Feb 20 2026 This Week in Cardiology

0:00 You're listening to this week in cardiology from the heart.org Medscape Cardiology. This podcast is intended for health care professionals only. [music] 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 February 20th, 2026. This week, longerterm data in Evolute low-risk tavi trial, a provocative metaanalysis, DNR, targeted hypothermia, good news in hepath evidence, GLP1 agents as AIB drugs, and the evaluation of patients with chest pain. There was big news in the Tavy versus Sver in low-risk patients. This week, Jack

0:47 published six-year outcomes of the Evolute low-risk trial, and there were surprises. Now recall that the evolute low risk was first published in the New England Journal of Medicine in 2019. This had 1468 patients with severe AS and they were randomized to the self-expanding Medronic TAVI valve versus surgical AVR. This study had a non-inferiority design with a primary endpoint of death or disabling stroke at 2 years and it was analyzed with basian methods. The trial found a greater than 99% probability that tavi was non-inferior to surgical AVR or saver. Now many trials have shown similar outcomes for tavi versus saver

1:33 at 2 years. Low surgical risk patients though want to know about longer duration outcomes including the valve reliability and the intervention or reintervention rate. Now before I say anything about the results, I have to say that both the balloon expandable and self-expanding trialists have been excellent about reporting longerterm outcomes. I mean other than the partner 3's mysterious change of primary endpoint, the entire evidence landscape of TAVI versus surgical AVR has been pretty exemplary. All right, the main results of this six-year trial, the primary composite endpoint continue to be death or disabling stroke. However, changed is that the trialists no longer analyze by basian methods and they no longer use

2:20 non-inferiority. Now the analysis is superiority using KPIMER estimates. The composite of all cause mortality or disabling stroke was 23.3% for TAVER versus 20.4% for surgery. That difference was 2.8 eight percentage points higher for TAVI. This fairly large absolute risk increase did not come close, however, to reaching statistical significance. The p value calculates at 0.43. At this six-year report, many of the patients had seven-year outcomes and at seven years with a vital status sweep, the mortality rates were more divergent. 27.7% for Tavy, 23.9% for Saver.

3:09 Cardiovascular mortality was essentially identical between the groups 11.1 versus 11.0%. A major point of emphasis and a new finding came when they looked at reintervention rates which were similar at 5 years but divergent in years 6 or seven. namely cumulative reintervention rates were 5.5% versus 3.3% at 6 years. That p value was 0.07 and it rose to 9.8% reintervention tavy 6.0 reintervention surgery at 7 years. Now that p value is 0.02 in favor of surgery. Now I know that you could easily gloss over the medical jargon reintervention but I would not. Why? Because

3:56 reintervention for TAVER can be quite serious, especially if it is surgical as it was in twothirds of the reoperations in this trial. Because observational data have shown death rates as high as 13% when you have to operate or cut out a tavy valve and replace it with a surgical valve. Now, the reintervention death rates were only 3.3% in this trial, but these were low-risk patients and these were highly skilled operators. In other words, I guess I'm just saying that reintervention in tavi is a really serious outcome. Now, the causes of reintervention are important. The rates of intervention for aortic stenosis of the boprothetic valve was similar in the two groups, but more patients in the tavy arm had reintervention for aortic insufficiency than those in the savver

4:43 arm. And that could be important because as tends to be slow and AI might be more acute. Now, seemingly perplexed by the higher reintervention rates, the authors did an exploratory analysis, looking at the use of something called postdeployment balloon dilitation using a balloon larger than the valve waste. This they termed offguidance post-dilitation. And this exploratory analysis showed a just barely significantly higher rate of reintervention in patients who had offguidance dilitation. And so the proponents could say, "Aha, just don't do offguidance dilitation and all will be good." But I I guess I would caution against this sort of thinking because a the association could be noise wasn't

5:30 that significant and b doctors aren't doing dilitation willy-nilly, right? They do it because they see a potential problem like non ideal valve expansion or maybe a paravalvar leak. And so there could be reverse causality or confounding. It might not be the offguidance post- dilitation. It might be the reason that they were doing offguidance post- dilitation. Now, there's also a suggestion that older evolute valve types may be causal in these reinvention rates and newer iterations may be better, but of course, we don't have six-year datas on these newer valves. So, my comments on this whole thing from a neutral perspective, the first thing to say is that we've got to take the view of a patient, right?

