Dr Michael Llyod: Welcome everyone to the Heart Rhythm Society's monthly wrap up in collaboration with the EP Edge. This is keeping you informed with our field's latest science. Joining me this morning is doctor Niraj Sharma, creator of EP Edge. Niraj, welcome, and thank you again for this important collaboration.
Dr Niraj Sharma: Thank you, Mike. Pleasure to be here again. This is our second issue, of this collaborative effort that HRS and, EP Edge Journal Watch is doing together. Doctor
Dr Michael Llyod: Sharma has has distilled a a bunch of recent stuff, and, it's it's good to have a human brain kind of, pick and choose this this, very interesting potpourri. We got a lot to get through. So let's let's jump into it. The InEurHeart trial. This is a European Heart Journal, trial, Niraj.
Admittedly, this is not usually on my rotation, so kudos to to look and find this. A great trial, looking at AI and VT. What's it all about?
Dr Niraj Sharma: Right. So yeah. You know, we actually have two randomized trials to talk about today. InEurHeart, we're gonna go first and then followed by the OPINION trial. But a little step back, just to kinda give you a perspective of what EP Journal Watch did over the last five issues, we actually analyzed 49 trials.
And out of those 49 trials, seven were randomized. And the others were like a potpourri of observational data or meta analysis or translational research. So out of the 49 trials, seven were randomized. Out of those seven, we chose these two because I think they have some sort of a practical input as to what we do and what's the the the future holds. InEurHeart, I think is probably, in my opinion, one of the better randomized trials that came out over the last month or two months.
What what was this InEurHeart trial? So this was a a trial that was published February 2026 in the European Heart Journal. The the the trial is actually a CT guided versus conventional catheter ablation for ventricular tachycardia. And the more I read into this trial, the more relevant it becomes with our current state of affairs as we move from more, I guess, less electrophysiology, more anatomical ablation, similar to what we 've all seen with pulse field ablation. But this is kind of similar along those lines where we're kind of moving away from electrophysiology and moving more towards anatomically guided ablation.
But okay. So this trial was investigator initiated trial, multicenter, open label, and it was a one to one randomization for superiority. And the the key point here is, you know, the the the usual trials we have is superiority in terms of efficacy, but this trial, the superiority was for procedure time. So this was a European trial, 14 centers in four countries. They enrolled a 113 patients with prior myocardial infarction and significant VT.
Let me tell you how they quantified a significant VT. Equal to a more than three VT episodes treated with the ATP, greater than one one or more appropriate AICD shock, sustained VT below the ICD detection rate documented by ECG or monitor, and sustained VT on a twelve lead EKG in the absence of an ICD. So those were the inclusion criteria. Pretty pretty robust inclusion criteria. And there were two important exclusion criteria.
So patients should not have had a prior VT ablation, and the other one was a significant contrast allergy. The other ones were were actually common sense stuff. If you had an LV thrombus or a mechanical valve, if you had polymorphic VT or VF, they they were all excluded. A recent acute coronary syndrome within thirty days also warranted exclusion along with active ischemia. So this was the this was the inclusion and exclusion criteria.
The the trial major hub was the CHU Bordeaux group. They had funding from CIT. I'm not really familiar with that. Health grant from EU and the French ANR grant. And the although these were the funders, they had no role in the design conduct analysis or the decision to publish.
So they were pretty much hands off. We can talk about disclosures at some point later on, but let's just keep on going with the trial. So what they did was they enrolled a 113 patients, predominantly men, ninety one percent. Injection fraction mean was about thirty five percent. And about interestingly, about thirty nine percent had a history of electrical storm.
About forty three percent roughly were on amiodarone. Okay. Men predominated women were only eight point eight percent. So that's probably one of the limiting factors of this trial. They did a one to one randomization.
Once they were randomized, pre randomization, they had a CT scan done. So the the thought was, well, we have to do a CT scan essentially to rule out a LV thrombus. CT scan was just by a conventional scanner. There was nothing sophisticated about the CT scanner itself, but the the way the contrast was given was in a in a biphasic fashion to image both the LV and the RV together. So there was a certain protocol that they followed, a rapid injection followed by a slower infusion.
