EP Edge Journal Watch: Cardiac Electrophysiology Research

EP Edge® Journal Watch | Issue 40 | October 2026

Beyond AF Burden: Stroke Risk, Rhythm Progression, Atrial Pacing, and Sudden Death Prevention

Should oral anticoagulation continue after successful atrial fibrillation ablation? Does AF density provide better stroke-risk information than conventional burden measurements? Can the GLORIA-AF score improve thromboembolic risk prediction? And could autonomic modulation or advances in pacing and defibrillator therapy change electrophysiology practice?

In Issue 40 of EP Edge® Journal Watch, Dr. Sharma examines eleven research papers, with detailed analysis of five major studies and concise reviews of six additional publications.

The episode explores study methodology, statistical interpretation, clinical relevance, and the distinction between promising associations and evidence sufficient to change practice.

Featured Studies

1. Anticoagulation After AF Ablation | Ren et al.

A prospective observational analysis of 13,669 patients examines continuation versus discontinuation of oral anticoagulation following catheter ablation.

Continued anticoagulation after six months was not associated with a statistically significant reduction in thromboembolism across stroke-risk categories, while major bleeding was higher in anticoagulated high-risk patients. The interpretation is complicated by nonrandom treatment selection, differences in baseline stroke risk, and incomplete quantitative AF burden assessment.

We discuss adjusted hazard ratios, absolute event rates, confidence intervals, confounding by indication, and the implications of contemporary randomized evidence, including ALONE-AF, OCEAN, and OPTION.

The accompanying editorial by Alhassan and Kwaku provides additional context for individualized anticoagulation strategies after ablation.

Ren et al. DOI:
https://doi.org/10.1161/JAHA.125.047527

2. AF Density and Ischemic Stroke | Rosman et al.

Can the temporal clustering of atrial fibrillation episodes improve stroke prediction beyond total AF burden?

This observational study of 12,868 patients with implanted cardiac monitors evaluates AF density, a measure of how concentrated or dispersed arrhythmia episodes are over time.

Higher AF density was associated with greater modeled ischemic stroke risk, even when cumulative AF burden was considered.

We examine the parametric g-formula, adjustment for time-varying covariates, competing risks, and why a prognostic association does not establish a treatment threshold for anticoagulation.

Rosman et al. DOI:
https://doi.org/10.1093/eurheartj/ehag203

3. GLORIA-AF Stroke Weighted Risk Score | Xie et al.

A new weighted stroke-risk score incorporating ten routinely available clinical variables is developed in 20,517 patients and externally validated in 8,309 patients from European and Asia-Pacific AF registries.

The score demonstrated statistically better stroke discrimination than CHA₂DS₂-VA, with external validation C-index values of 0.652 versus 0.616.

We examine discrimination, calibration, integrated discrimination improvement, net reclassification improvement, and decision-curve analysis.

A central question is whether better statistical prediction produces sufficiently meaningful improvement to influence anticoagulation decisions, particularly when many patients in the derivation cohort were already anticoagulated.

Xie et al. DOI:
https://doi.org/10.1093/europace/euag236

4. Stellate Ganglion Block and Postoperative AF | Tian et al.

A randomized controlled trial evaluates preemptive ultrasound-guided left stellate ganglion block in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Among 108 patients in the modified intention-to-treat analysis, postoperative AF occurred in 18.5% of the intervention group versus 44.4% of controls.

We examine the absolute risk reduction, odds ratio, exploratory number needed to treat, perioperative beta-blocker use, incomplete inclusion of randomized participants, absence of a sham procedure, and limitations of short-term follow-up.

The study raises important questions about autonomic modulation as a preventive strategy, but larger multicenter trials are required before routine clinical adoption.

Tian et al. DOI:
https://doi.org/10.1016/j.jacep.2026.07.006

5. ICD Therapy in Hypertrophic Cardiomyopathy | Rowin et al.

An international study from 25 centers examines long-term implantable cardioverter-defibrillator outcomes in 3,387 patients with hypertrophic cardiomyopathy.

Appropriate device therapy occurred in 16% of patients overall, including 15% of primary-prevention recipients.

Among primary-prevention patients who experienced appropriate device therapy, 16% received their first intervention at least ten years after implantation.

We explore appropriate device interventions, late ventricular arrhythmias, clinical risk markers, sudden cardiac death, and the distinction between an appropriate ICD intervention and a death that would certainly have occurred without treatment.

The study provides valuable evidence about long-term device performance and the continued importance of individualized sudden-death risk assessment.

Rowin et al. DOI:
https://doi.org/10.1161/CIRCULATIONAHA.125.078597

Additional Research Covered

6. Device-Detected Atrial High-Rate Episodes | Botto et al.

Does a daily atrial high-rate episode burden of at least six minutes identify patients at increased risk of cardiovascular death, worsening heart failure hospitalization, or stroke?