6:16 Even if a tavy is one or two or 3% worse at 10 years, I think rational people, some rational people might favor the substantially less invasive procedure. I mean, it takes months to recover from open heart surgery. So, there is that. But many 65 or 70 year old patients with AS would care what happens when they get close to 80 years old. a substantial difference in mortality would would would be something that many people would consider really important in their decision. Now the other thing to say or to start with is that tavers may be similar to PFA in that not all TAVs are the same right the higher reinervation rates seen with Evolute in this trial have not been seen with balloon expandable valves but but not only is

7:05 the reintervention worrisome the death signal also looks worrisome to me I mean it's 3% higher death rate now I don't really think you should ignore a a nearly 3% higher rate of death than the tav taver arm. Now, Dr. David Conn pointed out online to me that a p value of 0.4 suggests it is not surprising given a null hypothesis of no difference. But I would counter that by saying that a typical analysis of Kepla mer curves requires something called proportional hazards over time. And this is not the case in these trials. As the Kappa Meyer curves cross, there's early tavi benefit and it changes to a later hazard. And this means that there are non-proportional hazards. Now, I know

7:51 this sounds like gibberish, right? But it is not kind of gibberish. And how do I know that? Because the same journal, Jack, has published a review article discussing the problems and analytical solutions for non-proportional hazards. And I'll link to that. The second issue I have with the higher death rates in the tavern arm is that the original Evolute trial used a non-inferiority design with a non-inferiority margin of 6%. Which seems kind of high to me, but nonetheless 6%. Starting with the three-year analysis, and I'll link to all these papers, the authors changed to a superiority testing strategy. I could not find anywhere where that was prespecified. Now at seven years the authors write in a discussion section that quote there are no significant differences were

8:38 observed between the treatment arms for all cause mortality but listen to the numbers 27.7% taver 23.9% surgery now the difference in higher death rate is 3.7%. The 95% confidence interval goes from minus 2.4% to 9.9%. The p value is still not anywhere close to significant, but the upper bound is 9.9% worse. That's well larger than the 6.6% non-inferiority margin. Not only that, but something is changing over time in these mortality curves. If you combine reports of death from the 4-year evolute paper to this paper, here's what you get. The tavern mortality goes from

9:25 9% to 27.7%. That's an increase of 18.7%. The saver mortality goes from 12.1 to 23.9%. And so saver mortality is only increased by 11.8%. I wonder had the authors stayed with their basian design, what would the probability of Taver having a higher death rate at six or seven years? I don't know. I suspect it would be pretty pretty high. Now, you think I'm being too harsh on Taver? Well, what about the recently published BMJ Hart meta analysis first author Marinqartas at all? This was updated 5-year outcomes of TAVER versus SAVER in low to

10:10 intermediate risk patients. And I'll link to that. It's open access in heart. They metaanalyzed six trials in about 7,400 patients and they found that the relative risk for all cause mortality was 1.12 and the credible intervals went from 1.02 to 1.22 with no heterogeneity. That's a 99.3% posterior probability that saver was superior to taver for the endpoint of mortality at 5 years. For stroke, the median relative risk was 1.13. The credible interval went from 0.93 to 1.39 with very little heterogeneity and that resulted in an 88.0 posterior probability that saver outperformed

10:56 TAVER for stroke outcomes. Now, proponents of TAVER may argue that a 2025 meta analysis, first author Rohan Ready, and I'll link to that in Jack found five-year results better for TAVER. Yet, that metaanalysis weighted trials with shorter results, specifically the dedicated evolute four-year trials. Now, one final thought. The UK TAVI trial was a pragmatic randomized trial comparing TAVER to SAVER in low-risk patients in the UK. The one-year results were favorable for TAVER and it was published in JAMAMA and I'll link to that. The five-year results were presented during Euro PCR in May of 25. The results were far less favorable for TAVER. This

