Subscribe
Share
Share
Embed
Welcome to EP Edge Journal Watch, where cardiac electrophysiology meets evidence, precision, and perspective.
Hosted by Dr. Niraj Sharma, this weekly podcast distills high-impact cardiovascular and Cardiac Electrophysiology and arrhythmia research into clear, clinically meaningful insights. Each episode goes beyond headlines and abstracts to uncover what new studies actually mean for patient care, decision-making, and the future of electrophysiology.
What EP Edge Journal Watch stands for:
Evidence-based practice
Precision electrophysiology, arrhythmias analysis
A forward-thinking, edge-driven approach to how we interpret and apply data in real-world clinical settings.
Whether you’re an electrophysiologist, cardiologist, researcher, trainee, or allied health professional, EP Edge Journal Watch brings you the signal not the noise. Expect sharp summaries, thoughtful commentary, and practical takeaways designed for the busy clinician who wants to stay ahead of the curve
Welcome to epedge in collaboration with Heart Rhythm Society's digital education. I'm Mike Lloyd, and with us as always is doctor Niraj Sharma who's going to discuss a variety of articles, that's come out in this last month or last few months that we may have missed. Daraj, thank you as always.
Dr Niraj Sharma:Thank you, Mike. I appreciate it, and, welcome to another issue, another edition of epedge with, HRS. Mike, we have, we have three studies to go through. There were actually a lot of studies that, came out over the last, three or four weeks in the, Journal Watch newsletter. Three studies that we have chosen, are the PIFPAF study, then the, HIS alternative two study, and the last study is the AF density and ischemic stroke risk.
Dr Michael Llyod:I love this I love this potpourri you have for us. I mean, it's JAMA, something that's not in my rotation, and then you have one in Jack EP and then one in European Heart Journal. So these are good things that a lot of us may have, overlooked. So let's start with PIFPAF.
Dr Niraj Sharma:So PIFPAF came out in Journal of Medical... Sorry, Journal of American Medical Association, JAMA, in August '26, a couple of months ago. In the same issue, there was another trial, the IDEAL AF trial, which kind of looked at similar population persistent AFPs. So maybe we'll touch on that a little bit, but let's focus on our trial here, the PIFPAF PAF trial. This came out, in JAMA, August 2026.
Dr Niraj Sharma:So the full name of the paper is Pulmonary Vein Isolation Using Pulse Field Ablation with and without posterior wall isolation in patients with symptomatic persistent atrial fibrillation, and, then it goes on to say the PIFPAF PFA randomized clinical trial. The principal author was Laurent Roten and the senior contributors were Tobias Reichlin, Peter Joyn, and Patrick Baxter. This trial was carried out predominantly in six Swiss centers. The background here again is we've been doing pulmonary vein isolation, and it's pretty much the gold standard for paroxysmal AFib, and also for persistent, but in persistent, what do we do beyond the pulmonary veins and the conventional approach has been to target the left atrial posterior wall. So, with that in mind, does this additional strategy make any difference?
Dr Niraj Sharma:There have been numerous other trials that have been presented, published, predominantly with RF, and there has been a few with PFA, but nothing like this in a randomized situation whether you do PVI or PVI plus posterior wall. So, the design was an investigator initiated randomized open label multicenter superiority trial, blinded endpoints and education. The patients, that were enrolled were two zero six undergoing first left atrial ablation for symptomatic persistent AF, one hundred and two patients in the PVI plus posterior wall, and one hundred and four in PVI alone. The key exclusions were prior left atrial ablations, persistent AF more than three years and LA diameter more than six centimeters, Presence of intracardiac thrombus and contraindications to anticoagulation. The randomization was a one to one after left atrial voltage mapping stratified by center and posterior wall scar.
