You're listening to This Week in Cardiology from TheHeart.org, Medscape Cardiology. This podcast is intended for healthcare professionals only. Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD or Medscape. Hi, everyone. This is John Mandrola from TheHeart.org, Medscape Cardiology, and this is This Week in Cardiology for January 16, 2026. This week, some good listener feedback. one of the best studies of the year so far in AFib and heart failure, the exclusion of left atrial thrombus with different imaging techniques, and a report on an amazing, amazing cardiac procedure. So some listener feedback on my podcast last week, I talked about fish oil and risk of AFib. Professor Paul Dorian writes that EPA more than DHA may be the culprit. Dr. James O'Keefe, who has studied fish oil and written extensively about it, he writes to me that omega-3 produces a dose-dependent increase in vagal tone, which we all know that in susceptible individuals may increase AFib. O'Keefe adds that when fish oil is meta-analyzed, there is indeed a mace reduction benefit. Look at the recent PISCES trial, for instance, in dialysis patients, and he argues that fish oil may be most helpful in higher-risk patients. So his question is that in patients who could derive a benefit, the small increase in AFib risk may be worth it. Dr. James Stein agreed with my take that RCTs showing higher AFib risk should be considered over observational studies. And he sent me a link to a circulation commentary, first author Diane Fatkin, and I'll link to all these, which explores possible mechanisms of the relationship between AFib and fish oil, and the idea here is that fish oil may affect ion channels in a profibrillatory way. And some feedback on the vernicala and AF conversion. At least two European colleagues emailed me or mentioned that I did not mention flecainide as a converting agent for AFib, and this is true. Flecainide has been shown to be effective as an acute conversion agent, but it's not often used here in my zip code. But you know, if we accept butylide, amiodarone, certainly high-dose flecainide as AFib converting agents, it seems bizarre not to also accept vernicalent. Again, I'm not sure that the FDA in our ADCOM meeting that we had back in 2019 made the correct decision. The concern with vernicalent was side effects and adverse effects, but I'm not sure that if we looked hard enough, don't you think we could find terrible events that have occurred with butylide, imodorone, and high-dose phleconide? Okay, first topic today is the issue of withdrawal of heart failure therapy after AFib rhythm control. I'll report on a really superb RCT, a trial called WithdrawHF, and it was an Australian trial. But first, some background. One of the most common and actually nice things that I see in the EP clinic is when a patient who presents with heart failure and AFib gets better after rhythm control of the AFib. Now, this patient came in with AFib, very high ventricular rates, and definite pulmonary and systemic congestion. There was a high BNP. The echo showed an LVEF of 25%, and everybody agreed that there was congestive heart failure. So the smartest doctors that take care of these patients make sure to target the AFib as well. But too often, these patients with their soft blood pressures and rapid AFib, they're started on GDMT aggressively, and the AFib is either forgotten or it's deprioritized. And I think this is a huge mistake. And it's a failure, really, of EBM-101. And I say it fails EBM because GDMT in heart failure was established in mostly stable outpatients, most of whom actually had sinus rhythm. What's more, I want you to look up the Kotecha meta-analysis, Kotecha meta-analysis in Lancet, where Dr. Kotecha and he and his colleagues meta-analyzed the seminal beta-blocker trials for heart failure. and they separate out the effects of beta blocker in patients in sinus rhythm versus those in atrial fibrillation. And what they found when they looked at the comparison, the effect of beta blockers in patients in sinus rhythm versus AFib is that all of that benefit we love to cite from etoprolol-XL and corvedolol and basoprolol occurred in patients in sinus rhythm. The Kaplan-Meier curves for patients in atrial fibrillation was completely null. Now, again, before I tell you about the Australian Withdraw AF trial, please, my friends, when you have heart failure and acute new onset atrial fibrillation, please consider what my friend Dr. Rod Tong calls hashtag SRT or sinus rhythm therapy. Electrophysiologists want to help. We are here to help. Call us. Okay, the trial. Between 2021 and 2024 in multiple centers in Australia. First author, Dr. Louise Segan and colleagues enrolled 60 patients who had successful rhythm control of AFib and a normalized LVEF after sinus rhythm restoration. These patients were on greater than two GDMT drugs, and it was an RCT where one group had early withdrawal, that was group A, or delayed withdrawal of heart failure therapy, that was group B. Now, early withdrawal meant withdrawal right after the randomization and delayed meant after six months continuation. More than 90% of the patients had had catheter ablation as their AFib rhythm control strategy. Now, a period of six months off heart flare therapy was pre-specified as a safety measure given the findings from the TRED-HF. The TRED-HF, which I'll mention again, this was a trial that reported a relapse rate of 44% within six months, but that was among a diverse dilated cardiomyopathy patient population. So in