So there was a special protocol for contrast. Once the images were obtained, they used this proprietary software called InHEART. And what the InHEART software did, it helped with segmentation of the CT images. The actual assessment of the images were done by two very experienced, more than ten years experienced physicians who were capable of looking at CT scans. So the InEurHeart software did help with segmentation, but did not come up with an actual interpretation of the CT scan.
So that's how the trial was done.
Dr Michael Llyod: And so they they randomized one to one people that got this imaging guided, the the the AI based, software. What was what was the the time reduction? How much time did this save?
Dr Niraj Sharma: So where does the time saving come from? Right? You would think, well, the time saving came from maybe reduced ablation time, or was it the mapping time? So really, it just came came from mapping. In the in the CT guided arm, there was no use of high density mapping catheter, so maybe a cost saving effect there.
There was no mapping involved. They went straight with the anatomic interpretation of the isthmus. The isthmus itself was was the way they defined it was was an area of myocardial thickness within a thin area. So thin meaning scar, and then you've got these tracks or channels, which are thicker than the than than the scar area. So those were the areas that they were focusing on ablating.
So the reduction in time was more to do with no mapping and less to do with the abl in fact, there was more ablation carried out in the CT arm. The time for RF ablation was more in the in the the CT arm.
Dr Michael Llyod: Got it. And the outcomes so if we just take the mapping out of the equation, use this use this in heart software, you know, I worry about are they gonna really they're just blindly anatomically following something. Is is it gonna work as well as as what we're used to? But they found no difference in outcomes. Right?
Dr Niraj Sharma: CT guided arm, they still had inducible VT in twenty five percent. So they had to switch over in those twenty five percent to to a, you know, conventional approach.
Dr Michael Llyod: And I think we need to to mention that I mean, the harsh reality is, Niraj, I don't know about your lab, but that the this is our worst procedure. Let's face it. A VT ablation has perhaps our our highest recurrence rates, our worst outcomes, and our lowest success rates of anything we do. So it's to see some different strategy to to approach this. As you mentioned, we we we should disclose that some of the authors had financial interest in in in this, this, experimental arm, which may introduce bias.
But, I mean, let's face it. The decision to do VT, a lot of it has to do with how long these things take.
Dr Niraj Sharma: Right.
Dr Michael Llyod: So what how how long how long was the one versus the other?
Dr Niraj Sharma: Right. So in the intention to treat arm, in the CT guided arm, it took a hundred and twenty minutes, So about two hours. And in the conventional arm, their usual three d mapping, etcetera, it was approximately a hundred and fifty minutes. So so to be exact, it was a hundred and forty nine minutes. So, you know, so and this is on the intention to treat.
But if you look at per protocol, it was a 107 in the CT guided and hundred and forty nine in the conventional. So in the first in the in in the intention to treat, it was a 19% reduction in time. And in the per protocol, it was a 28%. So I think when you look at timing, you're right. You know, currently, VT ablation can can go on for hours.
Right? And and then you've got a sick patient as well. And then if you're doing the conventional approach, they might be you you might be inducing VT, and then the hemodynamic instability that goes with that. So there there's big pros for having an anatomical approach, at least first, to guide you. And if it's successful, no further induction, then that's it.
And then if it there if there is, then you can switch over to your conventional arm. So
Dr Michael Llyod: So when this comes out commercially available, you're gonna put it in your lab?
Dr Niraj Sharma: I think so. I think so. I think it would be it would be it won't be across the board, but Right. It would be for people or patients that are hemodynamic beyond stable. And I gotta point this out that the the trial included, of course, just ischemic cardiomyopathy or ischemic VT.
This does not apply to our non ischemic population. So yeah. And you did mention about the disclosure. Of course, you know, disclosure are important. Some of the authors actually had had shares in the InHeart organization.
So you just have to keep that in the back of your mind when you look at this trial.
Dr Michael Llyod: So this is the InEurHeart trial European Heart Journal. Niraj, thanks for picking this one out. Let's talk about the other randomized trial, that, EP Edge chose, the OPINION trial. Again, European Heart Journal, valve patients randomized to left atrial surgical closure during their surgery or not. Pretty straightforward.
Yeah. Tell us about this trial.
