Disclaimer: 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 everyone, this is Doctor. Sharma and welcome back to EP Edge Journal Watch. Thank you for joining me for issue 19 where we move well beyond the rhythm strip and look at atrial fibrillation, pulsed field ablation, embolic risk, physiologic pacing, ventricular fibrillation precursors, and even rescue strategies in refractory ventricular tachycardia. Let's begin with a provocative question. When a patient presents with new onset atrial fibrillation, are we just seeing an atrial arrhythmia or could we be seeing a marker of broader systemic disease?
The first study, from Al Zahrani et al. In Heart Rhythm, explored whether new onset AF predicts incident cancer in a large real world dataset. The rationale is clinically relevant. AF and cancer often coexist, but the direction of that relationship remains unclear. So the investigators asked whether AF might function as an early signal of occult malignancy, and whether that signal persists over time rather than simply reflecting detection bias immediately after diagnosis.
This was a retrospective Tri Net X analysis. Patients had hypertension, type two diabetes, or coronary artery disease and anyone with prior malignancy was excluded. They created age stratified cohorts: age thirty-fifty, fifty-seventy, and seventy-eighty five years. Then they performed one to one propensity matching for demographics, comorbidities, medications, and selected lab variables. The primary endpoint was all cause incident cancer, with follow-up extending out to fifteen years.
The matched populations were large, about 67,000 per group in the youngest cohort, more than 510,000 per group in the middle cohort, and more than 882,000 per group in the oldest cohort. Cancer risk was higher in patients with AF across all age groups. The relative risk was two point nine nine in those aged thirty to fifty, one point seven nine in those fifty to seventy, and one point four nine in those seventy to eighty five, with all p values less than 0.001. Cancer free survival was also worse, with hazard ratios of 2.96, one point eight four and one point five three respectively, again all highly significant. Importantly, the association persisted even when cancers diagnosed within three months were excluded and it also persisted in analyses starting one year after AF diagnosis.
Now this does not prove causation. It is still observational and surveillance bias and residual confounding remain possible. But the signal is hard to dismiss. My EP Edge take is this: AF may at times be less an isolated rhythm diagnosis and more a systemic marker. This does not justify broad reflex cancer screening for every patient with new AF, but in someone with unexplained new AF, constitutional symptoms, anemia, inflammatory abnormalities, or no obvious atrial substrate, it should raise your level of suspicion.
In practice, the lesson is not panic. The lesson is clinical attentiveness. Next, let's move to pulsed field ablation and the blanking period. For years, the ninety day blanking interval after AF ablation has been treated almost as doctrine. Early recurrence was often dismissed as inflammatory noise, particularly after thermal ablation, but with pulsed field ablation, tissue injury and lesion maturation may behave differently.
So the question becomes, Does the classic blanking construct still make sense in the PFA era? Rodriguez Riascos et al. Publishing in Europace examined whether early recurrence after PFA at 30, sixty, and ninety days predicts later ablation failure strongly enough to challenge the usual framework. This was a retrospective multicenter Mayo Clinic health system cohort of eleven sixty two consecutive patients undergoing PFA for atrial fibrillation. The primary endpoint was AF free survival and recurrence was defined as ECG documented AF lasting more than thirty seconds.
The investigators specifically evaluated recurrence within thirty, sixty and ninety days and also examined a subgroup with implanted rhythm monitors or external monitoring. Overall, one year AF free survival in the cohort was seventy percent. Early recurrence occurred in eight point one percent by thirty days, eleven point one percent by sixty days, and fourteen point eight percent by ninety days. But the key finding was not just that early recurrence mattered, it was how strongly it mattered. Early recurrence predicted later recurrence beyond ninety days with a hazard ratio of 5.9 if it occurred within thirty days, 6.6 within sixty days, and 9.1 within ninety days, all with p values less than 0.01, and in patients with implanted devices and one year follow-up, recurrence within thirty days was associated with AF burden of at least one percent or repeat ablation at one year, with an odds ratio of twenty five point zero and a ninety five percent confidence interval from six point six to one hundred and twenty six point eight.