withdraw, they had a 12-week protocol to wean the heart failure drugs. Interesting was that after six months, all participants then crossed over to the other group. This meant reintroduction of heart failure meds in the early withdrawal group. They did CMR, was done at baseline, and after each six-month period of the trial. You really should look at figure one in the European Heart Journal where they have a very nice trial flow diagram. It's an extremely clever trial. The crossover design was selected to A, ensure a similar follow-up between the groups, B, each subject could serve as their own control, which mitigates confounding, and it's good for secondary analyses, and three, crossover helps them to examine whether the timing of treatment withdrawal influenced the primary outcome. So a bit more on who were these patients. How did you get into withdrawal? Well, you had to have a prior diagnosis with an EF less than 40% during AFib. You had to have an absence of current heart failure symptoms. You had to be clinically ufomalemic. Current treatment had to be with two or more heart failure therapies because of course heart failure therapies had to be withdrawn That was the purpose of the study And before randomization the EF had to have normalized and be greater than equal to 50 on a CMR and there had to be no evidence of CMR myocardial fibrosis or delayed enhancement imaging, and NT-proBNP had to be normal. So normalized LVF was defined as improvement from an EF of less than 40% to greater than or equal to 50% at enrollment, and it had to be supported by normal pro-BNPs and no heart failure symptoms. And of course, sinus rhythm had to be maintained over the preceding six months. The NT pro-BNP threshold was applied to exclude individuals who have persistently elevated natriuretic peptide levels despite LVEF normalization and therefore they've identified a cohort with biochemical evidence of cardiac normalization and a lower likelihood of subclinical HF. And I will talk about in the discussion about these strict inclusion criteria. Now, a bit more on their weaned protocol. They were very careful. Beta blockers were weaned first to allow any early detection of AFib, then diuretics, then MRA, and lastly was the ACE ARBs. Then, after that 12 weeks, they did an echo, which was done to make sure there was not worsening of left-intrigative systolic function. Then patients went on for six months in that arm, then had the CMR. The primary endpoint was maintenance of a CMR normal EF of greater than 50% at six months. And of course, they had many secondary outcomes, some of which I'll mention. So let's talk about what they found, the results. They screened 139 patients to enroll 60. These were about 60-year-old, mildly overweight, mostly male patients, though there was an imbalance in the groups with 73% males in the delayed arm versus 90% males in the early arm. So the rhythm monitor was mostly with the cardia device, but a few had other cardiac devices that would measure for atrial fibrillation. And the key findings, during the initial six-month randomized phase, 27 of 30 participants in group A maintained a normal EF, that's 90%, compared with 100% in group B. The odds ratio for left ventricular maintenance in group A versus group B was 1.18, and the conference intervals were super wide. Then they did results of a multivariable regression, which this adjusted for any clinical and imaging covariates that they found that the left ventricular ejection fraction by CMR was not significantly different between the groups at the end of the randomized phase. and at six months, participants crossed over to the alternate treatment arm. Following medication withdrawal in group B, during the second six-month period, 28 of 30 participants maintained an ejection fraction greater than 50% following withdrawal of medicines. So in sum, a reduction in left-intrigal ejection fraction less than 50% was seen in five patients, three from group A during the initial randomized phase and two from group B during the crossover phase. The reduction in EF was not apparent on transthoracic echo, which was done four weeks after medication withdrawal. It took the CMR after six months. Left ventrigger ejection fraction reduction was accompanied by an increase in LV and diastolic volume and elevated pro B and P levels, but it occurred without clinical heart failure or any major adverse cardiac events. Arrhythmia recurrence occurred in one of these five individuals, but the mean AF burden was very low at 4%, and this led to the initiation of antiarrhythmic therapy. The characteristics of the individuals who relapsed were similar to those without relapse, and that's an important sentence. I'll come back to that. All five of these individuals experienced lev ventricular ejection fraction normalization following reinitiation of heart failure therapy. And as for AFib, it recurred in 26 of 60 participants overall. That's 43%. And again, there was a low AF burden on and off heart failure therapy, and there was no difference, 1.4 versus 0.6%. There were no major adverse cardiac events in any patient or any death in this study. The trial also had an optional extended follow-up period after the six-month crossovers were done, and 50 of the 60 patients remained off hardfire therapy after consulting with a treating cardiologist, and all 50 remained stable with normal left ventricular ejection fraction. So, the comments. The authors conclude three things, that in patients with normalized EF following AF rhythm control, the