Dr Niraj Sharma:Energy strategy was a single PFA platform, which was the pentaspline catheter was used. PVI in both groups, overlapping flower configuration, applications to each posterior wall, isolation in the intervention arm. Monitoring, this is interesting, they used the loop recorder, implantable loop recorder was done and, this is very important, which as we'll discuss, placed at the end of the procedure or within one day, and then there was a centralized assessment. The primary endpoint after the, three month blanking was first AF or organized atrial tachyarrhythmia greater than or equal to or greater than thirty seconds during days ninety one to three sixty five. Secondary outcomes were AF burden and sustained episodes, cardioversions, repeat ablations, antiarrhythmic drug use, hospitalization, and quality of life and safety.
Dr Niraj Sharma:The power that they use again, which would become more important as we discussed, was an 80% power for an ambitious 20 absolute recurrence reduction from sixty percent to forty percent at follow-up in twelve months. So that was the that was the background. Jumping to the results and what the statistics actually show. The primary recurrence, that's after the blanking ninety one to three sixty five days, the posterior wall plus PVI was fifty point six percent and PVI alone, this is the recurrence rate, was sixty percent. So, percent recurrence with PVI alone and fifty point six percent with PVI plus posterior wall.
Dr Niraj Sharma:So, this did not meet their superiority criteria. The mean AFAT burden was six point nine percent in PVI plus posterior wall versus eleven percent in the posterior, sorry with the PVI alone. So there is a four point one percent reduction. Recurrence lasting for more than one day was nine point nine percent versus twenty four point three percent. So, this is a significant difference if you looked at just recurrence equal to more than one day, nine point nine versus twenty four percent.
Dr Niraj Sharma:Repeat ablations are ten percent in the PVI plus posterior wall versus eleven point seven percent in PVI alone. Procedure time, as you would expect, slightly more, about twelve minutes more, eighty four minutes for posterior wall plus PVI, and, seventy six minutes for PVI alone. The ninety day safety, two percent in PVI plus posterior wall and zero in PVI alone. Of course, not not significant here. So that that were the...
Dr Niraj Sharma:That was the results here, Mike.
Dr Michael Llyod:I'm looking at these curves, Niraj. I mean, they're all clearly separated, and, I mean, I realized not... The primary was not significant, but this power that you mentioned to be able to detect a 20%. If I look at these curves, I instantly think underpowering because the... All of the curves, even the subgroups are all disparate favoring PVI with posterior wall in this persistent group.
Dr Michael Llyod:And maybe 20% is asking too much. I mean, if you can do 10% better
Dr Niraj Sharma:Yeah.
Dr Michael Llyod:Maybe that's important.
Dr Niraj Sharma:Agree with you. I agree with you a 100%. I think 20% was very ambitious, and I think that led to... Not only was it too ambitious, I think the monitoring... As you mentioned, the curves are are diverging, and maybe a longer duration, maybe a follow-up of eighteen months, maybe the curves would have displayed more separation.
Dr Niraj Sharma:Yeah. I think I think that was one of the issues. The the other issue is what... This this trend that we're having now of trials, our AFib ablation trials, kind of moving away from that thirty second mark. You know, we had the event guard Right.
Dr Niraj Sharma:Which kind of did things a little bit different. They did look at the thirty seconds, but the asymptomatic, they said, well, we'll look at one hour, one hour of AFib. Here, they did look at that, one day recurrence lasting for greater... Equal to a greater than one day, that was a significant difference. Although it was a secondary endpoint, I thought the Right.
Dr Niraj Sharma:This is this is important to look at. Do we... You know, I mean, what is clinically meaningful? Thirty seconds? Is that meaningful or or or not?
Dr Niraj Sharma:What are your thoughts on that?
Dr Michael Llyod:I I I agree with you. I mean, it's important to detect everything, and so I think the bar was set very high to detect any recurrence, which is something. But for a patient, I could handle ten seconds or thirty seconds, but for six hours, that would be another story. That might be life disrupting. I really like these authors dividing it, that duration threshold in figure three where they divide...
Dr Michael Llyod:Okay. What if we look at durations of greater than one hour? Well, then PVI with posterior wall wins.
Dr Niraj Sharma:Clearly. Yeah.
