial connections, p=0.014. Patients with epicardial connections had a lower acute success of pulmonary vein isolation compared to patients with epicardial connection, 99.1% versus 86.1%, p less than 0.001. After adjusting for age, sex, type of atrial fibrillation, left atrial area, hypertension, structural heart disease, presence of left common trunk, patent foramen ovale and time for atrial fibrillation and diagnosis to the ablation, the authors found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with epicardial connections compared to patients without epicardial connections, hazard ratio 1.7, p=0.04. In our next paper, Benzy Padanilam and associates examined the role of premature His complexes to differentiate AV nodal reentry tachycardia from atrioventricular reentry tachycardia high output pacing at the distal His location delivered premature His complexes. Atrioventricular reentrant tachycardia was predicted when late premature His complexes perturbed tachycardia or when early premature His complexes led to atrial advancement by amount equal or greater than the degree of premature His complex prematurity. Among the 73 SVTs, the test accurately predicted atrioventricular reentry tachycardia, n=29 in AV nodal reentry tachycardia, n=44 in all cases. Late premature His complexes advanced the circuit in all 29 atrioventricular reentry tachycardias in none of the AV nodal reentry tachycardias, sensitivity and specificity 100%. With earlier premature His complexes, the degree of atrial advancement was equal or greater than the premature His complex prematurity in 26 out of 29 atrioventricular reentrant tachycardia and none of the AV nodal reentrant tachycardias, 90% sensitivity and a 100% specificity. The mean prematurity of the premature His complex required to perturb AV nodal reentry tachycardia was 48 milliseconds, range 28 to 70 milliseconds. And the advancement less than the prematurity of the premature His complex, mean 32 milliseconds range, 18 to 54 milliseconds. In our next paper, Masateru Takigawa and associates examined the recurrence rate and mechanisms of atrial fibrillation ablation related atrial tachycardia recurrence among 147 patients with atrial tachycardias treated with arrhythmia system. 46.3% had recurrence at a mean of 4.2 months and 44 patients received a redo procedure. Atrial tachycardia circuits in the first procedure were compared to those in the redo procedure. Although mappable atrial tachycardias were not observed in seven patients, 68 atrial tachycardias were observed in 37 patients during the first procedure, perimitral flutter in 26 patients, roof-dependent macroreentrant atrial tachycardia in 18, peritricuspid flutter in 10, non-macro atrial tachycardia in 14 and focal atrial tachycardia in three. During the redo atrial tachycardia procedure, 54 atrial tachycardias were observed in 41 patients, perimitral flutter in 24, roof-dependent macroreentrant atrial tachycardia in 14, peritricuspid flutter in one, non-macroreentrant tachycardia in 14, and focal atrial tachycardia in one. Recurrence of perimitral flutter and roof-dependent macroreentrant atrial tachycardia were observed in 57.7% and 44.4% respectively, while peritricuspid flutter did not recur. Either the same focal atrial tachycardia nor the same non-macroreentrant tachycardia were observed except in one case with septal scar related to biatrial tachycardia. Epicardial structure related to atrial tachycardia were involved in 18 out of 24 or 75% in perimitral flutter, in 28.6% in roof-dependent macroreentry atrial tachycardia, in 28.6% in non-macroreentry tachycardia. Out of the 21 patients with a circuit including epicardial structures, six patients treated with ethanol infusion in the vein of Marshall did not show any atrial tachycardia recurrence although 53.3% treated with radiofrequency showed atrial tachycardia recurrence, p=0.04. In our next paper, Yaya Yu, Xuecheng Wang and associates compared the incidence and characteristics of ablation related asymptomatic cerebral emboli between high resolution diffusion weighted DWI and conventional DWI image. They examined 55 consecutive atrial fibrillation ablation patients undergoing high resolution DWI one day prior to ablation and repeated high resolution DWI and conventional DWI within 48 hours of post ablation. The authors found that high resolution DWI revealed a higher incidence of acute asymptomatic cerebral emboli compared to conventional DWI, 67.3% versus 41.8%, p less than 0.001. And significantly more asymptomatic cerebral emboli, 106 versus 45 lesions, p=0.001. For asymptomatic cerebral emboli, seen on both scans, the size measured by high resolution DWI was larger, 5.42 versus 4.21 millimeters, p less than 0.001. No patients had any impaired neurocognitive performance during follow-up. Impaired left ventricular ejection fraction, p=0.012 and low interoperative activated clotting time ACT p=0.009, level was associated with occurrence of asymptomatic cerebral emboli in a multivariate analysis. In our next paper, Ahmed AlTurki and Mariam Marafi and associates performed a systematic review and meta-analysis to assess the risk of stroke, myocardial infarction and death following postoperative atrial fibrillation after non-cardiac surgery. The authors included 28 studies, enrolling 2,612,816 patients in their final analyses. At one month, in ten studies, postoperative atrial fibrillation with associated with approximately three-fold increased risk of stroke, odds ratio 2.82, p less than 0.001. Postoperative atrial fibrillation was associated with ≈4-fold increase in the long-term risk of stroke, odds ratio 4.12, p ≤ to 0.001. In eight studies with 12 months or greater follow-up, there was a significant increase in the risk of stroke and myocardial infarction associated with postoperative atrial fibrillation, odds ratio 3.44, p value, p less than 0.001. And odds ratio for myocardial infarction 4.02, p less than 0.001. Postoperative atrial fibrillation was associated with a threefold increase in all of cause mortality 30 days, 15.0% versus 5.4%, odds ratio 3.36. In a research letter, Zhiyong Qian, Xiaofeng Hou, Yao Wang and associates validated physiological left bundle branch block pacing using high density ventricular mapping in a swine model. In another research letter by Shinsuke Miyazaki and associates, the authors examined whether the durability of pulmonary vein isolation can be predicted by the time to isolation in second generation cryoballoon ablation. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.  