This post hoc analysis of 1,160 patients from the B3 randomized pacing trial found a strong association with composite cardiovascular outcomes among patients without previously diagnosed AF.

The association was driven mainly by worsening heart failure hospitalization and cardiovascular death, rather than a statistically significant increase in stroke or transient ischemic attack.

The results emphasize the broader prognostic implications of device-detected atrial arrhythmias while highlighting the limitations of observational subgroup analyses.

Botto et al. DOI:
https://doi.org/10.1016/j.hrthm.2026.02.048

7. Progression of Persistent AF | Thakur et al.

A systematic review and meta-analysis evaluates progression from persistent to permanent atrial fibrillation, reporting a pooled progression rate of 16.42 per 100 person-years.

Substantial between-study heterogeneity and differences in the definition of permanent AF complicate interpretation.

The analysis also explores whether greater exposure to pulmonary vein isolation is associated with lower progression rates, while emphasizing that study-level associations do not establish causal treatment effects.

Thakur et al. DOI:
https://doi.org/10.1016/j.hrthm.2026.04.012

8. Predictors of Recurrence After AF Ablation | Chan et al.

Should we add posterior wall isolation during pulsed field ablation for persistent atrial fibrillation? How durable are pulmonary vein isolation and additional atrial lines? Can a defibrillation lead placed in the left bundle branch area provide reliable early performance while simplifying device therapy?

Join Dr. Sharma for EP Edge® Journal Watch Issue 39, October 2026. We examine four papers in depth: PIFPAF-PFA, pulmonary vein isolation durability across pulsed field systems, invasive remapping of atrial lesion sets with a dual-energy lattice-tip catheter, and the LEADR LBBAP defibrillation lead study. We then give brief takeaways from twenty additional articles spanning AF ablation safety, conduction system pacing and cardiac resynchronization therapy, anticoagulation, metabolic therapies, AF progression and burden, cardioversion, cardiac arrest, ventricular arrhythmias, congenital long QT syndrome, and lead extraction.

Our aim is to connect clinically relevant findings with the methods and uncertainty behind them. We distinguish acute procedural success from chronic durability, electrical surrogates from patient outcomes, and randomized evidence from selected observational comparisons. We explain effect estimates, denominators, confidence intervals, and why a nonsignificant result does not establish equivalence. Accompanying editorials and the pacing viewpoint are integrated into the relevant discussions rather than counted as additional articles.

The newsletter contains detailed analyses of all 24 articles. The episode concentrates its extended analysis on the four featured papers below; the other twenty receive concise spoken takeaways. Article numbers retain the revised newsletter numbering, and entries follow newsletter order within each coverage section.

FOUR PAPERS COVERED IN DEPTH

1. Pulmonary Vein Isolation Using Pulsed Field Ablation With vs Without Posterior Wall Isolation in Patients With Symptomatic Persistent Atrial Fibrillation: The PIFPAF-PFA Randomized Clinical Trial

Roten L, Maurhofer J, Krisai P, et al. | JAMA | August 2026

Roten and colleagues ask whether empirical posterior wall isolation adds benefit to PFA-based PVI at first ablation for symptomatic persistent AF. In 206 randomized patients with continuous implantable-monitor surveillance, one-year Kaplan-Meier atrial tachyarrhythmia recurrence estimates were 50.6% with posterior wall isolation versus 60.6% with PVI alone. The primary result did not establish superiority: rate ratio 0.75, 95% CI 0.51–1.09, P=.13.

Mean arrhythmia burden was 6.9% versus 11.0%, and episodes lasting at least one day occurred in 10 versus 25 patients. These secondary signals require confirmation because multiple comparisons were not corrected, and most secondary endpoints were nonsignificant. Repeat intervention, drug use, and quality-of-life comparisons did not establish an advantage. We integrate Kistler and Chieng’s editorial on empirical anatomical ablation versus targeting demonstrated substrate, while avoiding cross-trial claims of superiority. Routine additional posterior wall isolation remains unproven in this setting; limited power also prevents a conclusion of equivalence.

DOI: 10.1001/jama.2026.17598

2. Durability of pulmonary vein isolation: Does the pulsed field ablation system matter?

Kakarla S, Iwakawa H, Ariyaratnam JP, et al. | Heart Rhythm | October 2026

Kakarla and colleagues compare pentaspline and balloon-in-basket PFA in a retrospective two-center cohort of 132 index procedures. Clinical recurrence was 10.5% versus 19.6% (P=.12), and 34 propensity-matched clinical pairs had six versus seven recurrences. The notable durability signal came from only 17 selected patients returning for repeat ablation: reconnection affected 9/32 versus 1/35 veins, and all veins remained isolated in 3/8 versus 8/9 patients.

