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Welcome to EP Edge Journal Watch — where cardiac electrophysiology meets evidence, precision, and perspective.
Hosted by Dr. Niraj Sharma, this bi-weekly podcast distills high-impact cardiovascular and EP research into clear, clinically meaningful insights. Each episode goes beyond headlines and abstracts to uncover what new studies actually mean for patient care, decision-making, and the future of electrophysiology.
What EP Edge Journal Watch stands for:
Evidence-based practice
Precision electrophysiology
A forward-thinking, edge-driven approach to how we interpret and apply data in real-world clinical settings.
Whether you’re an electrophysiologist, cardiologist, researcher, trainee, or allied health professional, EP Edge Journal Watch brings you the signal — not the noise. Expect sharp summaries, thoughtful commentary, and practical takeaways designed for the busy clinician who wants to stay ahead of the curve
This program is for educational purposes only and reflects independent editorial commentary. It is not medical advice and should not replace clinical judgment or review of primary sources and guidelines. The views expressed are those of the host and contributors.
Niraj Sharma:Hello and welcome back to EP Edge Journal Watch. I am Doctor. Sharma and I am very glad you are here. Before we get into this issue I want to say thank you. Thank you for listening, thank you for reading and thank you especially for the thoughtful suggestions that many of you have been sending in.
Niraj Sharma:I do read them, I do value them, and they absolutely help shape the direction of this series. This issue was originally scheduled for release in March 2026, but with the arrival of the CHAMPION AF trial, the schedule changed. A special focus on that major trial took priority and as a result this issue has been pushed from March into April. Even so, the content of this issue remains highly important, sitting right at the intersection of electrophysiology, heart failure, ablation safety and structural intervention. We are going to cover five studies but really the larger theme is this: when new technology looks elegant, exciting or intuitively superior, does the evidence actually hold up when we test it against careful contemporary care?
Niraj Sharma:We begin with a major randomized reassessment of left atrial appendage closure versus physician directed medical therapy in older high risk atrial fibrillation patients. Then we move into two randomized CRT trials that point in different directions on conduction system pacing versus biventricular pacing. After that we look at mechanistic safety data on cerebral microembolization during pulsed field ablation. And finally we close with a highly practical study on who is most likely to need a permanent pacemaker after valve in valve TAVR. As always, I will walk through why the study was done, how it was designed, what the key numbers were, and then most importantly, what I think the practical EP Edge take is for day to day clinical thinking.
Niraj Sharma:So let's get started with the first paper, CLOSURE AF. CLOSURE AF asks a very important and very uncomfortable question. Left atrial appendage closure has often been positioned as an attractive alternative for older atrial fibrillation patients who are at high bleeding risk or who seem poorly suited for long term anticoagulation. The appeal is obvious. Seal off the appendage, reduce embolic risk, and maybe avoid the bleeding burden of chronic oral anticoagulation.
Niraj Sharma:But the real question is not whether we can close the appendage, the real question is whether doing so actually performs as well as or better than current physician directed medical care in the kind of high risk patients where this strategy is often discussed. This was a pragmatic, prospective, open label, multicenter, randomized trial performed across 42 German sites with experience in left atrial appendage closure. Nine twelve patients were randomized and the primary analysis included four forty six patients assigned to appendage closure and four forty two assigned to best medical care. This was an elderly and very high risk population. Mean age was just under 78 years.
Niraj Sharma:Mean CHADS VASc score was 5.2 and mean Hasbled score was three point zero. In the medical arm, most patients (about eighty five percent were treated with a direct oral anticoagulant. The primary endpoint was broad and clinically relevant. Stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death analyzed as a non inferiority time to event comparison with a hazard ratio margin of 1.3. Median follow-up was three years.
Niraj Sharma:The headline result is clear: left atrial appendage closure failed to demonstrate non inferiority. A first primary endpoint event occurred in one hundred and fifty five patients in the device arm versus one hundred and twenty seven in the medical therapy arm, with incidence rates of sixteen point eight versus thirteen point three per one hundred patient years. The difference in restricted mean survival time was -0.36 years and the non inferiority p value was 0.44. When you look at the individual components, the expected advantage still did not materialize. Stroke counts were identical, 27 events in each group, translating to 2.6 versus 2.7 per 100 patient years.
