Jun 13 2025 This Week in Cardiology

0:00 [Music] You're listening to this week in cardiology from the heart.org Medscape Cardiology. This podcast is intended for health care 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 Mandola from the heart.org Medscape Cardiology and this is this week in cardiology for June 13th, 2025. Today I'm recording on a warm sunny day in London where I'm here to speak at the London Arhythmia Summit. I'll talk today about listener feedback and cardiac sarcidosis, sinus node ablation, surgical AF ablation, reducing outcomes in patients with chronic kidney disease and type 2 diabetes and recruiting for cardiac

0:48 trials. The first topic is listener feedback on cardiac sarcidosis. Now, one of the best parts of this podcast is the listener feedback I receive this week. David Bernie, the division chief of cardiology at the University of Ottawa and an academic electrophysiologist who's active in sarcoid research, sent me feedback on a paper from Dutch and American authors that I had covered two weeks ago on May 30th, 2025. The mostly Dutch-led paper had 1500 patients with biopsy proven established sarcidosis, most of which were non-cardiac. The question they had was how to risk stratify for an ICD. Now the two ways of risk stratification were to either use professional society recommendations or

1:34 to use CMR. CMR was grouped into four categories. One high-risisk category and the three were lower risk categories. The high-risisk category was quote pathology frequent LG. The three main findings were that if either the professional society criteria or CMR indicated a high risk, the V the rate of VT at 5 years was also high. Up to one in three patients had VT. The second finding was that CMR had the better C statistic compared with the risk criteria from professional societies. The C statistic was quite good at 0.86. The third and most sobering finding was that ICDS treat sudden death and being wrong is fatal. And yet the prediction

2:20 missed some patients. And this is what Dr. Bernie was writing about. That is the nuance of risk stratifying for an ICD in patients with suspected or documented cardiac sarcidosis. Now one of the most common ways that patients with cardiac sarcoid present is with AV block at surprisingly young ages. When a 75year-old presents with AV block, it's surely due to aging. But when a 50-year-old presents with AV block, we should be thinking about cardiac sarcidosis. And Bernie writes in an email, specifically in CS patients who present with advanced conduction system disease and metabolically active disease, they seem to be at a very significant subsequent risk of VT andVF even if they have a normal EF. He cited

3:07 a s a study from cirp 2018 which showed that AV block even with a normal EF had a 5-year VT rate of nearly 10%. Now, it's not clear why this is and research is ongoing and Bernie says it may partially actually be related to steroids citing a paper and one of his papers in JCE and the title of that paper was treatment with steroids was associated with an increase in ventricular arhythmia burden in patients with clinically manifest cardiac sarcoid. Now he has that most of us in this field regard this subgroup as an exception to any sort of LG cutoff or pattern rule quote unquote. Indeed due to increased awareness of cardiac sarcoid and CMR and

3:54 PET now we are increasingly diagnosing these patients earlier and there are reports where the PET scan is positive and the MRI is actually negative. that is the disease is picked up so early in the process that scar has not yet formed. These findings led Dr. Bernie to strongly recommend that all patients in the subgroup are recommended to have an ICD regardless of LG. He and colleagues are currently updating the HRS guidelines on all of this, hoping to be published early in 2026. He also wanted me to plug a cardiac sarcoid conference that he's hosting August 24th to 25th in Ottawa. Thanks to Dr. Bernie for updating me and the this week in cardiology listeners.