We examine why these findings cannot establish platform superiority. Matching of the clinical cohort did not randomize or make the separate redo sample representative. Veins within patients are correlated, monitoring intensity differed, and posterior wall treatment was uneven. Acute isolation, selected invasive remapping, and clinical recurrence answer different questions. The study supports prospective comparison with systematic remapping and standardized surveillance, while emphasizing mapping of the actual recurrence mechanism at redo.

DOI: 10.1016/j.hrthm.2026.05.018

5. Durability of atrial linear lesion sets using a dual-energy lattice-tip catheter: Data from invasive remapping

Nies M, Benesch Vidal ML, My I, et al. | Heart Rhythm | October 2026

Nies and colleagues investigate whether acute atrial block persists after ablation with a dual-energy lattice-tip catheter. Only 39 of 252 treated patients underwent remapping, for recurrence or planned appendage occlusion. The 71 remapped lesion sets comprised 18 pulmonary vein encirclements and 53 additional lines. Durable block was present in 54/71 sets; separately, 31/36 individual veins remained isolated.

Roof lines, posterior boxes, and cavotricuspid lines remained blocked in 6/6, 10/10, and 7/7 cases, respectively. Anterior and mitral lines were durable in only 9/17 and 7/13. Small denominators, different remapping intervals, mixed energy strategies, and selected patients preclude controlled comparisons of energy or lesion location. We discuss the clinical consequences of gaps and macroreentry, the need to confirm bidirectional block when a line is indicated, and why visual continuity or promising remapping proportions do not establish better clinical outcomes.

DOI: 10.1016/j.hrthm.2026.05.004

9. Safety and performance of a novel defibrillation lead for left bundle branch area placement: Primary results of the LEADR LBBAP clinical trial

Vijayaraman P, Liu X, Denman R, et al. | Heart Rhythm | October 2026 issue

Vijayaraman and colleagues report early safety and performance of a novel ICD lead designed for left bundle branch area placement. This prospective single-arm study enrolled 323 patients; implantation succeeded in 293/307 attempts. All 162 patients completing protocol defibrillation testing met the acute efficacy endpoint, exceeding a historical performance benchmark. Mean follow-up was only 2.6 months. Pacing thresholds were low and stable, while five major lead-related complications required revision; estimated freedom from major lead-related complications was 97.9% at three months.

We distinguish implantation, testing, pacing, sensing, and complication denominators. Successful protocol testing does not guarantee future spontaneous-arrhythmia termination or chronic lead integrity. Approximately half received an additional LV lead, and left bundle area placement did not uniformly confirm conduction system capture. The study therefore does not establish that this lead alone replaces conventional CRT. Manufacturer sponsorship, incomplete testing, and short follow-up reinforce the need for independent long-term data on defibrillation, capture, sensing, mechanical reliability, and extraction. The October 2026 issue follows the paper’s 2025 online publication.

DOI: 10.1016/j.hrthm.2025.10.028

TWENTY ADDITIONAL ARTICLES WITH BRIEF PODCAST TAKEAWAYS

3. Dosing of single-shot pulsed field ablation systems: A systematic review of efficacy and safety balance

Bax IN, Bolhuis RE, van der Graaf M, ...

In this special EP Edge® Journal Watch Issue 38, recorded at HRX, with the Heart Rhythm Society Live 2026 in Atlanta, Dr. Niraj Sharma is joined by Dr. Michael Lloyd, Professor of Medicine at Emory University, for a focused discussion of three provocative studies with direct implications for contemporary cardiac electrophysiology.

First, they examine the emerging role of large language models and artificial intelligence in ECG interpretation. How accurately can off-the-shelf, zero-shot LLMs interpret electrocardiograms, and are currently available general-purpose AI models ready to participate in clinical ECG analysis?

The discussion then turns to ventricular tachycardia detected during everyday life by wearable devices. New data suggest that VT may be detected far more frequently in individuals using wearable monitoring than traditional estimates would suggest. Drs. Sharma and Lloyd discuss what these findings may mean for electrophysiologists increasingly confronted with rhythm data generated outside the clinic.

Finally, the episode explores the continuing evolution of conduction system pacing, with new data comparing left bundle branch area pacing (LBBAP) and deep septal pacing (DSP). The conversation examines differences in clinical outcomes, the reported mortality signal associated with deep septal pacing, and an important practical problem for the field: inconsistent agreement about what actually constitutes successful LBBAP versus deep septal pacing.

Recorded from HRX Live 2026, this episode goes beyond the abstracts to examine what the findings mean clinically, where the uncertainties remain, and how they may influence electrophysiology practice.

