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Welcome to EP Edge Journal Watch, where cardiac electrophysiology meets evidence, precision, and perspective.
Hosted by Dr. Niraj Sharma, this weekly podcast distills high-impact cardiovascular and Cardiac Electrophysiology and arrhythmia 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, arrhythmias analysis
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 to EP Edge Journal Watch. I'm Doctor. Sharma. Thank you for listening and for bringing these discussions into your reading, teaching, and patient care. In a world where disagreement can quickly become division, international scientific collaboration offers another way forward: ask difficult questions together and remain willing to change your mind.
Niraj Sharma:This is Issue 36, our European Society of Cardiology Congress special issue. The meeting took place in Munich, Germany from August 28 through thirty one, twenty twenty six. Our monthly collaboration with the Heart Rhythm Society continues alongside this weekly series. The EP EDGE website is coming soon at epedge.org. Today's theme is AF ablation, sham controls and the meaning of success.
Niraj Sharma:We'll begin with the controversial and thought provoking PVI, sham AF, then revisit prior sham trials PFA sham and sham PVI. We'll examine what their different results tell us about symptoms, rhythm burden, and beta blockers. Then we'll turn to dual energy ablation, structured exercise, individualized substrate ablation, and edoxaban after intracranial hemorrhage. The central question isn't simply whether an intervention changes a rhythm recording, it's whether that change produces additional benefit that matters to the patient and at what cost in treatment burden and risk. Our lead paper is Rolf Walker et al.
Niraj Sharma:Catheter Ablation for Symptomatic Atrial Fibrillation a randomized, double blind, sham controlled, multicenter trial published in The Lancet in August 2026. The question was whether ablation improved AF specific quality of life more than a credible sham procedure. At nine German and Polish centers, two sixty two patients were randomized: one hundred and seventy three to ablation and eighty nine to sham. Median age was 67, about half were women, and paroxysmal and persistent AF were almost equally represented. Mean ejection fraction was approximately 60%.
Niraj Sharma:Values below 35% were excluded. Most ablations used radiofrequency or cryoballoon energy. Only five percent used pulsed field energy. The sham involved deep sedation and femoral venous sheaths, but no intracardiac catheter or transseptal puncture. Cardioversion was available when needed.
Niraj Sharma:Patients and follow-up teams were blinded, but operators weren't. The primary endpoint was six month change in the atrial fibrillation effect on quality of life questionnaire Higher scores mean less disability. Its summary score excludes the treatment satisfaction questions. The intention to treat analysis retained all randomized patients with missing data imputed and deaths assigned the worst possible change. Mean scores rose from 61.3 to 81.1 after ablation, and from 59.2 to 74.9 after sham, but the prespecified primary estimate wasn't the simple difference between those means.
Niraj Sharma:The rank based estimate was 2.6 points, with a 95% confidence interval from -2.7 to 8.0. The p value was 0.36. Superiority wasn't demonstrated. Equivalence wasn't demonstrated either. A pre specified mixed model sensitivity analysis accounting for sex and center estimated a 5.4 advantage, with a confidence interval from 1.0 to 9.8.
Niraj Sharma:That favorable result deserves attention, but doesn't replace the negative confirmatory analysis. Rhythm outcomes also need separating. Clinically detected recurrence was thirteen versus nineteen percent, with a hazard ratio of 0.66. Its confidence interval crossed one. During the seven day Holter at six months, mean AF burden was eleven point six versus twenty three point six percent.
Niraj Sharma:A post hoc combination of clinical and Holter detection found recurrence in twenty seven versus forty eight percent. That's not continuous monitoring of the entire follow-up period. Six ablation patients and four sham patients had serious events considered procedure related or possibly related. One patient died in each group, neither death attributed to the procedure. An ischemic stroke occurred in the sham group.
Niraj Sharma:Only about twenty two percent of invited patients enrolled. Baseline burden wasn't measured, follow-up was short, and the groups had a sex imbalance. Secondary and subgroup findings weren't adjusted for multiple comparisons. These limitations matter, but don't justify explaining away the primary result. Now to the beta blocker question because it's clinically important and easy to overstate.
