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Monthly clinical deep analysis in cardiac electrophysiology: AF, VT, SVT, ablation, devices, antiarrhythmic drugs, and high-impact trials. The Signal: physician-level analysis that identifies what matters in EP and translates evidence into clinical practice.
EP Edge™: The Signal is the flagship monthly podcast from EP Edge, delivering structured, expert-level interpretation for electrophysiologists, cardiologists, fellows, and clinically engaged practitioners. Each episode goes beyond summaries to integrate evidence across trials, guidelines, mechanisms, and real-world practice.
Episodes cover the full spectrum of electrophysiology, including atrial and ventricular arrhythmias, supraventricular tachycardias, antiarrhythmic pharmacology, pacing and defibrillator strategies, mapping and ablation technologies (including pulsed field ablation), and emerging data shaping clinical decision-making. This is not a news recap—it is a curated synthesis focused on what truly changes practice.
Content combines mechanistic insight, cross-trial evidence review, critical appraisal of methodology and outcomes, and practical application in the EP lab and clinic.
EP Edge™: The Signal complements the weekly EP Edge™: Journal Watch by providing deeper analysis and clinical synthesis. For patient-focused education, explore EP Edge™: Heart Talk.
Available as both podcast and newsletter via EP Edge on LinkedIn and Substack: https://epedge.substack.com/
Hello everyone and welcome back to the EP Edge podcast. I am Doctor. Sharma, this is Pulse field ablation part two. In part one we stayed mostly on the engineering side, what electroporation is, why the waveform matters, why tissue selectivity is the core promise, and why PFA has been marketed as safer and faster than thermal energy. Today we shift from physics to patients.
Niraj Sharma:Part two is a longer than usual episode we have a lot to cover especially with the arrival of two new PFA trials, the INSIGHT and the PULSAR. We will delve into pivotal clinical trial evidence, how the major platforms earned regulatory confidence, what the trials actually measured, and what we should and should not conclude when we see a twelve month success rate in a paper or on a slide deck, and just to set expectations. I am going to be detailed but I am going to keep it conversational. If you are a nurse or an allied professional listening, I will define terms as we go. If you are a fellow or an electrophysiologist, I will slow down at the methodological gotchas that matter when you compare platforms.
Niraj Sharma:Alright, let's get into it. Before we talk about specific trials, I want to give you a mental framework because this is where people get misled. The interpretive trap is assuming that freedom from atrial fibrillation at twelve months is a uniform construct. It is not. Across the PFA programs, the studies differ in at least five ways that materially change the measured event rate: one.
Niraj Sharma:The patient phenotype: paroxysmal versus persistent atrial fibrillation two. The lesion set pulmonary vein isolation only versus pulmonary vein isolation plus posterior wall or other substrate work three. The endpoint definition: pure rhythm recurrence versus a composite that includes drug escalation, cardioversion, and redo ablation. Four. The monitoring density: intermittent EKG and Holter monitoring versus continuous implantable monitoring.
Niraj Sharma:Five. The statistical framework: randomized non inferiority comparisons versus single arm performance goal designs. Let me translate a few of those in plain English. A composite endpoint is when failure includes not only a documented arrhythmia but also what clinicians do about it, like starting an antiarrhythmic drug, increasing a dose, performing cardioversion, or bringing the patient back for a redo ablation. That tends to lower the measured success rate compared with arrhythmia recurrence alone and it injects practice pattern variability.
Niraj Sharma:Monitoring matters even more. If you check a patient with a twelve lead EKG at three, six, and twelve months and you do one or two Holters, you will miss asymptomatic recurrence. If you implant a continuous monitor, you detect more events. So when you see two trials with different monitoring, the absolute success percentages are not directly comparable, sometimes not even close. Finally, on design, a randomized trial tells you how the new energy compares with the comparator under the same rules.