Topics discussed include:

• Artificial intelligence and zero-shot LLMs for ECG interpretation
• Accuracy and limitations of AI-assisted electrocardiogram analysis
• Wearable cardiac monitoring and real-world ventricular tachycardia detection
• Ventricular arrhythmias detected outside traditional clinical monitoring
• Left bundle branch area pacing (LBBAP)
• Deep septal pacing (DSP)
• Conduction system pacing definitions and adjudication
• Mortality and clinical outcomes with physiologic pacing strategies
• Emerging research and innovation from HRX Live 2026

EP Edge® Journal Watch provides clinically focused analysis of important new research in cardiac electrophysiology, emphasizing not simply what a study found, but how the evidence should be interpreted and what it may mean for clinical practice.

Hosted by Dr. Niraj Sharma
Special HRX discussion with Dr. Michael Lloyd, MD, FACC, FHRS

In EP Edge® Journal Watch Issue 37, September 2026, Dr. Sharma reviews 13 important studies in cardiac electrophysiology, with a focus on what the data actually mean for clinical practice. This episode goes beyond abstracts and headline results to examine why each study was performed, the clinical question investigators were trying to answer, the methodology used, the statistics behind the major findings, important limitations, and what the results may mean for electrophysiologists going forward.

This episode begins with a major theme in contemporary atrial fibrillation care: left atrial appendage occlusion and stroke prevention.

First, we examine the mechanistic study “Left Atrial Appendage Thrombosis in Patients With Atrial Fibrillation” from Ji Zhou and colleagues. Histologic examination of surgically removed appendages from LAAOS III participants identified microscopic thrombi in the trabecular crypts, raising important questions about persistent local thrombogenicity despite anticoagulation and providing biological context for why mechanical left atrial appendage exclusion may provide additional protection in selected patients.

We then turn to two important meta-analyses comparing left atrial appendage occlusion with medical therapy. The contemporary randomized evidence suggests that LAAO may substantially reduce nonprocedural bleeding, but the possibility of a modest increase in ischemic stroke remains unresolved. The discussion focuses on why LAAO should be viewed as a trade-off between procedural risk, long-term bleeding exposure, and stroke protection rather than simply as an equivalent replacement for direct oral anticoagulation.

The episode then examines the ADVANCE LAA study, led by Dhanunjaya Lakkireddy, evaluating Amulet implantation in patients who failed Watchman anatomical screening. Despite more challenging left atrial appendage anatomy, Amulet implantation remained highly successful, reinforcing an important practical concept: failure of one device geometry does not necessarily mean failure of the LAAO strategy.

Next, we review randomized evidence comparing direct oral anticoagulants versus dual antiplatelet therapy after left atrial appendage closure. The pooled data showed markedly lower device-related thrombus with DOAC-based therapy and, perhaps surprisingly, less major and minor bleeding than with DAPT. The clinical question is no longer simply whether anticoagulation can be stopped, but what antithrombotic strategy provides the safest bridge through the early device-healing period.

The second major theme is pulsed field ablation safety and lesion durability.

A major Circulation study led by Enrico Ferro compared neurological outcomes after pulsed field ablation and radiofrequency ablation. Although absolute stroke and TIA rates remained low, PFA was associated with a higher 30-day neurovascular event rate in this observational registry. Dr. Sharma discusses the difference between relative and absolute risk, why propensity adjustment cannot eliminate residual confounding, and why rapid adoption of PFA makes rigorous post-market safety surveillance essential.

We then examine “Transmurality and Autonomic Effects of Pulsed Field Ablation on the Mitral Isthmus” by Apoor Patel and colleagues. Using direct vein of Marshall recordings, investigators demonstrated that apparent endocardial mitral isthmus block frequently concealed persistent epicardial conduction. PFA alone achieved complete block in fewer than half of patients, while vein of Marshall ethanol infusion substantially increased block rates. The study also demonstrated that PFA generally spared local parasympathetic innervation, whereas ethanol infusion produced denervation. The findings raise important questions about how we define lesion completeness in the PFA era.

The episode then moves to atrial fibrillation detection and prediction.

The PAVA score, developed by Baptiste Maille and colleagues, attempts to identify patients at lower likelihood of AF detection after cryptogenic stroke using premature atrial contractions, age, significant valvular disease, and left atrial enlargement. The score performed well in internal validation but less strongly in external validation, highlighting why prediction models should be judged by more than their best AUC.

We also discuss the study “Wearable smartwatches for atrial fibrillation detection and burden estimation after ablation: comparison with continuous monitoring.” Using continuous implantable cardiac monitor data from CIRCA-DOSE, investigators simulated Apple Watch and Fitbit AF-detection algorithms. Smartwatch strategies detected substantially more recurrence than conventional short Holter monitoring, while wearable-estimated AF burden correlated closely with continuous monitoring. The episode examines the critical distinction between correlation and agreement, and why simulation is not the same as prospective real-world validation.