4:39 All right, second topic is inappropriate sinus tacic cardia. I'll start by saying pulse field ablation is white hot and so it had to happen. Heart rhythm cage reports which is a really great journal has published a case report of a group who failed to resist the urge to mess with a sinus node. Yes, it happened. A group of ablation doctors report the first case of using PFA to ablate the sinus node in a patient with purported inappropriate sinus tacoc cardia or IST. I don't usually cover case reports, but I want to mention this report because of the seriousness and danger involved. First, some background on IST. ISTD has been around since I was in training. I

5:26 know this because we tried ablating situs nodes in the 1990s and it went terribly. It either did not work or injured the frenic nerve or it caused symptomatic junctional rhythm and some patients had to have pacemakers. I tried it a handful of times earlier in my practice and it still did not work. Many of my colleagues thinks ablation of the sinus node doesn't work because of the difficult anatomy of the sinus node which is a not in one place b often epicardial and c in close proximity to the frenic nerve and anatomy may indeed be problematic but I think the far more important reason that ablation is a bad idea for IST is that the cause of IST is unknown and likely not cardiac and this

6:11 is the key problem. If the sinus node is normal but receiving disordered neural input, then ablating the normal structure is not going to work. It's sort of the AF ablation problem on steroids. Yes, there are a few variants of atrial fibrillation that are clearly a form thrust of an atrial tacocardia like a focal AT from the PVs as was described by the Bordeau 25 years ago. But most AIB occurs because of a mixture of triggers and substrate and metabolic factors. We ablate the PVs and sometimes it works. Well, ablating the situs node for IST is even worse because IST is surely caused by something extracardiac. I mean, perhaps it's an autoimmune condition more often seen in women and surprisingly women who work in the

6:57 health field. Anyways, the the case report involving using PFA to ablate the sinus node. This patient, they report, had a pacemaker already because of an overzealous previous sinus node ablation attempt. The pacer was no longer pacing because the IST had recurred, which is often the case. The authors tell us that PFA worked, heart rate was reduced, and the 34 year old woman felt better with atrial pacing and had persistent junctional rhythm at 90 days. 90 days. If I had reviewed this case, I would have strongly urged the editors not to publish it. One reason is that the woman had morbid obesity. So I questioned the diagnosis of inappropriate sinus tack. Morbid obesity can surely cause sinus tack due to a combination of deconditioning and genetic factors. In

7:45 other words, the sinus tack may not have been inappropriate. The second issue is that we only get 90 days of follow-up. Who knows whether the heart rate will come back and who knows what will happen with her pacemaker in 5, 10, 15, and 20 years. We also get no discussion in this report of the long-term risks of a 34year-old with a pacemaker. This, my friends, should be avoided in the most strenuous ways. When she is my age, 30 years from now, she will have 30year-old leads. Then what happens when she gets infection out of a generator change or there is lead failure? I want to also mention some of those who are advocating a combined surgical hybrid thoroscopic approach wherein a surgeon does epicardial linear ablation to isolate the sinus node. I will cite a

8:32 non-random comparison study from 2022 where the surgical linear ablation approach compared favorably to the endocardial ablation approach. But of course we know that approach does not work. This study included authors who were employees of Atriure, the company that makes the linear ablation device. It was not randomized, not blinded, included no sham procedures. The control arm of endocardio ablation we know does not work. So there was a very very weak study. My take of this whole space and condition is that research should be focused on the causes of IST. I warn my car colleagues not to run a muck with PFA. I understand the urge to do something aggressive for these patients because IST does cause a lot of symptoms. Care of these patients requires tons of

9:19 empathy, honesty about uncertainty, patience, and reassurance that this condition will likely improve with time. IST is similar in some ways to potent things like supine exercise often works, but not right away. PFA makes it easier to destroy cardiac tissue, and that's good in the left atrium because we can avoid a fistula. But IST should infuse us with great caution. To be honest, I am not even sure there is enough equipoise to even propose an RCT including ablation as an arm. I am not sure if I would recommend randomization if I had a patient with IST to a trial that included extensive ablation of the sinus node. All right. Third topic is survival after surgical AF ablation during cabbage. Now

10:08 the first thing to say about surgical AF ablation especially concominant ablation at the time of surgery holds great promise. The patient is already there being operated on the extra risks are minimized. Plus these patients often have significant structural heart disease. The problem in this surgical AF space is there's limited data. There's multiple approaches and there's varied patient patient patient presentations. We simply don't have cabana-like data for surgical AF ablation. Probably the best comp compilation of data is a metaanalysis from the group of Richard Whitlock, first author Graham Mccclure in the European heart journal in 2017 9 years ago. Now they metaanalyzed 23