Niraj Sharma:At baseline, a history of beta blocker therapy was reported in eighty eight percent of ablation patients and eighty nine percent of sham patients. The paper states that most patients continued to receive beta blockers during follow-up. The main report doesn't provide the detailed serial doses, indications, titration, adherence, or exercise heart rate responses needed to explain individual outcomes. Beta blockers are class II antiarrhythmic drugs. A trial reporting them separately from class I and class III rhythm control agents doesn't make their physiological effects disappear.
Niraj Sharma:Consider two possible situations: A patient with recurrent rapid AF may benefit from ventricular rate slowing. A patient spending more time in sinus rhythm after ablation may have less need for that rate control while still experiencing bradycardia, fatigue, hypotension, or a blunted heart rate response during exercise. Similar prescribing percentages therefore don't necessarily mean similar functional effects. But that's a plausible interaction, not a demonstrated explanation of this trial. Beta blocker withdrawal wasn't randomized.
Niraj Sharma:We can't claim that stopping treatment would have converted the primary endpoint into a positive result. Nor should we assume continuation was inappropriate. Heart failure, angina, and other indications may remain. The practical EP EDGE take is to reassess medications when rhythm changes. Review the original indication, resting and exertional rate, blood pressure and concomitant atrioventricular nodal blockers.
Niraj Sharma:Consider clinician guided adjustment when appropriate, not automatic withdrawal or abrupt discontinuation. Likewise, delayed recovery from advanced AF mediated cardiomyopathy isn't an established explanation here. This was largely a preserved ejection fraction population. Cardioversion, follow-up, medication changes, expectations, and natural symptom fluctuation could all contribute to improvement in the sham group. The trial cannot separate their individual contributions.
Niraj Sharma:Importantly, the earlier sham trials also used cardioversion. Patient selection isn't a complete explanation either. In an exploratory subgroup starting with AFEX scores below 50, both groups still improve substantially. The result asks us to improve symptom attribution and study the whole treatment pathway. A future trial could combine standardized rhythm guided medication titration, drug specific dosing records, exercise testing, and symptom rhythm correlation.
Niraj Sharma:That's how to test the beta blocker hypothesis rather than promote it into a conclusion. We've discussed PFA-SHAM and SHAM PVI in earlier EP EDGE Journal Watch issues. Rather than repeat those reviews, let's ask how their findings fit with the PVI SHAM AF result. Pavel Ozmancic et al. Pulsed field ablation versus SHAM to treat atrial fibrillation, the PFA-SHAM randomized clinical trial appeared in circulation in June 2026.
Niraj Sharma:Sixty highly symptomatic patients were randomized, with implantable monitoring and both recurrence and effect improvement as co primary endpoints. Recurrence occurred in two of thirty ablation patients versus twenty five of thirty sham patients. Affect improved by 43.9 versus 11.3 points. The estimated additional improvement was 32.6 points, with a 95% Bayesian credible interval from 20.2 to 44.9. Both co primary endpoints met superiority criteria.
Niraj Sharma:Rajdip Dulse and colleagues pulmonary vein isolation versus sham intervention in symptomatic atrial fibrillation. The SHAM PVI randomized clinical trial appeared online in JAMA in September 2024. Among one hundred and twenty six patients, cryoballoon isolation reduced continuously measured burden more than sham. Mean absolute reductions were 60.31 versus 35 percentage points. The secondary AFIC comparison favored ablation by 18.39 points, with a 95% confidence interval from 11.48 to 25.30, without multiplicity adjustment.
Niraj Sharma:So both earlier trials found rhythm improvement accompanied by additional patient reported benefit. The new trial also found lower sampled AF burden, but its primary quality of life comparison wasn't significant. That isn't a vote of two positive trials against one negative trial. Their primary questions differed: burden in sham PVI, recurrence in quality of life in PFA sham, and quality of life in PVI sham AF. Their populations differed too.
Niraj Sharma:Seventy seven percent of PFA sham patients had paroxysmal AF whereas seventy nine percent of sham PVI patients had persistent AF. The new trial was nearly evenly divided. Neither a simple paroxysmal versus persistent explanation nor a ranking of ablation energies follows from these comparisons. The earlier evidence remains evidence of benefit beyond sham. The new evidence limits how confidently we can promise the same incremental symptom benefit across different patients and treatment pathways.