Niraj Sharma:Major bleeding was not reduced with appendage closure, it was numerically higher, 70 events versus 61 or 7.4 versus 6.2 per 100 patient years. Cardiovascular or unexplained death was also numerically higher in the closure arm, ninety nine versus eighty one. And although procedural success was high among attempted implants, the early procedural price was real. Major bleeding events, tamponade, device embolization requiring surgery, and even deaths were seen in the periprocedural window. So what do we do with that?
Niraj Sharma:The EP Edge take is that closure AF is a clinical reset. This was not appendage closure versus no therapy. It was appendage closure versus contemporary physician directed care in very elderly, very high risk atrial fibrillation patients, and in that setting closure did not buy a stroke advantage, did not buy a bleeding advantage, and certainly did not produce a cleaner overall outcome signal on the composite endpoint that most closely reflects how these patients actually live and die. In practice that means best individualized medical therapy remains the default strategy for most patients in this lane. Appendage closure may still have a role but it should be a selective strategy, not a reflexive escape hatch from anticoagulation.
Niraj Sharma:This trial should also sharpen how we consent patients. If the main argument being made is that a device simply feels safer than anticoagulation in an older bleeding prone patient, this study tells us that assumption needs to be challenged directly. Shifting gears. The next two studies stay in the randomized lane but now shift to CRT, where the signal becomes much more complicated. The heart sync left bundle branch pacing trial is the strongest randomized argument in favor of left bundle branch pacing as a resynchronization strategy.
Niraj Sharma:Cardiac resynchronization therapy has traditionally been the domain of biventricular pacing, but left bundle branch pacing offers something conceptually appealing. Instead of coordinating contraction by pacing both ventricles from separate sites, you try to restore physiologic activation by directly engaging the His Purkinje system, especially in patients with true left bundle branch block. Heart sync left bundle branch pacing was a prospective multicenter randomized clinical trial conducted at six centers in China. Two hundred patients with heart failure, left ventricular ejection fraction of thirty five percent or less, New York Heart Association class II through IV symptoms, and complete left bundle branch block were randomized one to one to left bundle branch pacing or biventricular pacing. The primary endpoint was time to all cause death or heart failure hospitalization.
Niraj Sharma:Secondary endpoints included death, heart failure hospitalization, echocardiographic response, and super response. Implant success was high in both groups, ninety eight percent in the left bundle branch pacing arm and ninety four percent in the biventricular arm. Median follow-up was thirty six months. The results strongly favored left bundle branch pacing. The primary endpoint occurred in eight percent of patients with left bundle branch pacing versus twenty eight percent with biventricular pacing, with a hazard ratio of 0.26 and a p value less than 0.001.
Niraj Sharma:The difference was driven mainly by heart failure hospitalization, seven percent versus twenty eight percent, hazard ratio 0.23, mortality was numerically lower, two percent versus five percent, but the event count was small. Reverse remodeling also favored left bundle branch pacing. At six months, ejection fraction was forty five percent versus thirty nine point two percent, and at last follow-up it was forty seven point three versus forty one point five percent. Super response was better as well, fifty five percent versus thirty six percent. Pace QRS duration was shorter, pacing thresholds were lower, and no major complications were reported in the left bundle branch pacing group.
Niraj Sharma:The EP Edge take here is that heart sync left bundle branch pacing represents the best case scenario for physiologic pacing. The substrate was favorable, true left bundle branch block, and severe systolic dysfunction. The operators were experienced, success rates were very high and under those conditions left bundle branch pacing looked not just feasible but clinically superior, but that does not automatically mean every CRT program should flip its default approach tomorrow. It means something narrower and more useful. In the right patient with the right anatomy and the right level of operator expertise, left bundle branch pacing can be a very powerful first line resynchronization strategy.
Niraj Sharma:This is especially persuasive in programs that can consistently achieve true capture rather than merely placing a septal lead and hoping for the best and that brings us directly to the counterweight study PhysioSync HF. If heart sync shows what conduction system pacing can do under optimized conditions, PhysioSync asks what happens when that strategy is deployed in a broader more heterogeneous environment. This was an investigator initiated multicenter non inferiority randomized clinical trial across 14 hospitals in Brazil. One hundred and seventy three patients undergoing the index procedure were analyzed, eighty seven assigned to conduction system pacing and eighty six to biventricular pacing. Eligible patients had symptomatic heart failure, left ventricular ejection fraction of 35% or less and left bundle branch block.