Now this is still retrospective and monitoring was not uniform, so we should not overstate management implications. But the EP Edge take is that a thirty day recurrence after PFA is no longer easy to dismiss. In a nonthermal lesion set, recurrent arrhythmia may reflect incomplete lesion durability or non pulmonary vein substrate rather than transient inflammation alone. In practice, I would say this: Don t treat early recurrence after PFA as automatic reassurance territory. It should trigger attention, closer surveillance, and a more thoughtful follow-up strategy.
The ninety day interpretive amnesty is looking increasingly difficult to defend without qualification. That brings us naturally to one of the most important comparative ablation trials in this issue. BEAT pulsed field ablation has moved very quickly from disruptive technology to mainstream clinical use. The remaining question is no longer whether it works, the real question is whether it performs better than a serious modern radiofrequency comparator when both are executed well. Jace and colleagues in the European Heart Journal randomized patients with drug resistant paroxysmal AF to pentaspline PFA or point by point radiofrequency ablation using the CLOSED protocol.
This was an open label, multicenter, randomized superiority trial across nine high volume European centers. Two ninety two patients were randomized and two eighty nine were analyzed, 145 in the PFA arm and 144 in the RFA arm. The primary endpoint was single procedure success at twelve months defined as freedom from atrial arrhythmia recurrence of at least thirty seconds, cardioversion, repeat ablation, or resumption of class I or class III antiarrhythmic therapy after a sixty day blanking period. Follow-up was reasonably rigorous including weekly cardiac tracings, twenty four hour Holters, systematic ECGs, and symptom triggered recordings. The result: efficacy was essentially identical.
Single procedure success was seventy seven point two percent with PFA and seventy seven point six percent with RFA. The adjusted difference was 0.9%, with a 95% confidence interval -8.2 to plus 10.1 and a p value of 0.84, so no superiority signal. But procedure efficiency strongly favored PFA. Procedure time was fifty nine minutes versus ninety eight minutes and left atrial dwell time was thirty nine versus seventy seven minutes. Serious procedure related adverse events occurred in three point four percent with PFA versus seven point six percent with RFA.
There were no deaths, no strokes, and no persistent phrenic nerve palsy in either group. But in the RFA arm, there were two tamponades: one esophageal bleed, two cases of severe pulmonary vein stenosis above seventy percent, and twelve cases of at least fifty percent pulmonary vein narrowing on imaging. The EP Edge take is that BEAT, parox AF, validates PFA as an efficacy matched alternative to optimize contemporary RFA, while shifting time and some safety signals in a favorable direction. But it also tells us something sobering: neither arm broke through the modern efficacy ceiling both landed around seventy seven percent. So the next leap forward may not come from energy source tribalism.
It may come from better substrate selection, better patient selection and more rigorous risk factor modification. In practice, PFA now looks validated, not speculative. Let's stay in the PFA world, but now move into the redo setting and the question of posterior wall isolation. One of the clinical risks with the new technology is that technical ease starts to outrun evidentiary discipline. Posterior wall isolation is now easier to perform with pentaspline PFA, especially during redo ablation.
But the real question is simple: does adding more lesion set actually help? Badercher et al. In heart rhythm compared redo pulmonary vein isolation alone versus redo pulmonary vein isolation plus posterior wall isolation in patients undergoing repeat AF ablation who had only one or two reconnected pulmonary veins. This was a retrospective analysis from the Swiss AFPVI registry with prospective enrollment from two tertiary Swiss centers. After propensity matching, they studied two forty four patients, one hundred and twenty two treated with redo PV isolation alone and one hundred and twenty two with redo PVI plus posterior wall isolation.
The primary endpoint was recurrence free survival from AF, atrial tachycardia or atrial flutter after a sixty day blanking period. The procedural data clearly favored the simpler strategy. Procedure duration was fifty four minutes with pulmonary vein isolation alone versus eighty minutes with PV isolation plus posterior wall isolation. Left atrial dwell time was thirty eight versus sixty minutes. Fluoroscopy time was five versus twelve minutes.
All of these differences were statistically significant, with p values less than point zero zero one. Acute procedural success was one hundred percent in both groups. Major complications were rare and identical, one event in each group, and at a median follow-up of three seventy days, arrhythmia free survival was similar, sixty nine percent with pulmonary vein isolation alone and seventy two percent with pulmonary vein and posterior wall isolation, with no significant difference, so the EP Edge take is straightforward. Technical feasibility is not clinical justification. In this selected redo population where the recurrence phenotype still looked largely pulmonary vein driven, adding posterior wall isolation increased time and fluoroscopy without improving rhythm outcome.