Niraj Sharma:Where then do the findings diverge? Start with the control group. In PVI-SHAM AF, the observed mean within patient effect improvement was 19 points after ablation and 15.6 after sham. The primary rank based estimate was 2.6 points, with a 95% confidence interval from -2.7 to eight. That interval includes no benefit and some potentially meaningful benefit.
Niraj Sharma:It doesn't establish equivalence. The favorable mixed model sensitivity analysis remains relevant but cannot replace the prespecified primary analysis. Patient selection may matter. PFA-SHAM required an AFEX score of 50 or lower at screening. The new trial didn't impose that threshold, and baseline scores averaged about 60.
Niraj Sharma:But more severe symptoms don't settle the disagreement. In its exploratory subgroup below 50, scores improved by 35.9 after ablation and 30.8 after sham. That's a hypothesis about selection, not a validated rule identifying responders. Cardioversion doesn't resolve the difference either. All three trials included cardioversion when needed, and all assessed their main outcomes at around six months.
Niraj Sharma:In SHAM-PVI, approximately seventy eight percent of both groups were cardioverted. The control pathways weren't identical but cardioversion and short follow-up weren't unique to the new study. Monitoring is another distinction. The earlier trials used implanted continuous monitoring. PVI SHAM-AF measured burden with a seven day Holter six months without baseline burden.
Niraj Sharma:Its burden estimate cannot be compared directly with months of continuous recordings. Better monitoring would improve rhythm assessment but wouldn't automatically change the quality of life result. The beta blocker issue we discussed belongs here as a possible treatment interaction, not a proven explanation. Similar prescribing rates don't guarantee similar functional effects when one group spends more time in sinus rhythm. Yet none of these trials randomized beta blocker withdrawal.
Niraj Sharma:Drug specific doses, indications, and exercise responses would be needed to test that explanation. Both earlier trials were small and blinding weakened over time. Five PFA sham patients crossed over before six months. No sham PVI patients crossed over during randomized follow-up. These differences matter, without proving why the results diverged.
Niraj Sharma:The EPH interpretation is that improvement within a sham arm isn't synonymous synonymous with pure placebo. Cardioversion, medication, clinical attention, expectations and natural fluctuation may all contribute. What randomization estimates is the additional benefit of the assigned ablation strategy within each trial's care pathway. So why did PVI ShamAF miss its primary quality of life endpoint while PFA Sham and ShamPVI found additional benefit? Several differences could contribute, but none has been proved to explain the disagreement.
Niraj Sharma:Start with the patients. PVI had no minimum effect impairment threshold. Average scores were around 60 out of 100. Sham required 50 or lower at screening. Sham PVI started around 52.
Niraj Sharma:More impaired patients have more room to improve. That's the ceiling effect argument. And it's plausible. But 60 isn't symptom free. In the newer trials subgroup below 50, both ablation and sham patients still improve substantially.
Niraj Sharma:Baseline severity alone doesn't settle it. Now consider the medication. A history of beta blocker therapy was reported in almost ninety percent of both PVI-SHAM-AF groups. Most continued beta blockers during follow-up. Could a beta blocker help control rapid AF in one patient?
Niraj Sharma:And after sinus rhythm returns, could that same drug contribute to fatigue or blunt the heart rate response to exercise? Yes, that's plausible. The rhythm improves. But the patient may still feel limited. The earlier trials had more prescriptive class I and III drug withdrawal rules.
Niraj Sharma:That isn't the same as withdrawing beta blockers. Prior beta blocker exposure was also high in the positive sham PVI trial, so medication could modify the benefit. We don't know that it masked it. Withdrawal wasn't randomized and we lacked the detailed doses and functional responses needed to establish that explanation. Then, look at the sham group itself.
Niraj Sharma:Its average effect improvement was 15.6 points compared with 19 points after ablation. The observed improvements were much closer together. These patients weren't simply left untreated. Cardioversion when needed, medication management, and structured follow-up were part of the pathway. Expectations and natural symptom fluctuation may also contribute.