10:54 RCTs and found that surgical AF ablation did reduce AF compared to no ablation, but it did not reduce stroke or mortality. The key finding there was that only one of the 23 trials was considered low risk of bias. All the trials included but one had moderate to high risk of bias. So we desperately need more data on surgical AF ablation. Not only because it's potentially very helpful procedure, but also because it can be incomplete or what I call willy-nilly ablation to add an extra CPT code. This is especially bad because it can lead to left atrial flutters or poor atrial transport function. So a recent retrospective observational comparison study published by a number of academic

11:40 surgeons in the annals of thoracic surgery has stirred some conversation online. It stirred conversation because the group who received surgical ablation had a significant survival advantage. The data source came from Medicare patients who had had ablation at time of cabbage which also includes hospital and surgeon volume as well as the surgeon's preference for doing ablation. Some surgeons do it a lot and others do it very little and that is a hint actually. The primary endpoint was all cause mortality, which I often like as an endpoint because it is free of ascertainment bias, right? You're either alive or dead. But it is not a great AF ablation endpoint because exactly zero non-h hard failure trials of AF ablation

12:25 show mortality reduction. And that's because reducing AF burden is unlikely to reduce death because of so many competing causes of death. And that too is a hint. Now, this study had a twist though in the comparison which is necessary because literally everyone knows that healthier patients are more likely to get concominant ablation. The authors did something else to try and sort out that obvious confounding. They did an instrument variable analysis wherein the authors used surgeon preference for ablation as the instrumental or IV variable. Here's how it works. Some surgeons frequently perform ablation. greater than 40% of their cases. Some surgeons rarely perform ablation less than 5% of their

13:12 cases. A patient's treatment depends partly on which surgeon they happen to see and this creates at least from a patient perspective a quas randomization. Then the authors do the two parallel analysis. Both require propensity matching techniques of course. The one analysis is the as treated which is a direct comparison of patients who get ablation versus those who didn't. This is the traditional and highly biased approach. And then they did a surgeon preference analysis where a patient with AF is sort of randomized and which surgeon operates on them. And if surgical AF ablation reduces mortality, surgeons who do it more often should have lower mortality. This approach is somewhat clever and interesting because if both analyses show similar results,

13:58 it somewhat strengthens confidence that the findings are real rather than simply due to selection bias. And that's exactly what they found. In the as treated analysis, surgical ablation had a 4.4 month survival advantage. In the surgeon preference analysis, this was a nearly fivemon survival advantage. And the concordance led the authors to strongly conclude our findings support current guideline recommendations for surgical ablation during cabbage in patients with AF and it highlights that ablation is currently underused in contemporary practice. My comments. I am very warm to the possibility that concominant surgical amphablation may be

14:45 a good thing to do for some patients with coronary disease and cabbage and AF. But this study does not support anything. Nor does it suggest AF ablation is underused. Despite doing this IV analysis, which sounds great, this is still a non-randomized comparison. There is likely selection bias that cannot be overcome by matching. For instance, surgeons who do more AF ablation may see different types of patients. They may work at a better hospital and do better followup. And these are the things that randomization usually takes care of. But that's not the main reason I don't put any weight on this study. The main reason is that the authors found no difference in the incidence of stroke in the two groups with either of the

15:31 asreated or surgeon preference analysis. So I ask if the ablation of AF is so good good enough to reduce death how does it not reduce stroke and if it doesn't reduce stroke how does it reduce death what's the causal mechanism I don't see a mechanism for reducing death especially given all of these other competing risks that patients with cabbage have what's more this finding contradicts the Whitlock meta analysis of 23 RCTs ease which showed no reduction in death with surgical ablation. So based on that metaanalysis of prior trials, your belief has to be extremely pessimistic. And if it's extremely pessimistic, it would take strong evidence to change about a