Another study evaluates the neutrophil-to-lymphocyte ratio as a predictor of postoperative atrial fibrillation after cardiac surgery. Elevated NLR was associated with postoperative AF, supporting an inflammatory component to arrhythmogenesis, but its standalone diagnostic performance was only moderate. This provides a useful example of why a statistically significant biomarker association does not automatically translate into a clinically useful prediction test.

Two practical ventricular arrhythmia studies then return the discussion to the 12-lead ECG.

Masafumi Sugawara and colleagues demonstrate that comparing the PVC QRS axis with the patient’s baseline sinus-rhythm axis may help distinguish true para-Hisian PVCs from RVOT and LVOT mimics. Rather than interpreting the ectopic beat in isolation, the study suggests that the patient’s baseline electrical orientation should become part of PVC localization.

Yoshihisa Naruse and colleagues introduce the V6R/V4R index, a simple ECG parameter designed to distinguish aortic cusp ventricular arrhythmias from non-cusp LVOT origins. The index may help determine where mapping should begin, although the paper contains inconsistencies in the reported diagnostic performance that deserve careful interpretation.

Finally, the episode explores whether SGLT2 inhibitors may reduce sudden cardiac death.

Andrea Matteucci and colleagues pooled adjudicated randomized evidence involving empagliflozin and dapagliflozin across nearly 59,000 participants. SGLT2 inhibition was associated with approximately an 18 percent reduction in the odds of sudden cardiac death, with consistent results across the included trials. The key unanswered question is mechanism. Does this reflect a direct antiarrhythmic effect, or is sudden death reduced indirectly through improvements in heart failure, myocardial energetics, fibrosis, renal function, and overall cardiovascular stability?

Throughout the episode, Dr. Sharma focuses on the difference between statistical significance and clinical significance, association versus prediction, relative versus absolute risk, and the practical implications of these studies for electrophysiology practice.

Topics include: atrial fibrillation, left atrial appendage occlusion, Watchman, Amulet, DOACs, DAPT, device-related thrombus, pulsed field ablation, PFA safety, stroke after AF ablation, mitral isthmus ablation, vein of Marshall ethanol infusion, wearable AF monitoring, Apple Watch, implantable loop recorders, cryptogenic stroke, PAVA score, postoperative atrial fibrillati...

What defines successful atrial fibrillation ablation: fewer recurrences, lower AF burden, better quality of life, or all three? In this ESC Congress 2026 special issue of EP Edge Journal Watch, Dr. Sharma examines evidence from Munich, Germany, August 28–31, 2026, alongside previously covered sham-controlled trials to explore what meaningful patient benefit should look like.

PVI-SHAM-AF leads the discussion. Rolf Wachter and colleagues found lower sampled atrial fibrillation burden after catheter ablation, but no demonstrated superiority over sham on the primary Atrial Fibrillation Effect on Quality-of-Life (AFEQT) endpoint. We examine the primary result, the favorable sensitivity analysis, and why failure to demonstrate superiority does not establish equivalence.

PFA-SHAM and SHAM-PVI provide the earlier evidence. These trials demonstrated additional patient-reported benefit with pulsed field ablation and cryoballoon pulmonary vein isolation, respectively. Their differing populations, endpoint priorities, and monitoring methods help frame the comparison, without implying that one ablation technology is superior to another.

Our In Depth synthesis examines baseline symptom severity, possible ceiling effects, recruitment, cardioversion, antiarrhythmic management, beta blockers, and continuous versus intermittent rhythm monitoring. These are potential contributors to the discordant findings, not established explanations. Drawing on Andrea Natale’s review, the Marrouche–Glotzer editorial, and Dulai’s SHAM-PVI substudy, we distinguish rhythm recurrence from residual burden, symptoms, functional improvement, and treatment burden. What should count as clinical success, and which definitions still need prospective validation?

FlexPulse follows with 12-month results for focal dual-energy radiofrequency and pulsed field ablation. We review 74.6% composite effectiveness, safety, redo-mapping findings, and the substantial effect of monitoring intensity on apparent success. Single-arm results and retrospective lesion-quality associations are not comparative proof.

NEXAF examines structured exercise in AF care. A supervised-to-home exercise program reduced continuously monitored AF burden by 45% relative to usual care, but did not demonstrate superiority on the quality-of-life co-primary endpoint.

IDEAL-AF evaluates individualized low-voltage substrate ablation in selected patients with persistent AF. We discuss improved rhythm outcomes beyond pulmonary vein isolation, patient selection, verified electrical endpoints, and the accompanying Kistler–Chieng editorial. The findings do not justify routine additional lesions in every patient.