Niraj Sharma:A single arm, performance goal trial tells you We beat a predefined bar, but it does not tell you the new energy is better than the best contemporary thermal workflows. That doesn't make single arm trials useless. It just means we have to interpret them with discipline. With that framework, we'll go in roughly chronological U. S.
Niraj Sharma:Approval order and then finish with the newest wave of studies. First up, Medtronic Pulse Select, approved 12/13/2023, built on the Pulsed AF pivotal trial. PULSED AF is a global multicenter non randomized pivotal study with two separate cohorts: paroxysmal atrial fibrillation and persistent atrial fibrillation where episodes last longer and the substrate is typically more complex. They enrolled 150 patients in each cohort for the primary analysis. Now a key point about who they studied: patients with very large left atria, long standing persistent atrial fibrillation, and significant structural disease were generally excluded, so this is not the sickest end of the spectrum.
Niraj Sharma:That matters for generalizability. The procedure itself is fairly representative of modern PFA workflows. Pulmonary vein isolation was achieved acutely in essentially all veins, and the protocol mandated a twenty minute waiting period with reassessment of entrance block, which is important. In plain terms, they didn't just touch the vein and declare victory. They waited to see if early reconnection showed up.
Niraj Sharma:How did they follow patients? It was not continuous monitoring. They used weekly and symptom driven transtelephonic monitoring plus scheduled 12 lead EKGs at three, six, and twelve months and twenty four hour Holters at six and twelve months. So this is reasonably rigorous for a pivotal IDE error trial but it is still intermittent. What counted as success?
Niraj Sharma:This is where the nuance is. The primary effectiveness endpoint was a composite through twelve months after a ninety day blanking period. Failure could be arrhythmia, recurrence, but it could also be cardioversion, repeat ablation outside blanking, or escalation or initiation of certain class I or class III antiarrhythmic drugs. In other words, it's not purely drug free rhythm freedom. On results, the twelve month composite effectiveness was about sixty six percent in paroxysmal atrial fibrillation and about fifty five percent in persistent atrial fibrillation.
Niraj Sharma:If you isolate arrhythmia recurrence alone after blanking, the numbers look a bit higher. So again, composite endpoints and monitoring density drive the headline number. Safety and pulsed AF looked strong, serious device or procedure related adverse events were rare, and the catastrophic thermal complications, atrioesophageal fistula and significant pulmonary vein stenosis, were not observed. They also had sub studies. Brain MRI showed silent lesions in a minority, and imaging did not show moderate or severe pulmonary vein stenosis in the imaged subset.
Niraj Sharma:So how should we interpret Pulse Select's pivotal dataset? It supports feasibility, procedural efficiency, and a low major complication rate in selected populations with outcomes that look in the range of contemporary thermal results bearing in mind the endpoint and monitoring structure. It does not, by design, answer better than thermal because there is no randomized comparator. Next, Boston Scientific Farapulse approved 01/31/2024, anchored by the ADVENT randomized trial in paroxysmal atrial fibrillation. ADVENT is important because it is one of the cleanest apples to apples comparisons we have in PFA.
Niraj Sharma:It was a multicenter, randomized, one to one, single blind, non inferiority pivotal trial. Patients did not know which energy they received, endpoints were adjudicated, and the thermal comparator was contemporary, either radiofrequency or cryoballoon, with sites committed to one modality. They enrolled over six eighty patients who underwent ablation, with roughly three zero five in the PFA arm and three zero two in the thermal arm. The population was symptomatic, drug refractory paroxysmal atrial fibrillation, adults up to seventy five. Baseline risk looked like a typical ablation trial cohort: early 60s on average, moderate comorbidity, and a relatively low to moderate stroke risk score.
Niraj Sharma:Ablation strategy was pulmonary vein isolation in both arms with a required waiting period and confirmation of entrance block. CTI ablation for typical flutter was common in both arms. Additional non pulmonary vein ablation was rare and slightly more common in the thermal group. Monitoring was intermittent but denser than just two halters. They used weekly remote event monitoring after the three month blanking period plus symptom triggered recordings, and they did seventy two hour Holter monitoring at six and twelve months.