In practice that means this: when only one or two veins have reconnected and the recurrence story still looks PV mediated, re isolate the veins first. Do not reflexively add posterior wallwork, just because PFA makes it easy. Now let's turn from lesion sets to embolic risk. With one of the heaviest safety papers in this issue, the EMBOL-AF Global Registry. Most discussions of AF ablation complications focus on tamponade, esophageal injury, phrenic nerve palsy, or pulmonary vein stenosis.
But when patients think about what they fear most, stroke is often at the top of the list, and until now, we have lacked a contemporary large scale global registry to characterize that risk well. Castrayon Castrayon et al. Publishing in the European Heart Journal assembled a retrospective global registry through the European Heart Rhythm Association Scientific Committee. They collected data from two zero four centers in 56 countries covering three and thirty five thousand seven hundred and forty three AF and left atrial flutter ablation procedures performed between 2017 and 2024. After adjudication, they identified five fifty symptomatic embolic events in five forty seven patients.
The overall incidence of symptomatic embolic events was zero point one six percent, with a ninety five percent confidence interval from 0.15 to 0.18. Most were cerebral, about ninety four percent. Peripheral emboli accounted for five percent and combined cerebral and peripheral events for one percent. Timing mattered: seventeen percent occurred intra procedurally, seventy eight percent occurred within seventy two hours, but notably twenty three percent were only diagnosed after hospital discharge. Risk was higher in non paroxysmal AF, and crude registry level event rates differed by energy source: 0.16% for radiofrequency, 0.16 for cryoballoon, zero point two five percent for PFA, and zero point eight eight percent for laser balloon.
But those comparisons are hypothesis generating, not definitive, because denominator level procedural and patient differences remain substantial. What really stands out is the clinical weight of these events. At three months, thirty five percent of patients had persistent sequelae and three percent had died. My EP Edge take is that EMBOL-AF restores scale to a rare but devastating complication. An event rate of zero point one six percent may sound small until you realize that more than one third of affected patients remain neurologically impaired.
The practical consequences are important: First, discharge counseling and early neurologic vigilance are part of embolic risk management because nearly one in four events appear after discharge. Second, center process matters, anticoagulation quality, sheath handling, air management, and procedural discipline probably matter more than simplistic energy source narratives. Rare does not mean trivial. Staying with thromboembolic risk, the next study asks a different but very practical question: Are we overimaging patients before ablation? In many programs, pre procedural transesophageal imaging is still performed very broadly to exclude left atrial appendage thrombus, even in the direct oral anticoagulant era, but the yield of that strategy may be quite variable depending on phenotype.
Barbarossa et al. In pacing and clinical electrophysiology studied determinants of left atrial thrombus in patients undergoing catheter ablation for atrial fibrillation and atrial flutter. This was a single center observational cohort of five eighty six consecutive patients who underwent TE before AF or atrial flutter ablation between January 2019 and April 2024. TE was performed in patients with less than three weeks of optimal anticoagulation, persistent AF or paroxysmal AF with a CHADS VASc score of at least two. The primary outcome was the presence of left atrial thrombus.
Thrombus prevalence was two point four percent (fourteen out of five eighty six patients) and all clots were located in the left atrial appendage. Notably, there was no thrombus identified in any atrial flutter patient in this cohort. On univariate analysis, persistent AF carried an odds ratio of four point three zero eight, coronary artery disease three point six two six, heart failure three point four three four, and higher systolic pulmonary artery pressure also increased risk. Higher left ventricular ejection fraction was protective, and an EF below 50% emerged as the best cutoff associated with higher thrombus risk. The EP Edge take is not imaging nihilism, it is selective imaging.
This paper argues against indiscriminate pre ablation TEE in every patient. The yield was low overall, zero in atrial flutter here, and concentrated in the exact kinds of patients we already suspect are higher risk: persistent AF, structural disease, heart failure, lower EF, coronary disease, and elevated pulmonary pressures. In practice, if you have a flutter patient without structural disease who has been appropriately anticoagulated, routine TEE becomes increasingly difficult to justify, but in persistent AF with impaired ventricular function or broader structural disease, imaging still has clear value. Next, let's move into digital monitoring and the concept of event triggered anticoagulation. This is an attractive idea in theory: detect AF in real time, alert the patient and potentially guide anticoagulation around the episode, but the concept collapses immediately if detection is unreliable or the patient is not actually notified.