Niraj Sharma:Median ejection fraction was 26% and median QRS duration was one hundred and eighty milliseconds. The primary endpoint was a hierarchical composite of all cause death, heart failure hospitalization, urgent heart failure visit, and change in ejection fraction at twelve months. Importantly, the conduction system pacing strategy was intentionally heterogeneous. Left bundle branch area pacing was preferred but fallback options included his bundle pacing, deep septal pacing or even adjunctive coronary sinus pacing when needed. That design decision is critical because the physiology depends on what you actually capture, not just where the lead tip ends up.
Niraj Sharma:And the results were sobering. Conduction system pacing failed non inferiority and was actually inferior to biventricular pacing for the primary endpoint with an odds ratio of two point three six. The time to event composite of death, heart failure hospitalization, or urgent heart failure visit was higher with conduction pacing (hazard ratio 2.3. All cause death occurred in twelve point six percent of conduction system pacing patients versus four point seven percent of biventricular pacing patients, with a hazard ratio of three point three six. Ejection fraction improved in both groups but follow-up ejection fraction still favored biventricular pacing (thirty five percent versus thirty nine percent ).
Niraj Sharma:Both groups improved in QRS duration, symptoms and natriuretic peptide profile, so this was not a story of total failure. It was a story of weaker clinical yield and a worse overall signal. Procedure related complications were also numerically higher with conduction system pacing, and there were three procedure related deaths in patients randomized to that strategy. The EP Edge take is that PhysioSync HF is the necessary reality check. Once conduction system pacing is delivered with mixed techniques, mixed experience and broader implementation conditions, the promise can erode quickly.
Niraj Sharma:Nearly one in five patients in the conduction system pacing arm ended up with deep septal pacing, which may not deliver the same benefit as true left bundle capture. So the lesson is not that physiologic pacing is a bad idea. The lesson is that execution matters enormously. For practice the synthesis of heart sync and physiosync is actually very useful. In expert programs with highly selected substrate and reliable true capture, left bundle branch pacing may outperform biventricular pacing.
Niraj Sharma:Outside those mature programs, biventricular pacing remains the safer benchmark. So the question is not which therapy is universally better. The better question is in whose hands, in which patients, and with what level of technical certainty. Next we move from resynchronization to ablation and specifically to the cerebral embolic signature of pulsed field ablation. Pulsed field ablation has been embraced for speed, tissue selectivity and a lower collateral injury profile, but the neurologic conversation has not gone away.
Niraj Sharma:It has simply shifted from obvious clinical stroke to quieter but potentially important questions about silent cerebral lesions and intra procedural microembolic burden. This study was designed to compare cerebral microembolization during high power short duration radiofrequency ablation and two different pulse field ablation systems while also identifying which parts of the procedure are most embolic. This was a prospective observational study of 56 consecutive first time atrial fibrillation ablation patients at a single high volume center in Berlin. Twenty eight underwent high power short duration radiofrequency ablation, fourteen underwent pulsed field ablation with a circular multi electrode array catheter, and fourteen underwent pulsed field ablation with a variable loop circular catheter. Note the flow rate used was constant four milliliters per minute.
Niraj Sharma:Continuous unilateral transcranial Doppler monitoring was used to detect microembolic signals in the middle cerebral artery. Those signals were assigned to specific procedural phases, transseptal puncture, catheter introduction, mapping, ablation, and catheter removal. Neurologic assessment, including NIH stroke scale, was performed before and after ablation. The results were striking and very platform specific. Total microembolic signal count was fourteen oh two for the variable loop pulse field catheter, four forty nine for the circular multi electrode pulse field catheter, and only 131 for radiofrequency ablation, with a p value less than 0.001 across groups.
Niraj Sharma:Ablation itself was the dominant embolic phase, accounting for 87% of all detected signals. Compared with radiofrequency ablation, ablation phase signals were roughly 4.1 fold higher with the circular multi electrode platform and 13.6 fold higher with the variable loop platform. Most patients remained neurologically intact by bedside exam, but two patients in the pulsed field arms developed new focal deficits with MRI confirmed acute infarcts. This is one of the more practically important pulsed field ablation safety papers because it breaks the habit of talking about PFA as though it were one single cerebral safety category. It is not.
Niraj Sharma:What this study suggests is that neurologic risk may be shaped by catheter design, tissue contact, energy delivery pattern and workflow details, not simply by the label of pulsed field ablation itself. There are limitations. This was a single center study. Monitoring was unilateral rather than bi hemispheric. There was no routine brain MRI in everyone and no long term neurocognitive follow-up.