16:17 thousand times stronger data than this. What's more, the mortality curves in this paper separate by only 4 months after 5 years. This seems to me like a very minimal difference. and separation over that long a time seems more related to either healthier patients getting surgical ablations or perhaps better health care, better health systems or it may just be noise. Now I want to continue my friendships with the cardiac surgeons. They do important work. We need cardiac surgeons. But I would also suggest as humbly as possible that they need to improve when it comes to evidence generation. To me there seems to be a huge need for proper RCTs of standardized surgical AF ablation techniques. Endpoint should not be all

17:03 cause death. It should be AF burden and stroke incidents. Given the increasing prevalence of AIB and coronary disease, I would think this would be a fantastic place for the new NIH leadership to invest money in. All right, next topic is finerone with emboglyosin and CKD and diabetes. The confidence trial. Now I realize that this week in cardiology is a cardiology podcast, but we have yet another big randomized control trial of finerone, the newest mineral receptor antagonist or MRA. As an EP doctor in the southeastern United States, that's our unhealthiest geography. I see many many patients for AIB who also have type 2 diabetes and

17:49 CKD. It goes with the territory. If you are an AF patient, obese enough to have type 2 diabetes, you likely have some CKD. Now, I scratch my head these days because type 2 diabetes patients. There are so many drug classes available. Which one should we use or should we use both? As if all of these drugs were generic $4 per month tablets. They're not. New England Journal of Medicine published a confidence trial Wednesday and there was a great discussion about it online. I discussed it today because it provokes me to think about science questions versus marketing efforts. Here's the deal. Patients with type two of diabetes who were taking an ACE or ARB and had CKD as defined by an increased urinary albamin to creatinine

18:35 ratio. And I know cardiologists don't use this number. I don't. Just think about it as enough CKD to spill protein which is bad and it seems to correlate with CV outcomes. The study treatment arms were finer alone, AMPA alone or the combination of the two. Primary outcome was change in the urinary albiman to creatine ratio. About 800 patients were randomized in the three arms. The main result was expressed in relative risk reduction and at day 180 day 180 the urine albimman creatinine ratio results were finerone had a 32% reduction ampa alone 29% reduction and the combination therapy had a 52% 52% reduction from

19:22 baseline and so the reduction with the culmination therapy was 29% greater than that with either drug alone. Both were highly statistically significant. Adverse events in drug dis discontinuation were similar though there was a decrease in eGFR greater than 30% at day 30 in two times more patients in the combination group though the GFR improved at study end when the drugs were stopped. In addition the frequency of hypercalemia was relatively lower by approximately 15 to 20% with combination therapy. So my comments for the optimistic or maximizer docs as I call them the previous model was sequential initiation

20:07 of these two drug classes. This trial the confidence trial shows that simultaneous initiation seemed to work better. But there are many critical is appraisal issues here. So many in fact that I think it makes me wonder whether this was just a marketing exercise to sell more finer known. The most obvious issue is the end point no end point surrogate endpoints we can say that your cholesterol level your blood pressure your creatinine these are surrogate markers and most patients don't care what their LDL is or their blood pressure is that doesn't affect how they feel well the urine albamin to creatine ratio is even more esoteric and likely even less of a surrogate marker than say

20:52 LDL or blood pressure the point of kidney protection strategies is to lower kidney outcomes, less dialysis, less a doubling of the creatinine, less cardiovascular events. I realize that the urine to albamin creatin ratio is easier and it may be an earlier sign, but let me just quote the author's own words to underscore the uncertainty of this endpoint. Here's a sentence I quote. We speculate that taken together these data suggest that the reductions observed with combination therapy with EMPA and phenarinone will probably correlate with meaningful reductions in the risk of progression of chronic kidney disease. I mean this is truly remarkable in the New England Journal of