That is exactly what the SMART- ALERT study set out to examine. Bryosa, Igala and colleagues in Heart Rhythm tested whether an implantable cardiac monitor integrated with bespoke cloud based software and separately two wearable platforms could detect AF episodes longer than thirty minutes and notify patients reliably enough to support future episode guided anticoagulation workflows. This was a single center feasibility study. In phase I, 50 participants used a Link2 implantable monitor connected to SMART Alert software. In phase II, participants were allocated to either an Apple Watch or a CartRing, with the implantable monitor serving as the reference standard.
The main outcomes were notification success, acknowledgment timing, adherence, and wearable positive predictive value. Across four thousand nine hundred and forty three AF episodes detected in thirty one participants, the SMART Alert software successfully notified 511 of six ninety one eligible AF episodes, a seventy four percent notification success rate, and acknowledgment was excellent at ninety nine point six percent. But wearable performance was poor. The Apple Watch detected and notified only seventy six of three eighty nine qualifying episodes (about 19.5% ), the KartRing detected 72 of four seventy four (about 15.1% ). The Apple Watch had a much higher positive predictive value than the KartRing (69.7 versus 20.6% ), with P less than 0.001.
Adherence was also a major limiter. Average wear compliance was 66.3% for Apple Watch and only 23.9% for KartRing. Large proportions of AF episodes were missed simply because the devices were not being worn. The EP Edge take is clear: current passive consumer wearables are not ready for episode guided anticoagulation. The more promising signal is the implantable Monitor Plus software ecosystem, which shows that real time notification is feasible but still vulnerable to connectivity and workflow failures.
In practice, wearable alerts remain a wellness adjunct, not yet a dependable anticoagulation workflow. That distinction matters, especially as the concept gets more attention. Now let s move from atrial rhythm monitoring to pacing strategy in atrioventricular block with the MELOs reloaded study. The pacing conversation has changed. For patients with AV block and preserved or mildly reduced ejection fraction, we are no longer just asking whether physiologic pacing is feasible.
We are increasingly asking whether conventional right ventricular pacing should still be considered the default. Jastaszewski et al. In the European Heart Journal compared left bundle branch area pacing with right ventricular pacing in patients with AV block, left ventricular ejection fraction above 40%, and ventricular pacing burden above twenty percent. This was a multicenter European registry based analysis. After one to one propensity matching, three thousand three hundred and eighty two patients were included, sixteen ninety one with left bundle branch area pacing, and a similar number with right ventricular pacing.
The primary endpoint was all cause mortality and the secondary endpoint was heart failure hospitalization plus CRT upgrade. At four years, Kaplan Meier analysis showed an absolute survival difference of eleven point eight percent in favor of LBBAP with P 0.001. In multivariable analysis, LBBAP was associated with lower mortality, hazard ratio 0.53, with a ninety five percent confidence interval from 0.42 to 0.65. The combined endpoint of heart failure hospitalization upgrade was also lower, four point six percent versus eleven point two percent, again with a hazard ratio of 0.53, but one of the most important observations was internal to the left bundle branch area pacing group itself. Failure to confirm true left bundle branch capture, meaning left ventricular septal pacing rather than genuine conduction system capture, independently predicted higher mortality, with a hazard ratio of one point eight five.
That is the operational heart of this paper. The EP Edge take is not simply that left bundle branch area pacing looks better than right ventricular pacing. It is that capture quality matters. Conduction system pacing is not a branding exercise. True physiologic capture has to be demonstrated.
In practice for AV block with expected high pacing burden and ejection fraction above 40%, LBBAP pacing is moving from appealing option toward preferred default but only in hands that can verify real conduction system engagement. The next paper shifts us into the ventricular space and offers a useful challenge to how we think about ventricular fibrillation initiation outside the hospital. Most of our mental models for VF precursors come from inpatient telemetry, ICD electrograms or sudden death Holter studies, but ambulatory telemetry offers a different physiologic window and perhaps a different precursor profile. Grigoriadis, Pristowski, and Wadwa, writing in the Journal of Cardiovascular Electrophysiology, analyzed precursor arrhythmias of ventricular fibrillation in the ambulatory setting using Philips M. Cot data from 2021 through 2022.