Dr Michael Llyod:And then what if we look at duration threshold greater than one day? PVI with posterior wall wins. It's a significant difference. So I like that they they mixed up the thresholds. You know, I think I...
Dr Michael Llyod:I'm glad you discussed this one, Niraj, because I worry that people are gonna read this and say, oh, posterior wall, it doesn't matter. This is just yet another nail in the coffin of posterior wall isolation. But if you look into the... This data that they present, I think it tells a very different story.
Dr Niraj Sharma:It really does, and I appreciate you pointing out that table that they have. The difference is huge, you know, when you look at greater than six. It's across the board, if you look at that table. What is your approach for posterior wall? In this study, they didn't take long standing persistent AF and large atria.
Dr Niraj Sharma:So let's just go by what the trial actually studied. Do you do you... And for persistence, do you map out the posterior wall, and do you... Irrespective of low voltage or or not, do you just go for it, go for the posterior wall, or do you say, well, the posterior wall looks healthy. Shall I just let it be?
Dr Niraj Sharma:Because it could be... You know, ablation can be arrhythmic, proarrhythmic. So should I ablate less and see and then come back if there's a recurrence?
Dr Michael Llyod:With this pentaspline technology, Niraj, I'm... My threshold to ablate the posterior wall in a persistent has gone way down. I I admit. I drank the Kool Aid. I, you know, I think that this is embryologically the same tissue that the pulmonary veins come from, and so I am much more likely just to do it.
Dr Michael Llyod:It takes... I think maybe because it's quicker. I realize and I admit wholeheartedly that I don't have a lot of data, to support that, but that's sort of my approach. For proximal, I would not ablate the posterior wall unless I saw low voltage. Or in this technology, if I make such a narrow isthmus that I'm worried about a flutter, then I'll...
Dr Michael Llyod:Then I feel like I have to bridge that, get rid of that isthmus if it's a tiny little atrium. What are you doing?
Dr Niraj Sharma:Yeah. What I do is I look at... To see if the tissue is healthy or not. So I map in sinus rhythm, and I... If it looks healthy, I let it be.
Dr Niraj Sharma:But you're right. It's Yeah. One of the things I struggle with, and just like you, is I'm there. Right? And it's so easy to do.
Dr Niraj Sharma:Why not just do it? Right? And, you know, in this in the same journal, JAMA, same, month, there was this ideal AF trial that that looked at, low voltage, and then they looked at the usual conventional equal to a less than 0.5 millivolt. And then they they mapped out... If it was more than three centimeter square area with that low voltage, they found going after that had a better result than than healthy tissue.
Dr Niraj Sharma:But
Dr Michael Llyod:So the the punch line for our listeners, Niraj, for the the sister trial that was in that same journal for the ideal AFib trial was ablate if you see that low voltage.
Dr Niraj Sharma:Yeah. It supports targeted ablation. Yeah.
Dr Michael Llyod:Yeah. So Well, we better move on to, the Jackie p article. Michael Vinther's primary author direct his left bundle branch pacing as an alternative to By V pacing in patients with HFrEF and a typical left bundle branch block.
Dr Niraj Sharma:Right. So this is this is our conventional patient that would meet the criteria for a BI V device. And this, again, as you mentioned, came out in August at... In Jack ep. The main...
Dr Niraj Sharma:The primary author was Michael Winter. Alright. This this trial was carried out in two centers, in Denmark and the other one was in The United Kingdom. What they did was they... This was a prospective two center randomized non inferiority trial.
Dr Niraj Sharma:Patients were blinded to which device or which modality they got and the core laboratory was masked as well. The population that was studied were 150 symptomatic heart failure reduced EF patients with typical left bundle branch block and out of the one hundred fifty, two withdrew before implantation. It was a one to two randomization in favor of CSP, so one for By for every two CSP. Initially, we'll talk about this, the initial randomization was 49 for by v, and you would expect a 100. So 99 for, the CSP pacing, but there was a lot of patients that moved from, one to the other.