Niraj Sharma:Still, it is not continuous, so the absolute recurrence rates are still partially surveillance limited. The primary effectiveness endpoint, again, was a composite. It included acute procedural failure, documented atrial arrhythmia recurrence after blanking, antiarrhythmic drug use or cardioversion after blanking, amiodarone at any time, or repeat ablation through one year. So the trial measures a clinically pragmatic was the strategy successful without needing major rescue steps, not just electrogram defined recurrence. One year primary effectiveness success was about seventy three percent for PFA and seventy one percent for thermal.
Niraj Sharma:The difference was small and the trial met non inferiority with a very high posterior probability. The point estimate is essentially equal, so ADVENT is not a superiority story, it is: PFA performs at least as well as best practice thermal ablation and paroxysmal AF within this monitoring and endpoint structure. On safety, serious adverse events were low in both arms and met non inferiority. But we do need to say this out loud: there was one death in the PFA arm associated with the tamponade and resuscitation cascade. There were also tamponades in the PFA arm and none in the thermal arm in the trial dataset.
Niraj Sharma:That doesn't mean PFA causes tamponade, it means mechanical complications still exist and they remain a key safety frontier. Thermal had its own signal. Persistent phrenic nerve palsy occurred in a small number in the thermal arm and none in PFA. Neither group had atrioesophageal fistula or clinically significant pulmonary vein stenosis. A particularly interesting secondary endpoint was pulmonary vein narrowing.
Niraj Sharma:They measured change in aggregate pulmonary vein cross sectional area from baseline to three months. PFA had minimal change (under 1% ), while thermal showed a larger average reduction. Mechanistically, that's consistent with the idea that non thermal energy may reduce the propensity for vein stenosis. ADVENT also had a brain MRI substudy. Silent lesions were seen in a minority of PFA patients and not seen in the thermal subset, but the sample sizes were small.
Niraj Sharma:For me, the broader takeaway is silent cerebral embolic events remain an ecosystem problem: catheters, air, anticoagulation, workflow, not just an energy source problem. Now still in the FerriPulse ecosystem, we have Advantage AF in persistent atrial fibrillation and the manifest registries. These are not randomized comparisons, they're about generalizability, lesion set feasibility, and rare safety signals at scale. ADDvantage AF is an FDA IDE program in symptomatic persistent atrial fibrillation and importantly, the ablation strategy in the pivotal cohorts was pulmonary vein isolation plus posterior wall ablation. So right away, this is not directly comparable to ADVANCE pulmonary vein isolation only paroxysmal trial The phase I dataset used an intermittent monitoring strategy, twice monthly transtelephonic monitoring plus symptom triggered transmissions, twenty four hour Holters at six and twelve months, and scheduled EKGs.
Niraj Sharma:The primary effectiveness endpoint was a composite after blanking, requiring freedom from documented atrial arrhythmia recurrence, no redo ablation, no cardioversion, and no new or escalated class I or class III antiarrhythmic drugs or amiodarone. The headline effectiveness number was in the low to mid 60s for that composite endpoint at twelve months exceeding the pre specified performance goal. Again, performance goal met is not better than thermal. It is: The strategy meets a predefined standard of effectiveness in persistent atrial fibrillation under this monitoring regime with this lesion set. Safety met its performance goal as well with a low serious adverse event rate.
Niraj Sharma:There are a couple of signals worth remembering because they show up across PFA programs: coronary spasm and hemolysis signals a small number. Most of the serious events in the phase I report were things like pulmonary edema and pericarditis. Catastrophic complications, atrioesophageal fistula and pulmonary vein stenosis, were not observed. Phase II incorporated implantable cardiac monitors. But here's the critical nuance: For the primary effectiveness endpoint, the continuous monitor data were deliberately subsampled to emulate intermittent monitoring.