Dr Niraj Sharma: So so this trial was initially presented at the European Society of Cardiology meeting in Madrid, August of last year, but just published in the same journal, European Heart Journal, in May of this year. The thought I believe in this trial was, why don't we take patients who do not have Afib, but have structural changes that would predispose them to Afib, and then proactively take care of the appendage? So that was the the thought and the concept. We know patients who have significant bowel disease, significant left atrial enlargement, that they that they are at high risk for both AFib in the future and also post op AFib. The OPINION trial was a Chinese trial.
There were three centers in Beijing, China, but only one of the three centers did majority of the enrollment and procedures. The other two were really minor players. So the in in the in the trial, they enrolled a huge number of patients, more than 2,000 patients, and it was a one to one randomization. So roughly a thousand patient in in each of the arms. The arms were, you know, conventional valve surgery.
The valve surgery was aortic and mitral. And about twenty five percent of patients who went for valve surgery also had bypass surgery carried out. So it wasn't a pure pure mix. So it's a one to one randomization. Majority of patients, again, here, Mike, got mechanical valves.
So that's another confounding factor that we'll talk about, mechanical valves, and they were put on warfarin. So there was a one to one randomization. The patients that were randomized to left atrial appendage exclusion had the occlusion carried out with an amputation. So they it was a standard protocol. There's a
Dr Michael Llyod: great video on that too. If you
Dr Niraj Sharma: Yeah.
Dr Michael Llyod: If you click on that link, they show a nice closure.
Dr Niraj Sharma: Right. So yeah. So yeah. Actually, they do actually, and they actually talk about the stump, etcetera. So the primary endpoint of this trial was ischemic stroke.
Didn't really look at atrial fibrillation burden, etcetera.
Dr Michael Llyod: The I think the important characteristic that I found in the supplements is fifty, about fifty percent of these patients were on on on warfarin. I mean, a lot of them were on lifelong warfarin. So the question is, why why would you wanna close the appendage if they have to be on warfarin anyway?
Dr Niraj Sharma: I know. That was a a a big, big confounding factor in this trial. So that's yeah. It really does change your outcomes based on on the fact that they were already on warfarin. And another interesting tidbit was when they did the statistical analysis, they felt that there would be a forty percent reduction in ischemic strokes if you had a left atrial appendage occlusion carried out, which was was, I thought, a very high number.
And I and then based on the the episodes that occurred, which was only seventeen percent, this trial too was underpowered to look at that difference. There was another another big limitation of this trial. But nonetheless, the trial showed that there was no difference between the two arms.
Dr Michael Llyod: So another neutral, trial for surgical left atrial appendage ligation. Do you feel like there's a role? Are you telling your surgeons based on what we have thus far, the sum of the data? Should we be asking our surgeons to to snip off the appendage?
Dr Niraj Sharma: Yeah. You know, snipping of the appendage doesn't really add much time to the procedure. So and, you know, with minimal complication risk. Now I know the appendage does have biochemical and electrophysiological properties and mechanical too. So taking off an appendage without really solid background, I think at this point, it's inconclusive that we should suggest that.
And particularly in the patients who don't have if if if they do, it's it's they should. But if they don't, I think it's still at this point inconclusive. And even prior to the OPINION trial, there were question two or three other trials that were done. That too was the results were not conclusive. I think this this trial doesn't really add much to to what we already have.
Dr Michael Llyod: But it is very large, very randomized, 98% follow-up. So I think it it's sort of the the neutral nail in the coffin for this in terms of all comers, and maybe we should be more selective
Dr Niraj Sharma: Right.
Dr Michael Llyod: In who we ask or in who we subject this to.
Dr Niraj Sharma: Right. Right. Great trials. Yeah. There's one more point I wanna make, though.
There is a trial that we should be looking out for. It's called the LEAPS trial, l e a a p s. And this trial is much, much larger. It's using the the clip. And it's it's the follow-up is much longer as well for five years.
So I think that trial should be a trial that hopefully would all put all this to rest in patients who don't have established AF.
Dr Michael Llyod: The LEAPS trial. I'll look out for it. Yeah. Wonderful randomized trials. Journals, again, not on our rotations usually.