majority, 90%, exhibited maintenance of good EF at six months in phase one following withdrawal of heart failure therapy. Five patients, three from the early and two from the delayed group, exhibited a reduction in EF of less than 50% after medication withdrawal, but they did not have symptoms of heart failure or adverse clinical sequelae. The majority of participants who maintained LVEF and proceeded to the extended follow-up phase continued off heart failure therapy for an additional year and had stable ejection factions observed at 12 months. So I say to this, this is really important work, and it's an incredibly clever study design, and it appears to be a well-conducted study. It's truly remarkable clinical work from this team, and I wish we had more studies in cardiology like this. Now, we don't know what to do with these LVEF normalizers. Guidelines currently say to continue guideline-directed medical therapy indefinitely, But that is a lot of pills and a lot of burden for a long time. I mean, 50-year-olds who get better from their AFib after AF ablation have to take guideline-directed medical therapy with a normal EF for 40 years? It seems like a lot. And, of course, last year was a year we learned that it was safe to not use beta blockers when EF was normal after MI. That's a huge reversal. And of course, by not mandating beta blockers after MI, we have reduced the burden of being a patient in a lot of people. The question I think is this, is this work, is this data enough to make routine decisions with? Now, people will rightly worry because of the TRED-HF trial, which was heart failure, medication withdrawal in patients with dilated cardiomyopathy. This trial found a shockingly high relapse rate of 44%. The relapse rate in this study was only 8%, which makes sense because AF is surely a far more reversible cause of systolic dysfunction than dilated cardiomyopathy. Dilated cardiomyopathy is likely a disease of myocardial cells, and AFib can be reversed. Now, the five patients who had relapsed ejection infection are a bit worrisome, though, mainly because there were few, if any, predictors. except for one tiny little clue, and that is that those with lepintrigular ejection fraction relapses had enrollment EFs that was a bit lower, 52 versus 58 percent, among the non-relapse individuals. But as I've said before many times, it's really hard to parse an ejection fraction of 52 versus 58 percent. Now the other problem with these five relapsers is that it wasn really seen on transthoracic echo after just 12 weeks of medication withdrawal The authors do note that there was no sequelae and that all patients renormalized with basic RAS inhibition and beta blockers. Two of the five relapsers developed a left bundle branch block, so that could have been a clear sign to clinicians to relook at the LVEF. I think it's also important to remember when considering this trial for translation at the bedside is that withdraw AF included only patients with zero CMR-detected fibrosis and no other causes of left ventricular systolic dysfunction and no other indication to take therapy such as hypertension or diabetes. The authors are extremely honest about how their strict inclusion criteria limits the external validity of this because many patients with AF and heart failure have mixed cardiomyopathy. I would counter that by saying that a lot of patients with AF and left ventricle systolic function don't have mixed cardiomyopathy. A lot of them have AF as the main problem. Now, another lesson of this trial is that the good results underscore the importance of early recognition and treatment of the AF. Again, to my colleagues, phone an EP friend. We are here to help with your patients with AFib and heart failure. I love the author's extremely intelligent conclusion. It's exemplary, really. Read this trial. Quote, these results provide early insights into the potential feasibility of heart failure therapy withdrawal in AFib-related cardiomyopathy, but they should be viewed as hypothesis-generating. Larger, longer-term studies are needed to identify predictors of sustained recovery, optimal LVEF thresholds for withdrawal, and surveillance strategies to ensure safety. I might go further, though. I think this evidence provides at least a small reason to consider careful withdrawal in selected patients. These patients want to reduce pill burden. They're willing to have more active surveillance. A question I have for our listeners is this. To gather more confidence in these signals, do we need another huge RCT or could observational data provide enough of a confirmation? I actually think observational studies from these national registries might provide enough of a signal or perhaps even some embedded pragmatic trials. I'm pretty confident in these results because I have seen many patients do well with withdrawal of heart failure medicines after successful treatment of AF and LVF normalization. Now, I've seen this not because I'm specifically doing it all the time, but mainly because patients want to stop their medicines. And some of them did so whether or not I said it was okay. And these patients don't get recurrent heart failure, at least in my small experience. And I know my experience are anecdotes and anecdotes aren't evidence, but they're not nothing either. And I bet many of you seen this as well. I'm interested in your thoughts, and I congratulate the Australian authors on this wonderful study. Next topic is the matter of excluding left atrial thrombus before AF ablation. And