They reviewed two seventy one technician labeled VF events, but after adjudication only seventy one represented true VF. The first deviation from each patient's baseline rhythm was categorized as ectopy, repolarization change, rate dependent change, or intraventricular conduction delay. Ectopy was the most common precursor category seen in thirty seven percent. Repolarization changes were seen in twenty five percent, rate dependent changes in twenty four percent, and intraventricular conduction delay in fourteen percent. Within repolarization abnormalities, ST depression occurred in thirteen percent, ST elevation in eight percent, and QTC prolongation above five hundred milliseconds in four percent.
Bradycardic and conduction related precursor signals were also notable, with sinus arrest in ten percent and third degree AV block in eleven percent. Perhaps the most surprising finding was that monomorphic VT preceded VF in only thirty eight percent of cases, lower than classic inpatient or Holter based expectations. The EP Edge take is that ambulatory VF precursor biology appears broader than the simple VT to VF model many of us carry. Ectopy, dynamic ST or QT changes, and brady conduction abnormalities may be at least as important as organized monomorphic VT and some outpatient deterioration patterns. In practice, remote monitoring programs may need to take escalating PVC burden, repolarization shifts, or abrupt conduction slowing more seriously than they often do now.
This is hypothesis generating, yes, but it may eventually reshape how we triage warning signals. We'll close the trial review with a small but very intriguing paper on drug refractory ventricular tachycardia and conduction system pacing as a rescue strategy. In advanced cardiomyopathy with wide QRS, VT storm, or hemodynamic instability, VT ablation may be possible, but not always strategically wise as the first move. In some of these patients the substrate problem is not just scar, it may also include dyssynchrony, failed biventricular pacing, or an unaddressed resynchronization opportunity. Herwig et al.
In Heart Rhythm described five patients with advanced cardiomyopathy, mean age 71 years and mean ejection fraction eighteen percent, treated with conduction system pacing based CRT as an alternative to immediate VT ablation, four had non ischemic cardiomyopathy, two were in cardiogenic shock, and three were in VT storm at the time of the procedure. The pacing approaches included his bundle pacing in one patient, left bundle branch area pacing in three, and left bundle branch pacing optimized CRT in one. The physiologic changes were striking. QRS duration narrowed from one hundred and forty eight plus or minus twelve milliseconds before CSP to one hundred and twenty plus or minus eight immediately after, and 123 plus or minus six at latest follow-up with p less than point zero zero one. QTc shortened from five zero three plus or minus fourteen milliseconds to four fifty plus or minus 26.
Ejection fraction improved from 15 plus or minus 10% to 39 plus or minus 16% with P less than 0.05, and ICD therapies fell dramatically from two thirty four VT or VF terminations in the year before CSP to just seven in the first year after. Now this is a tiny uncontrolled case series. Regression to the mean, antiarrhythmic adjustment, and general heart failure stabilization could all contribute. So this is absolutely not a replacement for ablation paper, but the EP Edge take is that physiologic resynchronization may, in selected unstable wide QRS cardiomyopathy patients, serve as a rescue maneuver or a bridge that makes later ablation safer and more tolerable. In practice, the message is to broaden the bailout toolkit.
In the right patient, especially with advanced non ischemic disease or dyssynchrony related instability, conduction system pacing may sometimes be the safer first move. So what is the bottom line from this issue? Taken together these studies remind us that electrophysiology is increasingly systemic, procedural and physiologic all at once. AF may signal broader disease. PFA demands recalibration rather than blind enthusiasm.
Stroke risk remains rare but heavy, selective imaging and smarter monitoring matter, and conduction system pacing continues to expand from preferred pacing strategy to potential rescue tool, And on the ventricular side, both ambulatory VF precursors and CSP based rescue in refractory VT push us to think beyond older, narrower arrhythmic models. All references and graphics are available on the LinkedIn newsletter, EP Edge Journal Watch as well as on Substack at epedge. Substack . com. Email comments and suggestions to epedgcast@gmail . com. Thank you again for listening and thank you for being part of EP Edge.
Bye till the next episode and take care.