Niraj Sharma:So even when an implantable monitor is present, the primary endpoint can be structured to behave like an intermittent trial. That design choice matters if you are trying to compare success rates across studies. Now let's talk post approval safety, the manifest registries, because this is where scale helps us see rare events. Manifest was an early European post approval registry with about fifteen sixty eight consecutive patients. Major adverse events were under two percent.
Niraj Sharma:The dominant hazards were still the classic ones, tamponade around one percent and stroke around four tenths of a percent. There was one death, and the reassuring signal, again, was zero atrial esophageal fistula and zero symptomatic pulmonary vein stenosis reported. MANIFEST 17Ks scaled this up dramatically, over seventeen thousand cases. Major adverse events were under one percent. Deaths were rare.
Niraj Sharma:Stroke was around onetenth of a percent. Tamponade was a few tenths of a percent. Coronary spasm showed up. And importantly, hemolysis associated renal failure requiring hospitalization was detected. Rare, but not zero.
Niraj Sharma:Again, no atrial esophageal fistula and no pulmonary vein stenosis signals were reported. Then Manifest US, with over 40,000 patients across more than 100 institutions, pushed the same story into US routine practice. Overall, complications were well under one percent. Tamponade and stroke were each about oneten to twoten of a percent. Death was rare but present.
Niraj Sharma:Coronary spasm was present. An acute renal failure requiring dialysis consistent with severe hemolysis in a small subset was present, again very rare, and the absence of fistula and clinically significant vein stenosis persisted. So what's the net message from the MANIFEST datasets? PFA safety appears scalable, but it does not eliminate procedural risk. The energy may shift certain injury phenotypes downward, especially esophageal catastrophe, but the mechanical, thromboembolic, and workflow hazards remain, and at scale you start to see the very low frequency dose related signals like hemolysis and renal injury that smaller trials are underpowered to detect.
Niraj Sharma:Third, in our approval timeline, Medtronic Sphere nine, the Afera lattice tip system. Approved 10/24/2024. This is a different flavor of platform. It's a focal lattice tip catheter paired with a dedicated mapping and ablation ecosystem. The SPHERE, per AF IDE trial, is randomized one to one, single blind, and non inferiority.
Niraj Sharma:The population was symptomatic, persistent atrial fibrillation, refractory or intolerant to at least one class I or class III antiarrhythmic drug. They randomized over four hundred patients, with about two twelve in the investigational arm and two zero eight in the control arm, which was a contemporary focal radiofrequency platform. Both arms required pulmonary vein isolation. But here's a key methodological reality. Additional lesion sets were very common, especially in the investigational arm.
Niraj Sharma:Posterior wall lines, roof lines, inferior lines, mitral lines, CTI these were done frequently. So when you see a performance difference you have to ask, is this the catheter or is it more substrate modification. That's lesion set confounding. Monitoring was again non invasive and intermittent. Holters, EKGs, and trans telephonic transmissions with good compliance and core lab adjudication.
Niraj Sharma:The primary effectiveness endpoint was a composite through one year after blanking, including arrhythmia recurrence, redo ablation, cardioversion, and antiarrhythmic drug initiation or escalation. Primary effectiveness success was roughly seventy four percent in the investigational arm and sixty six percent in the control arm. Non inferiority was met. The absolute difference favored the investigational arm, but the confidence interval crossed zero, so statistically this is non inferior, with a suggestion of benefit. Safety was low and similar between arms and in the reported trial dataset, catastrophic complications, atrioesophageal fistula, pulmonary vein stenosis, tamponade, stroke were not observed.
Niraj Sharma:There was also a brain MRI substudy showing acute lesions in a small minority in both arms, with most resolving on follow-up imaging. So the clinical takeaway for SPHER-nine is a randomized persistent AF dataset, showing at least non inferior effectiveness to contemporary focal radiofrequency, with low complication rates but with heavy confounding from extensive adjunct ablation, especially in the investigational arm. It's a reminder that persistent AF outcomes are often about the overall strategy, not one magic energy source. Next, moving on to Johnson and Johnson Biosense Webster Verapulse approved in late twenty twenty four, built on the ADMIRE pivotal trial in paroxysmal atrial fibrillation. ADMIRE is a prospective multicenter single arm FDAIDE pivotal study, so again a performance goal framework, not a randomized comparison.