ENRICH-AF closes with edoxaban after intracranial hemorrhage. Fewer ischemic strokes were accompanied by more hemorrhagic strokes and major bleeding, without demonstrated superiority on the primary stroke or systemic embolism endpoint.

NEXAF and ENRICH-AF are discussed as congress-results reports, not full results manuscripts. Designed for electrophysiologists, cardiologists, trainees, researchers, and cardiovascular care teams, this episode connects trial interpretation with patient counseling, medication review, and shared decision-making.

Explore the complete newsletter, infographics, and references, and follow EP Edge Journal Watch for weekly electrophysiology analysis.

In this special edition of EP Edge® Journal Watch, Dr. Sharma reviews the major breaking cardiovascular and electrophysiology science presented at the European Society of Cardiology Congress 2026 in Munich.

The episode begins with two important electrophysiology trials that challenge familiar clinical thresholds.

First is SINGLE-AF, led by Daehoon Kim and colleagues and published in the New England Journal of Medicine in August 2026. The trial provides the first randomized evidence evaluating direct oral anticoagulation versus no anticoagulation in patients with atrial fibrillation at intermediate stroke risk. Dr. Sharma explains why this population has remained a clinical gray zone, how the trial was designed, what the 69% relative reduction in the primary net clinical endpoint actually means, why the absolute event rate remains important, and whether these findings should change anticoagulation decisions in everyday AF practice.

Next is CMR GUIDE, led by Joseph B. Selvanayagam and colleagues and published in JAMA in August 2026. This provocative randomized trial tested whether myocardial scar identified by late gadolinium enhancement cardiac MRI could help identify patients with LVEF 36% to 50% who may benefit from a primary-prevention ICD. Although the primary endpoint was neutral, the reduction in sudden cardiac death and the striking signal among patients younger than 70 years raise a much larger question for electrophysiologists: Is LVEF alone still an adequate way to determine sudden cardiac death risk and ICD candidacy?

The episode then moves into a rapid review of additional major developments from ESC 2026.

The 2026 ESC Heart Failure Guidelines, led by Lars Køber, Marianna Adamo and colleagues and published in the European Heart Journal, eliminate the traditional HFmrEF category, redefine HFrEF as LVEF below 50%, introduce a Stage A through D heart failure framework, and reorganize therapy into foundational, additional, and guideline-directed interventional treatment. Dr. Sharma discusses why this major change in heart failure classification does not automatically change ICD or CRT indications, but may influence how future device therapy is studied.

The Fifth Universal Definition of Myocardial Infarction, led by Nicholas Mills, L. Kristin Newby, Sarah Zaman and colleagues, introduces a simpler pathophysiologic classification of primary MI, secondary MI, and procedure-related MI. Of particular relevance to electrophysiology, the new framework may help clarify how elevated troponin should be interpreted in patients with rapid atrial fibrillation and other tachyarrhythmias, separating true ischemic myocardial infarction from acute myocardial injury.

Also discussed is the major Nature Reviews Cardiology review led by Thomas Münzel and colleagues examining nicotine and cardiovascular disease. The review places combustible cigarettes, heated tobacco products, e-cigarettes, and oral nicotine products along a continuum of cardiovascular harm and emphasizes that reduced exposure to combustion does not make nicotine-containing products cardiovascularly neutral.

Finally, Dr. Sharma examines an innovative study presented by Viana Copeland and colleagues using artificial intelligence to analyze nearly 100,000 mammograms for cardiovascular signals associated with hypertension, ischemic heart disease, and stroke. The concept raises the intriguing possibility that imaging obtained for one clinical purpose may ultimately provide useful information about entirely different disease phenotypes.

Throughout the episode, the emphasis is not simply on reporting trial results. Dr. Sharma explains why each study was needed, how it was designed, what the statistics actually mean, what the limitations are, and how the findings may influence clinical electrophysiology practice.

Topics include:

•  ESC Congress 2026 Munich 
•  SINGLE-AF trial 
•  atrial fibrillation and anticoagulation 
•  CHA₂DS₂-VA and intermediate stroke risk 
•  DOAC therapy 
•  CMR GUIDE trial 
•  cardiac MRI and late gadolinium enhancement 
•  myocardial scar and sudden cardiac death 
•  primary-prevention ICD therapy 
•  LVEF greater than 35% 
•  2026 ESC Heart Failure Guidelines 
•  HFrEF and HFpEF 
•  Fifth Universal Definition of Myocardial Infarction 
•  Type 2 MI and tachyarrhythmias 
•  nicotine and cardiovascular disease 
•  vaping and cardiovascular risk 
•  artificial intelligence in cardiovascular imaging 
•  AI mammography and cardiovascular screening 
•  cardiac electrophysiology 
•  sudden cardiac death risk stratification 

For the full statistical analysis, references, figures, and graphics, read EP Edge® Journal Watch on LinkedIn and Substack at epedge.substack.com.