Dr Niraj Sharma:The intervention was His pacing with bundle correction when feasible. Otherwise, left bundle branch area pacing. The comparator was the coronary sinus lead based conventional IV CRT. Primary endpoint, relative percent change in left ventricular end systolic volume at six months. It was a non inferiority margin and the margin they chose was minus 10% points and it was intention to treat primary analysis.
Dr Niraj Sharma:Secondary endpoints were left ventricular ejection fraction, QRS duration, NT proBNP symptoms, six minute walk, capture thresholds and device implant measures. Crossover was permitted. Let's talk about the crossover part. So as you know, the
Dr Michael Llyod:15%.
Dr Niraj Sharma:15%, crossed over to the the IV arm. So So a lot of them... And then I think one moved the other way from Bi V to conduction system pacing.
Dr Michael Llyod:I think, Neeraj, before we leave that point, I think that's an important nuance to this paper. You know, is very similar to the Brazilian paper, which was, of course, a negative trial. Think you discussed that this, maybe on this podcast, but the crossover was higher from, so people getting CSP, the crossover rate was higher to go on to just say, forget it. Let's do by VCRT, which maybe says these, researchers were really trying to get true conduction system pacing, and if they couldn't, if they failed, then they went ahead and did the the LV. And the crossover rate the opposite way was only two percent.
Dr Michael Llyod:So maybe these CSP patients, unlike the Brazilian trial, are true or are much higher, His selective... Or, left bundle selective pacing.
Dr Niraj Sharma:What happened in this trial was the criteria that we used for conduction system pacing were an evolution then, and they they really didn't have strict criteria. And I think in 2023 is when the Europeans came out with their statement about what the criteria should be. And what these folks did was they went back and evaluated all their conduction system pacing, and they found that ninety one percent of their conduction system pacing patients actually met the current twenty twenty two, twenty three criteria, and only five percent had deep septal pacing. So they did a really good job, making sure that, in retrospect at least, that there was good conduction system pacing. Alright, so the results.
Dr Niraj Sharma:So the main, the primary endpoint was left ventricular and systolic volume, and it was pretty similar for conduction system pacing, there was a 35% reduction, and in BI V, it was a 34 plus minus 22%, reduction as well. So, it met the non inferiority, criteria. They of course ran statistical analysis for superiority and that did not pan out. So really, am going to stop there for a second. Looks like based on this trial, both both are...
Dr Niraj Sharma:I don't know what we should call it equivalent or not, but they're both, well, they're both non inferior, one one versus the other.
Dr Michael Llyod:I think that's that's the the take home that I'm getting from this. I think they did it carefully. The weight of the body of evidence so far, I believe, in a classic left bundle HFrEF population is that either can achieve, but it has to be a classic left bundle, and it has to be very carefully done CSP. But this is also a cost issue, and there's another trial coming from Russia. I mean, this is what compelled the Brazilian, which I think the funding agency was government.
Dr Michael Llyod:So now if we have a technology that affords us CSP without, adding extra leads, you know, I'm thinking about the the low profile defibrillator leads that can achieve CSP. This is a big, cost advantage.
Dr Niraj Sharma:Right? I would think so. I I really would think that this may... I mean, at this point, since we don't have major large randomized trials, we have a lot of random, except for that sync CSP trial, the Brazilian trial that turned out to be, actually turned out to be worse, CSP turned out to be worse than By V. All the other trials, point towards the direction that that this is non inferior.
Dr Niraj Sharma:The way I look at it until we have a much larger randomized trial is is try by v in this classic situation, left bundle reduced ejection fraction. And if the anatomy, the CS anatomy is poor, then just jump straight. Not even try putting a CS lead in because the anatomy is so bad. You just go and Mhmm. Put a CSP in.
Dr Niraj Sharma:That's that's my take here. The
Dr Michael Llyod:bailout the bailout approach, and I think that's a... That's valid. I mean, the one other thing I've seen a lot is is why not just... If you have the ability to put in a CRT, with the conduction system with the fibrillation capability, defibrillator, integrated, why not just try both? And you can turn off one or the other.