Niraj Sharma:The population was symptomatic drug refractory paroxysmal atrial fibrillation in adults up to seventy five, without prior ablation. The pivotal cohort treated was about two seventy seven patients. The index strategy was first time pulmonary vein isolation in everyone. Monitoring in ADMIRE is interesting because it blends consumer style technology with traditional methods. They used Cardia Mobile six lead recordings weekly early, then monthly later, plus symptom triggered recordings.
Niraj Sharma:They also did twenty four hour Holters at six and 12 and scheduled EKGs. Core lab adjudication was used, so the monitoring is still intermittent but with higher frequency patient driven captures than in many older thermal trials. The primary effectiveness endpoint was again a composite at twelve months: no acute failure, no use of a non study catheter, no repeat procedure except potentially one during blanking, no documented atrial arrhythmia recurrence after blanking, no new or escalated antiarrhythmic drug therapy, and no cardioversion after blanking. The headline Effectiveness success at twelve months was in the mid-70s, and Freedom from atrial tachyarrhythmia recurrence after blanking was also about seventy five percent. Safety events were low overall, with pericardial tamponade as the most common serious complication.
Niraj Sharma:A workflow note that's practically relevant: A substantial fraction of cases were performed without fluoroscopy, reflecting integration with contemporary mapping workflows. ADMIRE supports that a pentasplin PFA catheter can achieve good paroxysmal pulmonary vein isolation outcomes with acceptable safety in an IDE framework, but because it's single arm, the disciplined conclusion is meets performance expectations, not beats thermal. Fifth, Abbott Volt with U. S. Approval in December 2025 and an evidence package that includes a CE Mark study, twelve month follow-up presented at a major meeting, and an IDE program with acute results reported.
Niraj Sharma:The VOLT CE Mark investigation enrolled about one hundred and fifty patients with one hundred and forty six treated. It included both paroxysmal and persistent atrial fibrillation, roughly seventy percent paroxysmal and 30% persistent, and the lesion set was pulmonary vein isolation only. That's important. No posterior wall, no additional substrate lesions as a mandate. They also mandated a waiting period.
Niraj Sharma:Monitoring combined scheduled EKGs, biweekly transtelephonic monitoring, and a twenty four hour Holter at six months. Acute isolation metrics were excellent. Near universal acute pulmonary vein isolation with very high first pass isolation rates. Safety events were low, dominated by vascular complications and one tamponade, no deaths, no atrioesophageal fistula, no phrenic nerve injury, and no hemolysis signal in that early cohort. Alright, before we finish the Volt story, let's take a quick breath and recap where we are.
Niraj Sharma:Up to this point, the pattern is consistent across platforms. Acute pulmonary vein isolation is nearly universal. Safety has improved in meaningful ways, especially for the catastrophic thermal complications, but the one year efficacy numbers look broadly similar to contemporary thermal ablation when you compare like with like. After a short break, we'll come back and finish VOLT, especially the twelve month signal in paroxysmal versus persistent AF and then we'll move into Insight and PULSAR which are really about optimization and durability. Okay, quick break.
Niraj Sharma:Picking up where we left off, let's finish the Abbott Volt story because it's a nice example of how PFA can look phenomenal acutely while the longer term outcomes still obey the biology of atrial fibrillation. The first dataset is the Volt CE Mark program at six months. It was a prospective, multicenter, pre market investigation across 11 sites in Europe and Australia. 150 enrolled, 146 treated. About seventy percent were paroxysmal AF and about thirty percent persistent AF.