Commentary by Dr. Valentin Fuster

JACC: Case Reports - Audio Summary by Dr. Julia Grapsa

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

This week we speak with Dr. Douglas Mah, Assistant Professor of Pediatrics - Harvard Medical School and Director of the Pacemaker and ICD Service at Children's Hospital Boston about a recent paper he published with his colleagues on coronary artery compression from epicardial pacemaker leads. Who is at risk for this rare complication? How can patients be screened? Once identified, what is the treatment? We review all this and more with Dr. Mah. doi: 10.1016/j.hrthm.2018.06.038

This week we speak with Dr. Douglas Mah, Assistant Professor of Pediatrics - Harvard Medical School and Director of the Pacemaker and ICD Service at Children's Hospital Boston about a recent paper he published with his colleagues on coronary artery compression from epicardial pacemaker leads. Who is at risk for this rare complication? How can patients be screened? Once identified, what is the treatment? We review all this and more with Dr. Mah. doi: 10.1016/j.hrthm.2018.06.038

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

This week we delve into the world of novel means for epicardial pacing and defibrillation in small children or those with congenital heart disease. Dr. Bradley Clark of The Children's Hospital at Montefiore and Dr. Yaniv Bar-Cohen of Children's Hospital of LA discuss their recent works on developing minimally invasive epicardial pacing and defibrillation in infants and those with congenital heart disease. The ability to provide epicardial pacing or defibrillation without the need for a surgical incision is exciting and both experts speak of the challenges and future of this important work.

This week we delve into the world of novel means for epicardial pacing and defibrillation in small children or those with congenital heart disease. Dr. Bradley Clark of The Children's Hospital at Montefiore and Dr. Yaniv Bar-Cohen of Children's Hospital of LA discuss their recent works on developing minimally invasive epicardial pacing and defibrillation in infants and those with congenital heart disease. The ability to provide epicardial pacing or defibrillation without the need for a surgical incision is exciting and both experts speak of the challenges and future of this important work.

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

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

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

Cardiac surgery can vary from being routine elective surgery to time-critical emergency surgery. The term encompasses a broad range of procedures carried out on patients from neonates to nonagenarians. In the 63 years since the first open heart surgery was performed using cardiopulmonary bypass enormous advances have been made in the field such that an average person presenting for coronary bypass grafting in 2016 can expect a very low chance of peri-operative morbidity or mortality. When things go wrong however they can go badly wrong and at the worst possible moment (see Murphy’s Law). This talk focuses on describing common complications encountered in the postoperative period, with a focus on anticipation, prevention and planning for rapid recognition and successful management of potentially life threatening complications.