Niraj Sharma:But cardioversion was used in both earlier trials too. Active care wasn't unique to the newer study. We can't identify which component produced its larger sham response. Who agreed to participate also matters. Almost eighty percent of eligible patients approached declined.
Niraj Sharma:Perhaps those with disabling symptoms were less willing to risk sham treatment. That's a reasonable concern. But their symptom profiles weren't adequately recorded. We can't conclude that the most symptomatic patients disproportionately stayed away. Finally, how closely was rhythm measured?
Niraj Sharma:The earlier trials used continuous implanted monitoring. PVI assessed burden with a seven day Holter at six months without baseline burden. That gives a less complete picture of rhythm change and its relationship to symptoms. Continuous monitoring improves ascertainment. It doesn't guarantee perfect detection, and its absence cannot by itself explain a negative quality of life endpoint.
Niraj Sharma:What does this mean for success? Not that ablation has no value. Not that a better rhythm guarantees a better life. The trial didn't demonstrate superiority. It didn't establish equivalence either.
Niraj Sharma:Here's the EP Edge proposal for symptom directed ablation: The patient should achieve meaningful sustained improvement in the symptoms and activities that matter to them. Medication burden, repeat treatment and risk must also be acceptable. Report objective rhythm control separately. A brief recurrence needn't erase meaningful benefit. A quiet monitor doesn't explain persistent fatigue.
Niraj Sharma:We need prospective validation of how these outcomes fit together, not a new definition chosen after the results. The question isn't only did the AF return, it's also did life improve and what treatment did that improvement require. Now, let's change the intervention. Not another lesion, a structured exercise program. Bjarnaness et al.
Niraj Sharma:Presented NEXAF at the August twenty twenty six Congress. Their protocol appeared in Open Heart in March 2025. Its title is Effects of one Year Exercise in Patients with Atrial Fibrillation Study Protocol for the Norwegian Exercise in Atrial Fibrillation randomized controlled trial. The distinction matters. We have the published protocol and Congress results, not a full results manuscript in this source set.
Niraj Sharma:Two ninety five previously inactive patients were randomized at three Norwegian centers. Everyone received an implanted rhythm monitor. The exercise group had eight early supervised sessions, followed by home exercise, remote monitoring and coaching. Controls received usual care. This wasn't simply advice to exercise more.
Niraj Sharma:There was a program and there was follow through. The protocol targeted one hundred and fifty-three hundred minutes of moderate activity weekly. The vigorous activity target was seventy five-one hundred and fifty minutes. Those were prescribed targets, not measurements of what everyone actually achieved. At one year, AF occupied 3.9% of monitored time with exercise versus 7.1% with usual care.
Niraj Sharma:That's a 45% relative reduction, or 3.2 percentage points in absolute terms. The p value was 0.016. But did patients report greater improvement? Not on the quality of life co primary endpoint. Affect improved by 5.6 versus 4.4 points.
Niraj Sharma:The p value was 0.43. Fitness improved and investigators reported fewer hospitalizations. The available reports don't provide the absolute hospitalization counts or confidence intervals. Detailed adherence, medication changes, and adverse event data also need fuller reporting, so lower burden and better fitness without demonstrated additional AFEC benefit. Both findings belong in the conclusion.
Niraj Sharma:The EP EDGE take is to give structured exercise a practical place in AF care, a defined program, tailored goals and support, not a substitute for indicated rhythm treatment, and not a promise that every patient's symptoms will improve. The next questions are implementation questions: Who benefits most? What exercise dose is sustainable? And do the benefits last beyond the supervised study? Let's return to ablation with a more selective question, not Should everyone receive more lesions?
Niraj Sharma:Rather, Can we identify patients who benefit from treating a specific substrate? Astrid Paul Norden et al. Addressed this in low voltage ablation in persistent atrial fibrillation, the IDEAL AF randomized clinical trial. It appeared in JAMA in August 2026. At five Swedish centers, nine thirty six patients underwent voltage mapping.
Niraj Sharma:Only two zero nine had qualifying low voltage areas and were randomized. Median age was 72 and just over half were women. That selection is central. Only about one in five mapped patients qualified. The threshold was bipolar voltage below 0.5 mV over at least three square centimeters outside the isolation lines.