Niraj, you ready for rapid fire? Yep. I am ready.
Dr Niraj Sharma: So Okay. What what do we have for rapid fire?
Dr Michael Llyod: Cavioli. What in the heck is a ravioli? It's not a ravioli. Cavioli in the sinus node, Jacky p. What's this all about?
Dr Niraj Sharma: So this is one of our translational papers, and I and I I too had never heard of what Caveolae is. I had to kinda do a little bit of reading on on this, but it's a really, really good trial. And I thought it's it'll be good for for us all to know about how deep electrophysiology is going into cellular structure. So so Caveolae, what is a Caveolae? So Caveolae are these minor nano indentations in the plasma membrane.
And this is where we have our molecular clocks, the calcium clock and the membrane clock. And we know that disruptions in these clocks within the sinus node can cause issues. But what they found in this trial was if you have a certain degree of separation of the Caveolae within the membrane between the the the calcium clock and the membrane clock, this seems to disrupt normal sinus node function. So what they did was they took out these these mice, knockout mice, and they they caused this Caveolae three mutes mutation to occur. Now what is Caveolae three?
This is responsible for setting up the scaffold of these these indentations to occur. So when you take the scaffold away, separation occurs between the membrane and the calcium clock. So what they found was when you separate these small distances, there occurs a dysfunction in the sinus node. And they actually looked at the same model in patients who had heart failure, and they found similar results. So so when you knock out the scaffolding of these caveolae and you have separation between the two clocks, it itself can result in dysfunction of the sinus node.
Dr Michael Llyod: Okay. So it's not it's not just a matter of fibrosis or cell channel down down regulation. This is a a microarchitectural problem that may account for sinus node dysfunction, and it certainly taught at least me a a new new term.
Dr Niraj Sharma: Right. And there's also a rare entity that that we we carry as, you know, humans. They're not talking about mice here. It's the Cav three mutation. I didn't realize it existed, but it does exist and it affects the scaffold.
And an interesting thing is that patients who have this mutation, they tend to die in their sleep because of profound bradycardia. Interesting. Yeah. So I didn't realize there was a mutation.
Dr Michael Llyod: Is that in a gene test, or is that something is that in, like, an arrhythmia panel?
Dr Niraj Sharma: I'm not sure about whether it's in our arrhythmia panel, but it's definitely a mutation that's tested for.
Dr Michael Llyod: Okay. Rapid fire number two. Alcohol consumption and incident A fib meta analysis, Europace. What do we know?
Dr Niraj Sharma: Right. So this is a trial that just came out in Europace, and it came out from Prash Sanders group. And it's a really, really interesting meta analysis. They actually took 26 observational studies and with nearly 15,000,000 people. So a really large scale analysis.
And, you know, what what they found in this analysis was was a little bit disruptive, and we'll talk about that in a second. But what they did in this trial was they they quantified alcohol consumption into different groups. And then they compared those groups with people who who didn't drink. Now again, remember, this is observational data. So they compared people in in these trials that didn't drink versus different stratification.
And they what they found was not a linear relationship. This is one of the big things that came in my mind. The way alcohol stood was if you had a small amount, it really didn't do anything. And then as you progressively drank more, there would be a linear relationship.
Dr Michael Llyod: But Right.
Dr Niraj Sharma: They found it was a j curve. So if you if you were drinking less than 12 grams of alcohol, which equates to about a drink or so, it may have actually reduced your incidence of A fib. So that was one of the
Dr Michael Llyod: one one shot of tequila, 14 of alcohol, to put it in perspective. So one shot a night might reduce incident A fib.
Dr Niraj Sharma: Well, that's what this observational data suggested. So we talk about what are the problems with this. And then when you went to between twelve and forty eight, it suggested that it may may actually be helpful. Between forty eight and sixty, it was a wash. But if you had more than 60 grams, it clearly suggested that you you were prone to develop atrial fibrillation.
Dr Michael Llyod: So a clear uptick at that threshold of sixty grams, four or five shots, four or five drinks a night. That's a lot even for for Yeah. We here in The US. Right. But but, Niraj, you're saying that this analysis, which has some really nice statistical, advantages as well, you're saying that that moderate alcohol may not increase out A fib like we we always think about.