Dr Michael Llyod:Mhmm. So sort of do the lot CRT approach as well. Yeah. But I I... I'm with you.
Dr Michael Llyod:I think there's nothing that replaces CRT in a classic left bundle HFrEF. I mean, the the the the data is out there. You cannot refute it. There's mortality benefit for that. Right.
Dr Niraj Sharma:Yeah.
Dr Michael Llyod:But this is really yet another signal that CSP is probably gonna be equivalent.
Dr Niraj Sharma:I guess before we end this trial, yeah, quick point to what you you mentioned, we need we need, this is echo data, and, you know, the primary endpoint was echo. They did have secondary endpoints in terms of quality of life, six minutes, etcetera, but we'd need mortality data, before before I think it becomes, you know, the the to go procedure.
Dr Michael Llyod:Mhmm. Alright. Well, let's go to the European Heart Journal.
Dr Niraj Sharma:Okay. Last So this is our atrial fibrillation density and ischemic stroke risk. It was in the European Heart Journal and was published in March 2026. The title of the paper is Atrial Fibrillation Density as a Biomarker for Ischaemic Stroke Risk Reduction. The primary author is Lindsey Rosman and the senior author is Rod Passman.
Dr Niraj Sharma:The funding, there was no external funding for this specific analysis. There was an accompanying editorial that was published later on and then there was also some corrections that were made to the trial data. It was actually, I think it was more of a typo than actual problem with the data. The clinical background is, we know that atrial fibrillation burden, the higher the burden, the more chance you have of an ischemic stroke, but are all burdens the same? You know, for example, is ten percent burden in two patients the same if they're having short sporadic bursts of AFib versus a patient who's in AFib, you know, a lot of the time, versus small bursts.
Dr Niraj Sharma:Does duration or the density make any difference was the thought process here. This was, yeah.
Dr Michael Llyod:So, Niraj, can I? Let's pause just for the listeners because this is... It can it can be confusing when we say density and burden, but what they're saying is over a month, if somebody can have ten hours of A fib over a month, ten hours is the burden. But the density is lower in someone that has that ten hours in little little snippets of minutes or seconds throughout the day and the density is high in the same burden if all of that a... All of that ten hours occurred in one long epoch.
Dr Niraj Sharma:That's correct. Yeah.
Dr Michael Llyod:Is that right?
Dr Niraj Sharma:That's exactly right, miss. Yes. That's exactly right. And what they did was they they looked at a mathematical model that they created.
Dr Michael Llyod:Okay.
Dr Niraj Sharma:And they they looked at what what the spread... Like you said, what the spread would be if spread of the density would be if it was spread out during the whole month. So you normalized the spread, and then they used a mathematical equation to come up with a density between zero and one. That's, that's how they did it. They didn't really, you know, plot how many episodes you'll have in a certain minute or a certain duration.
Dr Niraj Sharma:It was a thirty day window. You normalize it, and then you looked at the spread of these episodes during that window. So it was a it was a complex formula that they used to come up with the zero to one density equation. So, the design was a multi center, respiratory observational analysis. They used device determined atrial fibrillation episodes and then they looked at strokes looking at the electronic health records.
Dr Niraj Sharma:So, they did electronic assessment through their devices and then they went back to their medical records to assess the actual stroke risk. The sources were the Veterans Administration Registry and the University of North Carolina Device Surveillance Registry. They screened 41,780 patients and they captured 12,868 patients with these two databases that they had. The risk profile, the mean age was 72, the CHARDS BASC score was four and the median follow-up was for four years. They had to have at least one day with greater than or equal to six minutes of device related AF, excluded permanent AF and inadequate atrial sensing.
Dr Niraj Sharma:The AF burden was the fraction of the monitored time in AF during each thirty day window. The AF density was the clustering score between zero to one. So zero distributed to one consolidated measured per ten day interval. The primary outcome was first ischemic stroke and adjustment was using this parametric G formula with time varying covariates and competing non stroke death separate cohorts pooled by random effects. The key caveats were AF detection was not manually adjusted and there was an incomplete recording partly imputed.