Niraj Sharma:Voltage information was concealed during pulmonary vein isolation, then revealed afterward. Additional radiofrequency ablation was tailored to the substrate, with block or isolation verified. The primary endpoint allowed one or two procedures with any repeat procedure performed within six months. Success meant no documented atrial arrhythmia at twelve months without rhythm control drugs. Beta blockers and rate controlling calcium channel blockers were exempt from withdrawal.
Niraj Sharma:What happened? Sixty nine of one hundred and two patients achieved the primary endpoint with additional substrate ablation. With isolation alone, forty of one hundred and seven did. That's sixty seven point six versus thirty seven point four percent. The absolute difference was 30.3 percentage points, with a 95% confidence interval from 17.4 to 43.2.
Niraj Sharma:The odds ratio was 3.5. That's an odds ratio, not a 3.5 fold increase in the probability of success. Could repeat procedures explain the advantage? Single procedure outcomes also favored additional ablation: sixty two point seven versus thirty one point eight percent. Quality of life improved more too.
Niraj Sharma:Serious adverse events occurred in ten versus eight patients. A control patient died after a possibly procedure related stroke. The trial doesn't establish safety equivalence, and monitoring was intermittent. The proportion of positive recordings isn't the same as continuously measured time in AF. Peter Kistler and David Chieng discussed the findings in their accompanying editorial, Beyond the Pulmonary Veins in Are We There Yet?
Niraj Sharma:Also published in August 2026, it emphasizes mapping quality and the risks of extensive or incomplete lesions. The EP edge take is selective treatment, not routine additional ablation. Identify the substrate carefully, verify the electrical endpoint, and remember this was radiofrequency evidence. Can pulsed field ablation reproduce the result? We don't know yet.
Niraj Sharma:Longer follow-up and replication with other platforms are needed. That question about success carries straight into FlexPulse. Ayman Hussain and colleagues reported Safety and effectiveness of a novel dual energy radiofrequency and pulse field ablation catheter: twelve month results of the FlexPulse study. It appeared in Europace in August 2026. The idea is flexibility: one focal catheter with a choice of radiofrequency or pulsed field energy.
Niraj Sharma:But does that flexibility translate into better outcomes? This manufacturer sponsored study wasn't designed to answer the comparative question. It was prospective and single arm. 24 centers treated one hundred and eighty patients with symptomatic drug refractory paroxysmal AF. Pulsed field energy was required on the posterior left atrium.
Niraj Sharma:Radiofrequency was required near coronary arteries. Additional ablation beyond the pulmonary veins occurred in about thirty seven percent. All patients achieved acute isolation. At twelve months, composite effectiveness was seventy four point six percent. The ninety five percent confidence interval ran from sixty seven point five to eighty point four percent.
Niraj Sharma:Failure included recurrence, specified repeat procedures, rhythm drug escalation, or cardioversion. Now here's the revealing comparison: Freedom from documented recurrence was seventy seven point four percent with the full monitoring protocol. Exclude the weekly telephone transmitted recordings and it became ninety two point six percent. Same patients, same procedures, different detection rules. That doesn't make the higher number false.
Niraj Sharma:It makes the monitoring definition essential. What about safety? Four primary safety events occurred in three of one hundred and eighty one safety evaluable patients, or one point seven percent. The events included pericardial effusion and pelvic hematoma. One patient developed transient ST elevation and posterior reversible encephalopathy syndrome.
Niraj Sharma:The report includes a day 15 hematoma despite specifying a seven day primary safety window. That detail needs clarification. At repeat procedures after blanking, 47 of 59 veins remained isolated (that's about eighty percent ), but only among patients returning for another procedure. It isn't a whole cohort durability estimate. A retrospective analysis of eighty three patients also examined lesion delivery.
Niraj Sharma:High adherence required two targets: at least eighty percent of lesions reached a pulsed field ablation index of 30, at least ninety percent met a six millimeters spacing target. Freedom from recurrence was eighty four point six versus seventy seven point two percent with lower adherence. The index wasn't available to operators during the trial. This is an association to test prospectively, not proof that using the index improves outcomes. And the average effect improvement of 31.6 points?