Niraj Sharma:The lesion set was pulmonary vein isolation only, with a mandatory twenty minute waiting period. Monitoring was structured but intermittent. Scheduled EKGs, biweekly transtelephonic monitoring, and a twenty four hour Holter at six months. Acute PV metrics were excellent. About ninety nine percent of pulmonary veins were acutely isolated and first pass isolation was about ninety eight percent per vein, with roughly 18 PFA applications per patient.
Niraj Sharma:Safety in that cohort. Primary safety events were about 2.7%, and the events included two major vascular complications, one tamponade and one pneumonia, and importantly, no deaths, no atrioesophageal fistula, no phrenic nerve injury, and no hemolysis signal in that early cohort. At six months, freedom from documented atrial arrhythmias looks strong, about eighty eight percent for paroxysmal and about seventy seven percent for persistent, and the composite effectiveness success was about eighty six percent for paroxysmal and seventy two percent for persistent. Then we move to the twelve month outcomes presented as part of that same CE mark cohort. Again one hundred and forty six total patients, one hundred and three paroxysmal and forty three persistent.
Niraj Sharma:At twelve months, freedom from documented atrial arrhythmias was about eighty three point five percent for paroxysmal and about fifty eight percent for persistent. And that drop in persistent is the key teaching point. If you do pulmonary vein isolation only in a substrate heavy population, even with elite acute isolation, the ceiling shows up again. They also reported durability signals in redo procedures. About ninety four point five percent were free from repeat procedures overall and among the veins assessed at redo, about ninety percent remained durably isolated (twenty seven of 30 veins).
Niraj Sharma:Useful, but remember redo based remapping is selected. It's not a universal remap substudy. Finally, the Volt AF IDE acute dataset gives you scale: three twenty patients, roughly half paroxysmal and half persistent, again pulmonary vein isolation only, no adjunctive lesions. Acute isolation was essentially universal, about ninety nine point five percent to ninety nine point eight percent per vein. First pass isolation was around ninety two percent in paroxysmal and about ninety percent in persistent.
Niraj Sharma:The workflow signal is also practical. A small fraction were zero fluoro and a meaningful minority were performed with conscious or deep sedation, with some cases avoiding propofol entirely. Safety in that acute IDE dataset: Primary safety events were about one point nine percent, including tamponades, pericarditis, a stroke, and a vascular complication, with no hemolysis or renal injury signal reported there. So taken together, Volt looks technically efficient and clinically credible, but it doesn't break the fundamental rule. Persistent AF remains persistent AF when the strategy is pulmonary vein isolation only.
Niraj Sharma:Okay, let's shift to what I called the latest wave, where the field is trying to optimize two things: first, intra procedural durability and second, patient movement and neuromuscular capture that can complicate sedation and catheter stability. The trial here is Insight PFA versus ablation index guided radiofrequency for pulmonary vein isolation in paroxysmal atrial fibrillation. And the comparator is important. Ablation index guided RF is not average RF, it s a best practice thermal workflow. Design wise, Incyte was prospective, multicenter, randomized, one to one, and non inferiority.
Niraj Sharma:They enrolled two eighty seven patients across 13 centers and about one hundred and forty one in the nanosecond PFA group and one hundred and forty two in the AI guided RF group completed follow-up. Here is the methodological feature I really like. There was a mandatory at least twenty minute waiting period after pulmonary vein isolation. And if a vein reconnected during that wait, they were required to re ablate, then re wait until stable block was confirmed. That design makes acute success less superficial than trials without mandated waiting.
Niraj Sharma:Follow-up rhythm surveillance was structured but intermittent. Patients had on-site visits at one, three, six, and twelve months with a twelve lead EKG and a twenty four hour Holter, and they were instructed to obtain an EKG promptly if symptoms suggested recurrence, so the trial detects clinically meaningful recurrence but is not continuous implantable monitoring. The primary efficacy endpoint was freedom from documented AF, atrial flutter, or atrial tachycardia, episodes lasting at least thirty seconds of class I and class III antiarrhythmics from the end of the three month blanking period through twelve months. Results were the classic modern story: about sixty five point five percent success for nanosecond PFA and about sixty four percent for AI guided RF. The adjusted difference was about plus two percent and the trial met non inferiority.