Dr Niraj Sharma:So the results, the way they did this again was the density category low, was one. That was the reference. Medium, 1.24, medium to high, 1.5, and high, 1.75. Then of course they did some corrections because of the typo that occurred. Basically, the cross classification suggested that low burden, high density could be associated with greater ischemic stroke risk than a high burden, low density.
Dr Niraj Sharma:So, were the two, that was the main, I guess the result that came out here was a a low burden with high density has a higher risk than a high burden with low density.
Dr Michael Llyod:How do you reconcile that?
Dr Niraj Sharma:Yeah. So it's what they're saying is that density or clustering, meaning a long, I guess, a longer duration, would be higher
Dr Michael Llyod:Is just more important.
Dr Niraj Sharma:Is just more important. Higher, I guess the duration, the higher the duration, the more there is risk of stroke. So lower Yeah.
Dr Michael Llyod:Mean, I think
Dr Niraj Sharma:Go ahead. Yeah.
Dr Michael Llyod:I I think this sort of I mean I'm looking at the figure and the main figure here in Table two. I mean the discriminating power of the density looks really good, right?
Dr Niraj Sharma:Does.
Dr Michael Llyod:For stroke, I mean, for stroke and all these and, you know, even for all of these outcomes, I mean, the discrimination power looks better than than burden for sure. So should we start thinking about just whether or not you have more than, you know, x amount, x duration epoch rather than how much percentage?
Dr Niraj Sharma:Yeah. You know, I think this study probably will lay a groundwork for a larger trial. Because of course this was all device related and we know that the device related population may be a different clientele than our conventional, hence, you know, our criteria is a little bit different as to when you anticoagulate our device related AF patients. And this was a, you know, observational trial, so we don't really know in a randomized prospective follow-up whether this would actually be true. I think this is definitely hypothesis generating, but, I think more studies would need to be done.
Dr Michael Llyod:I think that doctor Passman's REACT trial, which is monitoring, will be able to get more information on just the general population at large without implantable devices, and we'll see what the wearable... If the wearable burden versus density argument is the same.
Dr Niraj Sharma:Look. Actually, good that you pointed that. I'm really looking forward to that trial because this this really to me was an eye eye opening trial, extremely well done, and I think it lays the groundwork for a larger clinically based prospective trial.
Dr Michael Llyod:After I've read this, Niraj, I I've thought about clinical impacts and how often sometimes I'll say, oh, your pacemaker only says it's less than 1%. And, you know, that's great. Congratulations. But what I need to start really paying attention to is how long... How was that 1%?
Dr Michael Llyod:Was it because he had twelve hours in a given month, or was it just that he had five minutes, you know, spread across... Sprinkled across the month? Because it seems like this is telling us that that five hour epoch is way more important with respect to stroke risk.
Dr Niraj Sharma:Exactly. I think, yeah, no, I think whether right now based on this trial, whether that's enough for us to say, you know, we should stop anticoagulation or not. It's not there yet. But Yeah. Yeah.
Dr Niraj Sharma:I think we'll just wait and see. But I think this was a really groundbreaking foundational trial.
Dr Michael Llyod:I'd say that all the papers you picked this week, Niraj, are... Have been really, really important and thought provoking, and I wanna thank you as always and encourage our listeners to check these articles out even if they may not be in journals that you normally have in your rotation.
Dr Niraj Sharma:Great. Yeah. I I would agree with that a 100%, Mike. Couple of announcements before we close. Our podcast achieved a landmark one year anniversary, epedge journal watch podcast, and we've had more than 10,000 downloads, more than 3,000 subscribers.
Dr Niraj Sharma:And, another big announcement next month, November, would be our first, inaugural recording with the Latin American Heart Rhythm Society. Looking forward to that and, subsequent, translated versions of our podcast to follow.
Dr Michael Llyod:Congratulations, Niraj. You've been listening to epedge collaborating with HRS.
Dr Niraj Sharma:Thank you all. Bye.