Niraj Sharma:So we cannot equate microembolic signals directly with permanent clinical harm in every case, but we also should not dismiss them simply because the patient wakes up without an obvious stroke syndrome. The EP Edge take is straightforward. Do not generalize the neurologic safety profile of one pulse field platform to another. When evaluating PFA data in 2026, the right question is not merely Was PFA used? The right question is Which catheter?
Niraj Sharma:What lesion workflow? How was anticoagulation managed? And where in the procedure is the embolic burden actually being generated? Our final study is highly practical and moves into structural intervention. Predictors of permanent pacemaker implantation after valve in valve transcatheter aortic valve replacement.
Niraj Sharma:Valve in valve TAVR is increasingly used for failed surgical bioprostheses. Pacemaker rates are generally lower than in native valve TAVR, but when permanent pacing is required that has real consequences for length of stay, long term pacing dependency, and possibly survival. The real question is not simply whether pacemaker implantation occurs, the question is whether the risk is visible before or during the procedure. This Mayo Clinic study was a retrospective single center observational analysis of consecutive valve in valve TAVR procedures performed from 2012 through 2022. Two sixty one patients were analyzed and twenty four or nine point two percent underwent permanent pacemaker implantation before discharge.
Niraj Sharma:Clinical variables, baseline ECGs, echocardiographic data, and fluoroscopic implantation depth were reviewed and propensity matching was used to reduce confounding. Several predictors stood out very clearly. Pre procedural bifascicular block was a major signal, with an odds ratio of twelve point one five for permanent pacemaker implantation. Greater septal implantation depth also increased risk, with an odds ratio of one point two nine, reinforcing that implant depth is not just a technical detail but a potentially modifiable procedural factor. New post procedure bundle branch block was even more informative.
Niraj Sharma:New left bundle branch block carried an odds ratio of twenty three point five six and new right bundle branch block an odds ratio of twenty four point four for subsequent pacemaker implantation. Non femoral access also emerged as a predictor. By contrast, severe aortic regurgitation as the mechanism of prosthetic valve failure was associated with lower pacemaker odds. One of the more clinically interesting findings was what happened over time after device implantation. Ventricular pacing burden greater than ninety percent rose from twenty five percent at three months to more than fifty six percent at twelve months.
Niraj Sharma:That suggests many of these were not merely precautionary implants. A substantial fraction evolved into genuinely pacing dependent phenotypes. At a median follow-up of about nine sixty two days, adjusted mortality was also higher in the pacemaker cohort, though the confidence intervals were wide and the event count was modest. The EP Edge take is that the conduction system still matters very much in valve in valve transcatheter aortic valve replacement. What makes this paper useful is that the predictors are actionable.
Niraj Sharma:Baseline bifascicular disease should heighten concern before the case starts. Deep septal implantation is something operators can think about and potentially modify, and new bundle branch block after the procedure is not an incidental ECG curiosity. It is a warning signal. So in practice, this study supports tighter rhythm risk stratification careful attention to implantation depth during the procedure, and more disciplined post procedure monitoring when new conduction abnormalities appear. If a patient enters the case with baseline bifascicular disease and exits with new bundle branch block, that is someone who may already be on a real path toward permanent pacing.
Niraj Sharma:Before we close, let me quickly pull the issue together. Closure AF reminds us that left atrial appendage closure should not be assumed to outperform contemporary best medical therapy in older high risk atrial fibrillation patients. In this study, the bleeding advantage did not appear, stroke outcomes were not better, and early device related harms still mattered. Heart sync left bundle branch pacing shows what left bundle branch pacing can achieve when the substrate is right and the operators are highly experienced. In that environment physiologic pacing looked genuinely strong.
Niraj Sharma:PhysioSync HF delivers the caution. Once conduction system pacing is deployed with broader variability in technique and experience, the signal can shift, and biventricular pacing remains the safer benchmark for many programs. The Pulse Field Ablation Microembolization study tells us that cerebral safety is platform specific, not just energy source specific. We need to stop speaking about PFA as though all systems are neurologically interchangeable, and the valve in valve transcatheter aortic valve replacement study reminds us that conduction risk is still highly relevant in structural intervention. Bifascicular block, deeper septal implantation, and new bundle branch block are the red flags.
Niraj Sharma:All references and graphics are available on the LinkedIn newsletter, EP Edge Journal Watch as well as on Substack at epedge.substack.com. Comments and suggestions can be emailed to epedgecast.gmail . com. Thank you again for listening and thank you for the continued support and suggestions. I truly appreciate it. Until the next episode, take care and bye for now.