Niraj Sharma:Time to event estimates were essentially the same, mid-60s in both arms, with a hazard ratio around one. Translation ns PFA matched optimized RF but did not beat it. And the intra procedural durability signal is humbling. During the mandated waiting period per vein reconnection was in the low teens, roughly fourteen percent for nanosecond PFA and about twelve percent for AI guided RF. So even with advanced waveforms and careful protocols, acute reconnection is not zero.
Niraj Sharma:Durability remains the central constraint. Before we leave Insight, let's talk safety. And this is where we have to be a little nuanced. The headline was No significant difference in procedure related adverse events between nanosecond PFA and ablation index and no obvious catastrophic signal in that dataset, but InSight also surfaced a few mechanism relevant, very practical things. One was a transient ischemic type event that was felt to be consistent with an air embolism workflow issue and not necessarily the energy source, and there was a hemolysisphenotype when application counts got very high (think tea colored urine without overt renal failure.
Niraj Sharma:The reason I mentioned that is simple. It's a dose marker. It's the system telling you if you're doing too many applications, your efficiency is off. Now the limitations because they matter for interpretation. Rhythm monitoring was intermittent, EKGs plus limited Holters, so asymptomatic recurrence can be undercounted.
Niraj Sharma:It's a non inferiority design. So non inferior does not mean equal in every clinically relevant domain and the chosen margin always matters, and safety ascertainment can miss subclinical injury if you are not doing routine endoscopy or systematic PV imaging. Put those together and I think the right take home is nanosecond PFA is a legitimate optimized option for paroxysmal pulmonary vein isolation. The value proposition is plausibly workflow, speed and sedation flexibility more than a giant leap in rhythm outcomes. And that leads perfectly into our next study because it's basically the next attempt at solving the durability problem.
Niraj Sharma:The trial is PULSAR, an FDA IDE pivotal program using the Globe Spherical Array Catheter. The idea is to integrate high density electrodes plus contact assessment, both dynamic and static, and then tailor which electrodes deliver lesions, aiming for contiguous ontral coverage that translates into more durable PVI. Let s unpack Pulsar, because it s very representative of modern IDE philosophy: single arm, performance goal framework, with a composite effectiveness endpoint that tries to capture what we actually care about in clinic. The study was multicenter and prospective. Total enrollment was 183 patients, 19 were roll in, and 164 were the pivotal cohort used for the primary endpoint analyses.
Niraj Sharma:The population here was paroxysmal AF undergoing pulmonary vein isolation with the globe system spherical array catheter. Now the effectiveness endpoint was not simply arrhythmia free. To count as a success, a patient had to remain free of AF, atrial flutter, or atrial tachycardia episodes lasting thirty seconds or more through twelve months and avoid other failure modes, acute failure to isolate veins, repeat ablation or cardioversion, and new or increased doses of class I or class III antiarrhythmics. So it's clinically sensible but it's also stricter than many pure rhythm only definitions. How did they look for recurrence?
Niraj Sharma:Intermittent but structured. Weekly transtelephonic monitoring plus symptom triggered transmissions, twenty four hour Holters at six and 12, and 12 lead EKGs at three, six, and twelve months. Again, good surveillance but not continuous implantable monitoring. Acute performance looked strong. They achieved acute pulmonary vein isolation.
Niraj Sharma:And most veins (around 94% ) were isolated with the first pulse field application. The whole single catheter render and ablate concept is aimed at workflow efficiency and that efficiency showed up in their procedural time metrics as well. Safety was the standout. The primary safety event rate in the pivotal cohort was about zero point six percent (one event out of one hundred and sixty four). The one-sided upper 95% confidence bound was around 3.4, which stayed below the pre specified safety performance goal of fourteen percent.