11:44 report found the statistically significant and clinically relevant increase in in stroke in TAVER patients 12.9 versus 7.3% that P value was 0.01. And again, in the UK TAVI 5-year results, there was a numerically increased mortality in TAVER patients. It's now February of 2026, 11 months later, and the data has not been published. In some, my comments on TAVER remain the same. It's an amazing procedure for high-risisk patients with AS. It's probably a very good procedure for intermediate risk patients, but for low-risk patients, I have concerns over valve reliability, reintervention, and higher stroke rates. Now, the investigators get credit because they're presenting this data, but I have to say

12:30 the curve crossing is worrisome. A young patient with aortic stenosis needs to know this information because it's relevant to their shared decisionmaking. All right, next topic briefly. What about DNR in the hospital? Well, I came across a really interesting viewpoint paper in JAMAMA on documentation of get this unilateral DNR orders which I did not know existed. Now, normal practice or a standard DNR is requested and agreed on by the patient or the patient's surrogate. Yet, there are many cases when clinicians know that CPR is not only feudal but also totally inappropriate clinically. In this case, I learned from this editorial from doctors Pisatello, D.

13:15 Martino, and Parker that a unilateral DNR can be placed. A unilateral DNR is a DNR order that does not require a patient or a surrogate consent. This is indeed an area of medical ethics controversy. The most obvious reason for such an order is that CPR, which is a medical intervention, is felt to be contraindicated in the same way that an ablation or heart caization or PCI would be contraindicated. I also learned that clinicians often document unilateral DNR decisions by placing a standard DNR order in in the electronic health record, rendering them indistinguishable from a DNR order entered when a patient or surrogate requests to not receive CPR. The three authors argue that this is

14:01 unethical because it obscures the unilateral aspect of the decision. They have a nice figure in their paper about the types of DNR, specifically the unidirectional DNR, where there is conflict from the patient's surrogate who wants CPR and when the patient's surrogate ascends to no CPR more covertly. When there is conflict, the authors argue this is clearly a unidirectional DNR. However, the authors note the more common uh type of unidirectional DNR is a just a covert DNR. Let me quote from their writing. Quote, "An ascent unidirectional DNR decision occurs when a clinician makes a unidirectional DNR decision and the patient or surrogate disagrees with the decision but either does not express

14:48 disagreement, does not demand CPR, or has a preference to receive CPR, but chooses to defer to clinical decision-making." So, one of the main thrusts of this short editorial is that currently there is poor documentation of unilateral DNR orders and these could contribute to inconsistencies in patient care. For instance, the authors write that the lack of awareness that a DNR order was a unilateral clinical decision decreases the likelihood that clinicians will re-evaluate that order for patients whose clinical condition improves. I actually had a similar situation occur to me when a patient with VT storm decided that uh she did not want any more CPR. Things were really bad and it was a good decision. But then the VT

15:34 stopped and uh two months later a doctor called me and said, "Sean, this patient shouldn't be uh DNR." And we agreed and we changed. The authors call for hospital systems to create and implement a unidirectional DNR order that's unique from a standard DNR. This type of order, this unidirectional DNR should include specifications within the order that require clinicians to regularly re-evaluate the code status that the patient clinically improves and is to designate whether patient or surrogate disagreement exists with the order. Now, one consequence they write of such a visible policy would be to increase visibility of these unidirectional DNR decisions and potentially normalize use of unidirectional DNR decisions and influence clinicians to more regularly

16:21 invoke this mechanism. Now, I highlight this important piece and topic because one of the greatest stresses I have in the hospital is contributing to bad deaths. Interventional cardiologists like EPS and others are often put into this situation because events like MIS, heart block or VT are often signals of a dying patient. We see someone who has no chance of meaningful survival from our interventions and further resuscitation is not only not beneficial but directly harmful. And we hope that a family discussion goes well and that we are allowed to provide comfort and dying process. But at times there is no family or the family is unsure and there's a need for some sort of unilateral DNR