I know this might be considered just an EP topic, but it's really not. It also involves my cardiac imaging colleagues. And I want to start off with some background and some bias. I'm plenty biased. I don't know about you, but I feel the same way about transesophageal echo as I do about cardioversion. I don't like either one of them. Cardioversion is my least favorite. It's rough and ugly. I get why it can be useful, but it's rough and I don't like it. And transesophageal echo is the same. It's hard on patients. Of course, don't beat me up. I know, I get that TEE is important, especially for valvular heart disease. But this notion that we have to do TEE before AF ablation is based on extremely poor data. I mean, we in Louisville don't routinely do TE before ablations, and we've had excellent outcomes with nearly zero stroke in thousands of cases. Not only don't I like TEs before ablation, I suspect that many of my imaging colleagues who have to interrupt their day to come to the EP lab don't like them either. And my final rant about TE is the matter of false positives. Remember, my friends, what we see on an ultrasound is actually just a shadow. There is no sign on that shadow saying it's clot or a prominent ridge. And all of this is why I'm drawn to an RCT published in JAMA Cardiology from Shanghai, China. This was a very simple trial. Patients going for AFib ablation in 10 hospitals were randomized to have left atrial appendix clot exclusion with T, and the other group got ICE or intracardiac echo. The primary endpoint was stroke, TIA, and systemic embolism, and I was so happy to read that because it's such a better endpoint than the surrogate measure of left atrial appendage clot. They had a non-inferiority design with ice being the new treatment and TE being the standard, and I'm also okay with that. Even though ice is probably more costly, it is being used often as a routine. In other words, we have ice in there, it's in the heart, and if the trial is positive, or non-inferior that is, then we can just substitute something that we're doing and we don't have to add the more invasive extra TEE. Now this was a very large trial. 1,800 patients in total were randomized. All patients in both groups had clear visualization of the left atrial appendage. Thrombus was detected in 18 ICE patients and 14 TEE patients. Interesting was that five of the 18 patients had thrombus detected outside of the appendage versus 0 of 14 in the TE group. Now, note to my left atrial appendage closure proponents who dismiss higher stroke rates in the left atrial appendage closure trials. Perhaps one of the reasons why a left atrial appendage closure percutaneously isn't so great at reducing stroke is because of the matter of clot outside the left atrial appendage. Okay, the main finding is that primary endpoint events, thromboembolic events, occurred in 4 of 906 patients in the ICE group and 5 of 904 patients in the TE group. That's 0.4 versus 0.6, which is essentially not different, and of course, it bet non-inferiority. Another interesting finding is that hospital anxiety and depression scores were significantly lower in the ICE group compared with the TE group, as well as periprocedural pain incidence was a lot lower with ICE versus TEE. Now, my comments. I also really like this study. Of course, RCTs are the way to answer this question. Notable here was the extremely low stroke rates, 0.4 to 0.6% respectively. And of course, when event rates are this low, you're going to have trouble making any comparison conclusions. But, but, similar to the recent anticoagulation discontinuation trials after AF ablation, that is, OSHIN and alone AF, you learn things when you have such low event rates. You learn that event rates are low. Now, no trial is perfect, but how great would it have been to have another arm where uninterrupted anticoagulation would have been a third arm? This would have given you a baseline with no imaging. Now I know practice patterns vary of course Europe USA I don know about China but ice use is nearly 100 in use in the U So if you worry about left atrial clot this study suggests it doesn prove, but it suggests that clot detection is as good or maybe better than TE with just the catheter that you already have in the heart. Now the monster caveat, I have to say, is that ice has a learning curve, and it requires some skill and manipulation and interpretation. You can't just put an ice catheter in the right atrium and spin it around and expect it to tell you clot or no clot. You actually have to move it and look, and you have to have some skills. So as for a matter of translation, I think this is similar to the Australian crossover withdrawal study that I just talked about. I think this data is strongly suggestive, but maybe not 100% actionable. I think this study just tells you that ice in skilled hands is non-inferior to TEE in 1,800 patients. And I like that because avoiding that big black tube that goes down a patient's throat is a nice thing to avoid. Obviously, this is one trial. I'd love to see more, especially with delayed phase CT imaging as a screening arm. My ideal trial would be ice versus TEE versus CT versus uninterrupted imaging alone. You need a huge number of centers and a huge number of patients, so I doubt this will happen, but it's nice to think about what this study would show, and I suspect there would be no difference. All right, the final topic today is this amazing procedure that's going all over social and regular health media, and it's a