So it's my honor to introduce John Zapp, who's giving us an overview of what the studies say about VT ablation. I'm curious to hear what you picked, John. Please. Dr. Steven, Dr. DeGroote, thank you very much for the opportunity to speak here. I think we're underway. I've been asked to talk about the trials in VT ablation, and it's easy to do that. Here are, by the way, my disclosures again, but it's easy to do that because there aren't very many. So I'll tell you at the beginning what I'm going to end up saying by the end, which is first, that trials of catheter ablation of VT are really difficult to do. Second, VT ablation does work. And third, VT ablation is better than pickling your patients. But a lot of the details beyond that, we still have work to do. I come from the east coast of Canada. Once in a while, we get fog. You probably wouldn't believe it, but it happens. I'm, one of my favorite places is to be out on the water, but sometimes in the fog, it's concerning. And so this is a buoy or a marker in the water. I'll think of it like evidence. So we're trying to navigate our patients with lowest risk and best quality of life. So we need two things. We need evidence, like a buoy, to tell you there are rocks right over here. When you see a red buoy, it means you're supposed to go on the left side of it. But we also need context because if you're coming at this red buoy from the other side, you'll go right on the rocks, even though you go on the left side of it. So we need information and we need context. So first off, it is hard to complete clinical trials of ET ablation. I recently reviewed clinicaltrials.gov to see what trials were underway. Many trials have started, seemingly like the research projects I've started. We start many and only a few finish. And it's because it's so difficult to do, so difficult that Sanna Al-Khatib, after she wrapped up Calypso, put together a group to report, to write a paper on how hard it is to do the trials. Doing research on VT ablation, like doing research on any intervention, depends on having an effective mature intervention that you're testing. So one of the reasons that there are only a few trials in catheter ablation for VT, randomized trials, is because it's only been a mature technology for a relatively short period of time. So EP is young, VT ablation is younger. Really, we only started a modern era of VT ablation in the 2000s. And now that I think we've reached some plateauing of development of VT ablation, at least using a catheter and radiofrequency energy, it is time to have trials. So here are the clinical trials. The randomized clinical trials that have been completed. Obviously, there's a large number of important cohort series and retrospective series that are worth paying attention to. But these are the randomized ones. As any technology develops, it starts out as a preclinical proof of concept, and then it gets improved and developed. It's used in humans compassionately. It gets better. And then you get prospective cohort studies. And then usually you apply that technology and test it in the worst of the worst to begin, which is where we positioned the VANISH trial I'll talk about in a moment. And you can also position it as a proof of principle in patients who have other options. And that's where some trials have been done and some future ones are planned. So a quick historical review. SMASH VT was the first randomized trial of catheter ablation for VT. And it was published in New England because it really was a groundbreaking trial. It established that catheter ablation appears to be effective for treating ventricular tachycardia. If you had it to do over again, you would probably modify the design a little bit. But as a groundbreaking trial, establishing the effectiveness of catheter ablation, it's very important. And Vivek was kind enough to supply these following couple of slides to me, showing that it did not have an adverse impact, or in fact, any impact on mortality as measured in that trial, nor did it have an adverse effect on ejection fraction as shown by echo follow-up. So that trial took patients who'd had an episode of VT and were getting an ICD and ablated or didn't ablate and compared to no intervention. So good news, it was effective and better than doing nothing. The VTAC trial is the next important landmark trial in catheter ablation for VT. Important features of this is that it was a multi-center, multi-institutional trial published in Lancet. And they randomized, again, like SMASH-VT, a relatively small number of patients, 107 patients to ablation or no ablation after they came in with stable, hemodynamically tolerated VT. And they compared catheter ablation to not doing any intervention. And fortunately, catheter ablation is better than doing nothing. It reduces VT and VF recurrence significantly. But let's try to put those trials in a little bit of context. Small trials are inherently, why are we doing small trials? It's because they're hard to do. And second, they're expensive to do. And so it's worth getting everything out of it we can. So Etienne Delicataz did a sub-study of VTAC looking really an on-treatment analysis, similar to what Doug Packer just showed us about Kibana. Small trials are naturally fragile. They can be easily swayed by small changes in dropout or crossover. So when Etienne looked at an on-treatment analysis, it actually enhanced the measured effectiveness of catheter ablation for VT. Now this is a secondary analysis. The intention to treat analysis is the pure analysis of the intended treatment. But I think there's something to be gained in looking at the on-treatment analysis as well. So this is a paper written by the McMaster Group and my friend, P.J. Devereaux, on the risk of fragility in trials. Small trials are prone to error because of their small size. One or two patients going this way or that way can make a big difference. And that becomes important for the SMS trial. This was like the VTAC trial, but in patients who had non-tolerated VT. And that showed really no difference in outcome. The VANISH trial looked at sicker patients who had already failed antiarrhythmic drug therapy and compared escalating the drug therapy, which was a frequent