Questions, suggestions, or concerns: [email protected].

In this EP Edge and Heart Rhythm Society collaborative podcast, Dr. Niraj Sharma and Dr. Mike Lloyd examine new evidence challenging several long-standing assumptions in cardiac electrophysiology: when to choose catheter ablation over antiarrhythmic drug therapy for atrial fibrillation, whether left bundle branch area pacing should replace conventional right ventricular pacing in patients who require substantial ventricular pacing, and how broadly the lessons of CAST should continue to restrict flecainide and other Class Ic antiarrhythmic drugs.

The atrial fibrillation discussion brings together two complementary 2026 Heart Rhythm meta-analyses. Demy L. Idema and colleagues evaluated antiarrhythmic drugs versus catheter ablation for rhythm control across randomized controlled trials, focusing on AF recurrence, hospitalization, mortality, and treatment-related complications. Marwan Shawki and colleagues examined the safety of catheter ablation versus antiarrhythmic drugs across 24 randomized trials involving 6,665 participants. Together, the studies raise an important contemporary question: as ablation becomes more effective and procedural safety improves, does antiarrhythmic drug therapy still deserve an automatic position ahead of ablation in the AF treatment pathway?

The discussion then turns to physiologic pacing and the PACE-HF trial by Jenish P. Shroff and colleagues, published in the European Heart Journal. In this prospective randomized trial, left bundle branch area pacing was compared with conventional right ventricular pacing in patients with preserved or mildly reduced left ventricular ejection fraction who were expected to require substantial ventricular pacing. The trial provides randomized evidence on ventricular function, pacing burden, heart failure hospitalization, and the potential consequences of chronic nonphysiologic right ventricular activation.

Finally, the podcast revisits flecainide more than three decades after the Cardiac Arrhythmia Suppression Trial (CAST). The discussion incorporates the systematic review by Li and colleagues in Heart Rhythm examining how CAST reshaped flecainide research and clinical use, together with the nationwide cohort study by T.-C. Huang and colleagues in Heart Rhythm evaluating Class Ic antiarrhythmic therapy after PCI in patients with new-onset atrial fibrillation. The central question is not whether CAST was correct in the post-myocardial-infarction population it studied, but whether its findings have been extrapolated too broadly to contemporary patients with stable or revascularized coronary disease, preserved ventricular function, and atrial rather than ventricular arrhythmias.

Across atrial fibrillation ablation, conduction-system pacing, and Class Ic antiarrhythmic therapy, the episode asks a common question: when new evidence challenges an established electrophysiology default, when is the evidence strong enough to change everyday practice?

Studies Discussed

Idema DL, et al. Antiarrhythmic drugs vs catheter ablation as rhythm control for atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials. Heart Rhythm. 2026;23:1465-1475.

Shawki M, et al. Safety of catheter ablation compared with antiarrhythmic drugs for atrial fibrillation: A systematic review and meta-analysis of randomized trials. Heart Rhythm. 2026;23:1453-1464.

Shroff JP, et al. Left bundle branch area pacing vs right ventricular pacing in preserved or mildly reduced ejection fraction: the PACE-HF trial. European Heart Journal. 2026;47:3298-3300.

Li et al. Flecainide use before and after the Cardiac Arrhythmia Suppression Trial: A systematic review. Heart Rhythm. 2026.

Huang TC, et al. Class Ic antiarrhythmic therapy after PCI in new-onset atrial fibrillation: Safety and clinical outcomes from a nationwide cohort. Heart Rhythm. 2026;23:e1372-e1382.

What can nine carefully selected studies teach us about the changing practice of cardiac electrophysiology?

In EP Edge® Journal Watch Issue 34, August 2026, Dr. Sharma provides a clinically focused review of emerging evidence across atrial fibrillation, pulsed field ablation, implantable cardiac devices, sudden death prevention, resuscitation, occupational radiation safety, and postural orthostatic tachycardia syndrome.

This episode examines whether transvenous and subcutaneous ICD shocks produce different patterns of myocardial injury; the incidence and clinical meaning of migraine following pulsed field ablation; whether routine mechanical CPR improves meaningful survival after out-of-hospital cardiac arrest; and why hemolysis and renal effects may differ among PFA platforms and workflows.

Dr. Sharma also explores the FINE-HEART analysis of finerenone and sudden death, the LOSE-AF randomized trial of weight loss in older patients with persistent atrial fibrillation, occupational radiation exposure during pregnancy, the prognostic significance of skin thickness over cardiac implantable electronic devices, and a randomized crossover comparison of ivabradine and propranolol for POTS.