21:38 Medicine. We speculate probably correlate. Wow. Then there is a matter of only a six-month trial. These were 67y old patients. How long are we supposed to use these two classes of meds? Forever? Really? Then there is the matter of a 44day screening period before randomization. They screen 1600 patients and excluded half. Why? They don't say. At least I couldn't see it. Highly selected patients though is not nefarious. Lots of trials pick the perfect patient. But I mentioned the screen to randomize information because it speaks to the generalizability of the data. Finally. And I sound like a broken record on this podcast. Whenever finerone is used in a trial, there

22:23 should be an arm for spirolactone or eperinone. That way, we would have an idea of the incremental value, if any, of the new non-steroidal finer known. In the end, I think confidence trial was a marketing exercise. It does not change practice and six-month data of a very surrogate endpoint hardly meets any regulatory standard. The next topic today is about recruiting for important trials and the status of EP as a profession. Journalist Sarah Freeman reports from the meeting of the British Cardiovascular Society in Manchester, which I was lucky enough to be asked to speak at last year on a session describing difficulty in recruiting patients for two important clinical trials. I wanted to cover this because it's

23:10 important. I can add a third trial that is also noting slow enrollment. Now in the UK, the craft HF trial compares surgical versus catheter ablation in patients with heart failure. This is a hugely important question, right? For multiple reasons. The first is that despite my friendship with Nasir Marouch, Christian SS and Philippe Summer, the PIs of Castle and Castle HTX, the numbers of heart failure patients in trials of AF ablation are few. The event rates are low and the evidence for AF ablation in heart failure I think is limited. Craft AHF would be a great ad to this evidence base. What's more, patients with heart failure often have atrial structural disease making them less

23:56 likely to be a PVI responder and surgical AF ablation could also remove the left atrial appendage epicardially. That maneuver has been proven effective in Laos 3. I think surgical AF ablation could beat catheter-based ablation. The main problem with recruitment is the strict entry criteria of the craft HF trial and indeed this is the problem in heart failure at AF as the chief weakness of the castle trials were the highly selective entry criteria. Now the second UK trial having problems recruiting is the British trial of using SCAR on CMR to determine ICD implantation in patients with non-eskeemic cardiammyopathy. Now British has a really brave protocol. Get this. Patients have a non-eskeemic

24:43 cardopathy EF less than 35 and have a scar on CMR. These will be randomized to either an ICD or CRTD versus an ILR or CRTP. basically no backup ICD. This is exactly the kind of information we want to know. It's such a beautiful study question. The third trial I want to mention and I traveled to Berlin a couple months ago to speak about it is the bravest of them all. The proof trial which seeks to replicate mate 2 years ago. Made it 2 is a schemic cardiammyopathy with EF less than 30 and the ICD reduced mortality with an N&T of around 20. The idea behind proof is that sudden death rates and heart failure have fallen, medical therapy has improved, and the delta

25:31 between the ICD arm and medical arm is surely less. Well, proof 2 has had slow enrollment for a couple reasons. One is that there aren't many terrible eskeemic cardiammyopathy patients out there anymore thanks to the interventional cardiology community and rapid PCI during STEMI. The second issue is that at least in Germany, if you are a doc who randomizes a patient to profit and they are randomized to the medical arm, you lose reimbursement for the ICD. I highlight this topic mostly for my EP colleagues. While PFA holds all the excitement in our field, we have stalled in terms of new major evidence development. PFA is nice especially for patients but if we are to maintain our

26:16 stature as a profession we need to support those who seek to answer important questions like craft HF like British and proof. So that's it for this week in cardiology. As always I'm grateful that you listened. Thank you. And remember, if you like this podcast, please take the time, give us a rating, write us a review, and by all means, if you have something to add and I didn't get something quite right, please send me a note or write a comment on the website. I learn a lot from these and listener feedback has become a great section. Until next week, this is John Mandola from theart.org Medscape Cardiology. You're listening to this week in cardiology from theart.org. or Medscape

27:03 Cardiology. This podcast is intended for health care professionals only. Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD or Medscape.