clinical practice, to switching to catheter ablation for those patients. And we stratified it by whether they had failed Sotalol or amiodarone. And then they were treated either with more aggressive drug therapy, initiation of amiodarone or increasing the amiodarone, versus catheter ablation. And we found, fortunately again, that catheter ablation does seem to be effective. And it's more effective than being very aggressive with antiarrhythmic drugs. This is the combined analysis. But if the combined outcome of death, VT storm and shock, showed a significant reduction with ablation. But that was really driven by shock and storm, rather than by mortality, which did not show a significant difference. And there was an important effect, based on whether the patient had failed Sotalol or failed amiodarone. I'll quickly run through some of the sub-studies. The first is it matters which drug, the patients were on at baseline, but still no impact on survival. But an important impact on VT recurrence. So if patients failed amiodarone, no kidding, Captain Obvious, giving them more amiodarone is not going to do that well. So that was an important finding for us. Less of a trend in Sotalol. Cost effectiveness, very brief. Catheter ablation is cost effective. And in fact, if the patient failed amiodarone, it not only provides better outcomes, but is less expensive. So that's a rare finding in medicine. We looked at the maxillitine arm, and showed that maxillitine, if you're having to reach for maxillitine, you're having to reach. Catheter ablation's far better than maxillitine, which had very poor outcomes. Quality of life's very complex analysis. I don't have time to summarize, but in brief, catheter ablation led to improvement in multiple parameters of measured quality of life. There were some improvements in the anti-rhythmic drug therapy group as well, but less. We also found that induction testing does seem to be useful, and does seem to predict recurrences of VT. But for the sake of time, I'm gonna keep moving on. I just want to try to put all of those in context very briefly. So here are the main results from those four trials, and let's take a very quick look at what is coming up. So we've looked already at ablation compared to no specific treatment, and now we've looked at ablation for drug failures. I think the next natural question is what should be first-line therapy, and how soon should you intervene? So the upcoming trials are VANISH-2, Partita, PAWS, and Berlin. Berlin is going to be presented at late breaking this evening. It looks like it has terminated because of low enrollment on clinicaltrials.gov, but I don't know more information than that. I hope to be there this afternoon. PAWS SCD, Rod Tung's trial, is nearly complete enrollment. VANISH-2 I'll tell you about in a moment, and Partita as well. VANISH-2 is a trial of first-line therapy for ischemic cardiomyopathy with VT, and we are stratifying patients by their clinical characteristics to be in a Sotol-eligible arm or an amiodarone-eligible arm. If they're randomized to ablation, they get ablation. If they're randomized to drug, then depending on their known clinical characteristics, they will receive the drug that they are assigned. We've currently enrolled 210 out of a planned 366. Partita is a really interesting trial of early versus late ablation. The idea is that patients are implanted with their ICD and followed, and this is Paolo Della Bella's trial. They're planning to randomize 176 patients to either early ablation when they get a first shock or waiting until they get more VT. Bravely, they have powered it to look for mortality outcomes and hospitalization outcomes. PAWS-SCD will be the first trial that includes a significant volume of non-ischemic cardiomyopathy and will encourage epicardial Berlin, as I said, is being presented today. So we still have a lot of work to do. We need to know better ways to suppress VT, better ways to do our procedures, whether it's novel things like needles, radiotherapy, bipolar, electroporation, and so on. We need to know more about cost-effectiveness and quality of life. We need to know more about non-ischemic cardiomyopathy, and we do need to know what we're doing about mortality with all of these interventions. Thank you so much for your time. Thank you. Thank you, John, for the great overview. Are there, there are questions. Boris, please. Great presentation. Boris Schmidt from Frankfurt in Germany. One question, John. There, to the best of my knowledge, there's no randomized trial investigating the role of catheter ablation in patients with electrical storms. So really, the most, or the sickest patient. Do you think we can just extrapolate the subgroups that you investigate, you and others investigated, or do we need a trial in this situation? So Vantage II will allow VT storm patients to get in. It's very tricky doing trials of parachutes. So you can imagine what happens if you enroll a patient with VT storm, and they get randomized to drug therapy, and they keep having VT. So we've built in a two-week treatment period during which we don't count any events except death in Vantage II. But it's pretty easy to imagine that someone could still get ablated in that time period and cross over without reaching a primary outcome. Because as clinicians, we don't wanna wait till our patients are dead, just so that we can score one in the box of whatever they've been randomized to. So it's really very difficult to sort that out. Anyway, we can talk afterwards about exactly how we're trying to deal with that, but we are allowing those patients in the trial. I think it's particularly interesting because when we look at the trials that are there, usually those patients that are really doing not well, those with a very low ejection fraction or that are in poor condition do not benefit from catheter ablation as the others do with a better or preserved ejection fraction, right? Yes. I mean, similar to what we saw that Doug Packer present from Cabana, healthier patients do better. Yeah, thank you. We will move on. Thank you very much. And. Thank you.

Ventricular tachycardia ablation

Clinical trials

On-treatment analysis

First-line therapy

Research outcomes