procedure that was done at Emory, and it's really one of the most amazing things I've ever seen or heard about. This was coronary bypass surgery without surgery. It was percutaneous aortocoronary bypass. Now, I want to say something before I tell you about the procedure. I'll keep these comments brief because this procedure may not evolve into anything. But this is a bit of a perspective on innovation, and since I'm old, I've lived through some of this. As I tell audiences of young people, the three procedures that I do as a routine, as an electrophysiologist in the community here in Louisville, Kentucky, I do conduction system pacing, cardiac resynchronization therapy, and AFib ablation, most common procedures, but they had not even been thought of when I trained. They weren't being done, but no one had even thought they could be done. What's more, I remember the day I was at a scrub sink when a pacer rep came up to me and said he was reading about a guy in California who was playing around was placing a lead in the coronary sinus to pre-excite the left ventricle and correct heart failure due to left bundle branch block. I turned to him and immediately said that would never work. Well, now CRT is a mainstay. Now, I wasn't around when Andreas Grunzig presented his first case of balloon angioplasty. That too must have been felt as an impossible thing until it wasn't. Like I say, things in cardiology are impossible until they aren't. So the journal CERC Intervention has published this amazing case report. It's open access and it's a great read and you should read it. It really is a good read. The problem to be solved in this case was what to do when you know a TAVI will shut off the left coronary orifice. Now you could do routine coronary bypass surgery, but this was a 67-year-old who had too many comorbidities, including end-stage renal disease on dialysis, previous BKA, prior stroke, bad ventricle. So this patient had had a taver valve degeneration and severe aortic stenosis, and the plan, valve and valve talvert, would have obstructed his left main coronary. But he also had severe calcifications that would have prevented other means of solving this problem, such as things like basilica, unicorn, cathedral, or snorkel stenting, which I have no idea about, but apparently are ways to get around this obstruction. Now, I surely can't properly describe this 8-hour, 26-minute procedure that had 3.8 hours of fluoroscopy time. That's why I think you should definitely read it and look into the details. But in short, the group used a combination of retrograde from RV through the septal perforators to the left main and antigrade, which was mean poking a hole in the aorta and attaching wires outside the left main in the pericardium to form a rail in which a Gore-Tex type conduit went from the aorta to the distal left main and then was attached with stents. The end result was that a patient could have the TAVR and indeed had obstruction of the left main and it wasn't a problem due to this bypass. Oh and then there was this blood in the pericardium from all this externalization was drained with a pericardial catheter. The authors report the patient is alive and well at six months. So in sum, this was a combination of electrosurgery and chronic total occlusion techniques, and it introduced several novel concepts, including the use of retrograde, aero-venous rail through the myocardium, intentional coronary artery exit using a stent and stingray strategy, an electrical surgical aortic exit to define the proximal anastomosis, And, of course, the authors add that the technique was accomplished in, quote, a hostile post-surgical pericardium with extensive adhesions. So my comments, I repeat, things are impossible until they are not. I'm stunned by what this team did. But I don't cover this because I think this could or should be duplicated. I cover it only to display the unbelievable skill and ingenuity of the operators and their team. and and because it so perfectly illustrates my belief that in the future the greatest challenge facing the modern cardiologist will not be having something to do for the patient but rather whether you should do it this man i'm sure is grateful for his extra six months but he also had end-stage valvular heart disease prior valve surgery he had kidney disease on hemodialysis he had severe severe peripheral artery disease with the previous right PKA and, quote, left leg critical ischemia, as well as an 11-trigger ejection fraction of 20%. In the real world, tomorrow, and this year, and maybe for years, this patient would be best treated by a palliative care doctor. Yet, we need teams like those from Emory to innovate. I don't criticize their decision to do this. We need the innovators. But we also need to promote common sense and compassion for people at end of life. And these are not opposing goals at all. So that's it for this week in cardiology. As always, I'm grateful that you listened and thank you. And remember, if you like this podcast, please take the time to give us a rating and write us a review. This helps others find us. And of course, if you disagree, send me a comment. I'm learning like crazy from these listener feedback comments. So thank you very much. Until next week, this is John Mandrola, From the heart.org, Medscape Cardiology. You're listening to This Week in Cardiology from the heart.org, Medscape Cardiology. This podcast is intended for healthcare professionals only. Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD or Medscape.