Niraj Sharma:The single primary safety event was a hemorrhagic stroke identified immediately post procedure in a patient with major comorbidity risk. And the composite primary effectiveness success at twelve months was about seventy seven point eight percent, with the lower confidence bound still well above the pre specified efficacy performance goal of fifty percent. But remember what failure means in a composite endpoint. It's a blend of rhythm recurrence and management events like redo and drug escalation. Durability, the thing everybody really wants, was assessed with invasive remapping only in clinically indicated redo procedures, reporting purvein durability in those who returned.
Niraj Sharma:That's valuable, but it's not a universal remap cohort. So it informs, but it doesn't fully settle the durability question. Now I want to step back and answer the question that comes up every time we talk about these trials. If PFA is so much safer, why doesn't it dramatically improve efficacy? The honest answer is that the early enthusiasm around PFA was always driven more by safety than by a promise of cure.
Niraj Sharma:Across first in human studies, randomized trials, and real world registries, PFA has repeatedly shown a uniquely favorable safety profile, especially the near elimination of catastrophic thermal complications like atrioesophageal fistula and a reduction in collateral injury to structures like the phrenic nerve. That safety signal has replicated across platforms and geographies, which is why the field embraced it so quickly. But, and this matters, adoption has also revealed rare PFA specific issues, things like coronary vasospasm, transient ST segment changes, and concerns around microembolization. They're uncommon, but they're a reminder that no ablation technology is biologically inert. When you shift the energy source, you often shift the complication spectrum rather than abolish it.
Niraj Sharma:The bigger story, though, is efficacy. When you look across trials, freedom from recurrent atrial arrhythmia is remarkably similar between PFA and contemporary thermal ablation, and that looks less like a catheter problem and more like a disease problem. In other words, we may be hitting a biologic ceiling. Atrial fibrillation is not purely a pulmonary vein phenomenon. It's a progressive atrial cardiomyopathy.
Niraj Sharma:Fibrosis, atrial dilation, adipose infiltration, inflammation, autonomic imbalance, genetic susceptibility. The whole ecosystem. So if the sustaining mechanisms extend beyond the pulmonary veins, then making pulmonary vein isolation safer and more elegant, however impressive, should not automatically produce a step change in long term success. Seen through that lens, the value proposition of PFA becomes clearer and, frankly, more honest. The principal advantages based on current evidence are safety and speed, rapid lesion delivery, simplified workflows, shorter procedure times, and reduced anesthesia burden.
Niraj Sharma:That translates into higher lab throughput and the ability to offer ablation more broadly, with greater operator confidence. So PFA may not cure more patients per procedure, but it enables safer, scalable, high volume AF care, potentially allowing earlier intervention in the disease course and better access. Whether the gain in efficacy comes from substrate directed strategies, upstream risk factor modification, biologic or metabolic therapies, or artificial intelligence guided patient selection is an open question. What is increasingly clear is that the next leap will not come from faster pulses or newer catheters alone, but from a deeper understanding of why ablation fails in the first place. Alright, let's land the plane.
Niraj Sharma:In part one of this series, we lived in the engineering, waveforms, pulse trains, field strength, tissue selectivity, and why electroporation behaves so differently from thermal energy. The core message there was that PFA changes the risk profile by design. In part two, we shifted to the pivotal evidence, the real world question of what happens when you put these systems into everyday clinical practice and follow patients out to a year. Across the platforms, the themes repeat: acute PVI is almost universally excellent, safety is meaningfully improved for the classic catastrophic complications, and efficacy, especially in more advanced substrate, still looks like it is governed by the underlying biology of atrial fibrillation. If you want the numbers, the tables, and the visual comparisons, I am posting an abridged version with graphs and infographics on LinkedIn.
Niraj Sharma:The full detailed newsletter write up is available at epedge.substack.com and I genuinely like to hear from you. If you have questions, suggestions or you want me to clarify a specific trial methodology or monitoring strategy, email me at epedgecastgmail dot com. Thank you for listening and for being part of the EP Edge community. Bye for now and I'll see you in part three.