Rather than simply reciting percentages and P values, the discussion explains why each study was undertaken, how it was designed, what its principal statistical findings mean, where uncertainty remains, and how the results might—or might not—affect clinical practice. Each analysis concludes with the EP Edge take: a practical interpretation for physicians, trainees, nurses, allied professionals, and others caring for patients with heart-rhythm disorders.

The episode also previews the early September 2026 arrival of EPEdge.org and the EP Edge app. Built around Knowledge · Access · Humanity, the new platform will bring together EP Edge Analytics, EP Edge Academy, CME and MOC opportunities, EP Edge Rx, practical clinical resources, and the complete EP Edge newsletter archive.

And don’t miss next week’s must-listen collaborative issue with the Heart Rhythm Society.

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How long should anticoagulation continue after an apparently successful atrial fibrillation ablation? Should prophylactic pulmonary vein isolation be added during typical atrial flutter ablation in patients with heart failure? What do emerging data reveal about neurologic events, hemolysis, and renal safety with pulsed-field ablation?

In EP Edge® Journal Watch Issue 33, August 2026, Dr. Sharma provides a clinically focused and thought-provoking review of nine important cardiac electrophysiology studies published in Heart Rhythm and JACC: Clinical Electrophysiology.

This episode examines:

•  The proposed 8.1-month timing for oral anticoagulant discontinuation after successful AF ablation 
•  Prophylactic pulmonary vein isolation in patients with typical atrial flutter and heart failure 
•  Lesion delivery, irrigation rates, and neurovascular events with pulsed-field ablation 
•  PFA-associated hemolysis, acute kidney injury, and platform-specific renal safety 
•  Transvenous lead extraction outcomes in patients with prior sternotomy 
•  First-in-human vibration-based lead extraction 
•  The line-of-block pacing maneuver for distinguishing AV nodal from accessory pathway conduction 
•  The SCAAF-ERS electrocardiographic score for sudden cardiac arrest risk in atrial fibrillation 
•  A gain-of-function KCNJ8 variant linked with inherited and acquired J-wave syndromes 

Rather than simply listing study results, Dr. Sharma explains why each investigation was needed, what clinical uncertainty it attempted to resolve, how the methodology affects interpretation, and what the principal statistics mean in practical terms. Each paper concludes with the EP Edge Take, including the potential implications for current practice, the limitations that should temper interpretation, and the questions that future research must answer.

The episode also includes updates on the EP Edge® app, the new epedge.org website, and the upcoming EP Edge® Journal Watch collaboration with the Heart Rhythm Society.

Full references, study graphics, and the complete written analysis are available through the EP Edge® Journal Watch newsletter on LinkedIn and on Substack at epedge.substack.com.

Questions, suggestions, or concerns can be sent to [email protected].

Can anticoagulation be safely discontinued after successful atrial fibrillation ablation? Is the traditional prohibition against flecainide in structural heart disease too broad or does CAST remain an essential warning? And can AI-enabled ECGs, unipolar voltage mapping, and cardiac MRI improve how we detect AF and characterize arrhythmic substrate?

In EP Edge® Journal Watch Issue 32, Dr. Niraj Sharma examines important electrophysiology research published in Heart Rhythm and JACC: Clinical Electrophysiology, translating the methodology, statistical findings, limitations, and clinical implications into practical insights for electrophysiologists and cardiovascular clinicians.

Topics include:

• Discontinuing oral anticoagulation after AF ablation
• The clinical and economic consequences of delayed AF ablation
• Estimating AF burden after several AF-free monitoring days
• Multicenter validation of an AI-enabled ECG model for predicting AF
• Unipolar voltage mapping and lesion durability after pulsed field ablation
• High-density electroanatomic mapping versus cardiac MRI in nonischemic cardiomyopathy
• How CAST changed the direction of flecainide research
• Class Ic antiarrhythmic therapy after PCI
• Reconsidering flecainide in selected structural heart disease phenotypes
• Amiodarone-associated thyrotoxicosis in patients with pre-existing hypothyroidism

The episode separates statistical association from causal evidence and asks what these findings should and should not change in current practice. It also outlines the prospective trials needed to determine whether anticoagulation withdrawal, AI-guided AF screening, voltage-guided PFA, and phenotype-based flecainide prescribing can improve clinically meaningful outcomes.

Dr. Sharma also previews the next collaborative EP Edge® Journal Watch issue with the Heart Rhythm Society, the forthcoming EP Edge® app, and the new epedge.org platform—bringing podcasts, newsletters, EP Edge Rx, EP Edge Academy, and additional clinical and patient-focused resources into one accessible ecosystem.

References, graphics, and the complete written analysis are available through EP Edge® Journal Watch on LinkedIn and Substack:

https://epedge.substack.com

Questions, suggestions, or concerns: [email protected]