Dr Niraj Sharma: Yeah. It may not. It may not. But there's there's a few limitations that we need to talk about. So the reference group, which is the abstainer group, may actually be dragging the the risk to a different level.
Maybe, you know, maybe these abstainers are former drinkers. Maybe they are sick quitters. Maybe they drank and now they're sick and they're not drinking anymore. And maybe they stopped because, you know, they felt sick or there may be some mitigating factor that that actually caused them to to stop drinking. And then then then then people who drink one drink a day may actually be healthy.
They may they may have one drink and then go for a walk. Right? So you gotta look at these drinkers. Is there like an obese diabetic hypertensive patient who's taking a drink a day, maybe that's not the right person that we should, you know, tell them to
Dr Michael Llyod: do. These All all of these covariates. You know? One someone that has a glass of wine at night, higher socioeconomic, better access to health care, maybe they exercise every day, etcetera, etcetera. Yeah.
Really cool. I I I'm still calling a win for someone that likes a glass of wine every now and then.
Dr Niraj Sharma: Yeah. I mean, I I I think it's if you're healthy, yes. I would say that. And I and I would, you know, still go with the current recommendations Right. Which is, you know, if you have A fib, three drinks a week, but best to eliminate it if you have established AF.
Dr Michael Llyod: Last trial. This is a brief communication for, regarding a pulse self exam for AF screening. Tell us about, this one, Niraj.
Dr Niraj Sharma: This is one of the trials that, we covered in, Journal Watch, and it's a it's actually a research letter. Usually, research letters don't really make it, but I thought this research letter needed to be discussed. It's a it's a it's a very nicely done randomized trial and very cheap. What they did was they they took patients who were at high risk for A fib, not established A fib, high risk for A fib. And they taught them by showing them a ninety second video of how to check your carotid pulse and how to check your radial pulse twice a day for at least two weeks.
And what they found was there was a nearly a double detection of atrial fibrillation. So Wow. They went from yeah. So in this group that was taught how to take their pulse, it was five point nine percent versus two point two percent. So it it it it really doubled the detection of A fib.
But there's also this this this bias called the ascertainment bias. If you tell the group that, listen, you gotta watch out for this problem and you're at high risk for developing versus a group that you don't, people that have been taught to check, they actually would be watching out for symptoms and checking their pulses more often than the other group. So that truly can be a factor. And then what they did was they they analyzed patients who had a smartwatch as well. And then they removed those people that had a smartwatch, and then the the sensitivity even got better.
Dr Michael Llyod: That's wonderful. Elegant in its simplicity. Ascertainment bias aside, you don't need an Apple Watch. I mean, I see global global health implications for this.
Dr Niraj Sharma: Yeah. I I I do too. I mean yeah. And, of course, this doesn't take away our, you know, our conventional monitoring that we do. But for a patient that does not have an A fib or even a person who's had an ablation, Right?
Has had an ablation and is not familiar with using you know, I mean, a lot of my patients I'm pretty sure, Mike, you have that as well. A lot of our patients do have a smartwatch, but they don't know how to use it. Right? They wear it, and you have to educate them about using a smartwatch. And a lot of them, of course, don't have a smartwatch.
So a quick little education about how to take your pulse could can go a long way.
Dr Michael Llyod: Well, as usual, doctor Sharma, I feel educated. I I I wanna thank you again for reviewing this in our monthly wrap up. And Niraj Sharma, quick chance for a plug for your EP Edge.
Dr Niraj Sharma: So thank you, Mike, and a pleasure again to be participating. Just a reminder, the EP Edge Journal Watch newsletter comes out every every week, and it's available on Substack, on LinkedIn, and it's accompanied by a podcast that goes over the same same information, but in, of course, in a audio format. So if you're driving and you don't have time to read, just listen to it on your commute, and we all have to commute a lot.
Dr Michael Llyod: Yeah. You've been listening to the Heart Rhythm Society's monthly wrap up in collaboration with the EP Edge. I'm Mike Lloyd for digital education, and we will see you next month. Thank you, Neeraj.
Dr Niraj Sharma: Alright. Take care, guys.