Niraj Sharma:Encouraging, but there's no randomized comparator. The EP edge take: a feasible dual energy strategy with useful procedural data, not evidence of superiority over another platform. The next step is prospective lesion guidance and controlled comparisons using comparable monitoring. Our final trial asks a difficult question: After intracranial hemorrhage, does anticoagulation improve the overall outcome for a patient with AF? This is ENRICH AF, presented by Ashkan Shomanesh at the August twenty twenty six European Cardiology Society Congress.
Niraj Sharma:Nine forty eight patients were randomized. Nine forty four were included in the reported analysis. Mean age was 77. Treatment was open label with blinded endpoint assessment. Edoxaban was given at sixty mg daily, reduced to thirty when indicated.
Niraj Sharma:The comparator was avoiding anticoagulation. About half the controls received an antiplatelet agent. After an average twenty eight months, stroke or systemic embolism occurred in eleven point eight versus twelve point eight percent. The hazard ratio was 0.88. Its 95% confidence interval ran from 0.61 to 1.26.
Niraj Sharma:The p value was 0.48. So no demonstrated superiority on the primary endpoint. But don't stop there. Ischemic stroke occurred in six point two percent with edoxaban versus ten point three percent with control. Hemorrhagic stroke moved the other way: five point eight percent versus one point nine percent.
Niraj Sharma:The ischemic stroke hazard ratio was zero point five seven. For hemorrhagic stroke, it was two point nine nine. Major bleeding occurred in eleven point six versus five point two percent. Fatal bleeding occurred in four point one versus zero point eight percent. This isn't a drug doing nothing it's protection against one type of event accompanied by harm from another.
Niraj Sharma:And we can't simply subtract every event percentage to create a net benefit score. Outcomes can overlap and their consequences differ. Hemorrhage subtype matters too. The reported subgroup findings are hypothesis generating, not validated prescribing rules. The official Congress report also describes a safety related halt to enrollment in two subgroups: lobar intraparenchymal hemorrhage and convexity subarachnoid hemorrhage.
Niraj Sharma:The EP EDGE take: These findings don't support routine edoxaban in an unselected posthemorrhage population. Decisions need the patient's specific ischemic and bleeding risks discussed with stroke neurology and the patient. What about another anticoagulant or appendage occlusion? This trial doesn't establish either as superior. Those strategies need their own evidence and the fuller ENRICH AF report remains important for understanding who might benefit and who might be harmed.
Niraj Sharma:We'll await its publication. Before we finish, let's bring the issue together. PVI sham AF found lower sample rhythm burden without superiority on its primary quality of life analysis. Beta blockers deserve reassessment and study, not blame assigned after the result. The earlier PFA-SHAM and SHAM-PVI trials showed additional rhythm and patient reported benefit in their populations.
Niraj Sharma:The disagreement asked us to examine selection, measurement and the whole treatment pathway, not declare that one trial cancels the others. Natali's review, Marouche and Glotz's editorial, and Dulse's substudy bring us back to the same question: What are we calling success? Recurrence, burden, symptoms, and treatment exposure should be measured separately, then interpreted together. FlexPulse shows a feasible dual energy strategy. It also shows how much monitoring can change the apparent success rate.
Niraj Sharma:NEXAF supports structured exercise for reducing burden and improving fitness. It didn't demonstrate additional benefit on its quality of life co primary endpoint. IDEAL AF supports targeted substrate ablation in selected patients. Kistler and Ching remind us that careful mapping and verified endpoints matter. An ENRICH AF, less ischemic stroke but more hemorrhagic stroke and bleeding.
Niraj Sharma:The components matter as much as the composite. Different interventions. One recurring lesson: Be clear about the outcome you are trying to improve and measure whether that improvement matters to the patient. You'll find the full discussion, graphics and references in EP Edge Journal Watch on LinkedIn and at epedge.substack.com. Please share the newsletter and podcast with colleagues who would find them useful.
Niraj Sharma:Questions, suggestions, or concerns can be emailed to epedge. Castgmail . com. Thank you for listening. Take care and bye for now.