17:07 orders. I don't think I've ever come across a direct conflict with a patient, but surely we all have had some degree of ascent or covert unilateral DNR. But you know, I don't really see the ethical tension in this. Do you? if you do see tension. One example I took from a nice discussion the authors had on the Jerry Pal blog and I'll link to that was that when we do CPR, when we're actually doing the 20 to 30 minute and procedure and it isn't working, there comes a time when a clinician decides to stop. That's a pure clinical decision. And I don't really see that as any different from not beginning CPR in the first place. There are days when I feel my greatest contribution to patient care that day is

17:53 helping a patient and a family get a DNR order so as to avoid harmful end of life care in that person. All right, next topic is yet another failure of targeted hypothermia in the ICU. I'm sorry and I'm going to keep this brief because I am triggered by the fact that for years my ACLS module keep kept forcing me to go against a mountain of evidence against targeted hypothermia in survivors of out of hospital cardiac arrest. We are better now at not doing this but cooling patients who survive cardiac arrest persisted well after multiple trials found no benefit. I've written about it. I've podcasted about it. I've tweeted about it and no one seemed to care. it does not get any

18:39 attention. So, cooling continued. And when I asked about it in the ICU, it was like asking about not giving the patient clean air and water. Well, Jamma Neurology has 2-year follow-up from an RCT called the TTM2 trial. Recall that the original publication of TTM2 was in the New England Journal of Medicine in 2021, and I'll link to that. This was 1850 patients who were randomized to a target of 33 degrees hypothermia or targeted normal thermia with early treatment of fever and they found no differences at mortality at 6 months a hazard ratio of 1.04 and no differences in poor functional outcomes at 6 months. The Gemma Neurology paper looked at two-year outcomes in the 84%

19:25 of patients who had follow-up. And again, there were no differences in any four measures of neurologic outcome, which strongly suggests there was no long-term benefits either. I just wonder how much money we wasted and how many patients were harmed by aggressive cooling over the decade or so that it was done. Okay, let's do good news. Good news and hep evidence. Hardfire cardiologist and nice guy Ryan Tedford posted on X News of trial of a trial design and rationale paper for a device called the Aperture trans catheter shunt system. Of course, I had no idea what this is, but I read about it and it's amazing. Apparently, the

20:10 device is a left atrial to CS shunt. And the paragraph describing the procedure in the rationale paper really made me smile smile because I thought my gosh these interventionalists are crazy. Get this. You go into the right in J. You go into the CS distal CS inflate a balloon then a wire and a needle that puts a wire into the left atrium from the CS. So you're puncturing. Then you balloon the hole between the CS and the left atrium. Then you place this shunt catheter which then stays there to shunt LA volume to the CS and the RA. This is shocking in its bioengineering. I have no idea if it will work. I seriously doubt it will work. But if you were a

20:58 proponent and you wanted to show that it works, you would do it in the sort of triluminate way that you would do a trial comparing people who had this shunt to a group that got white tablets and then you would measure quality of life. But thankfully, and the reason why I highlight this paper is that's not what the alt flow 2 trialists are going to do. Not at all. This trial will include a sham control arm with blinding of patients and doctors. And this is why I highlight this rationale and design paper. The only way to assess subjective endpoints from procedures like this, including even our procedure AF ablation, is to do it with proper sham controls. So I say congratulations to

21:45 the trialist, the first author Dean Keryakas from nearby Christ Hospital in Cincinnati, Ohio. Okay, next topic. GLP1 as AF drugs. The journal Europace has an observational study worth thinking about. It's from the big EP group in Milan, Italy. They did a single center propensity matched study of obese patients BMI greater than 30 who had first time catheter ablation for PAF between 2019 and 2024. One group initiated semiglutide within 3 months before or one month after ablation versus matched controls who did not receive any GLP-1 therapy. All patients had loop recorders which is good. The primary outcome was AF beyond

22:31 the two-month blanking period. The final cohort included 181 semiglutide treated patients versus 181 controls and they were matched clinical and procedural characteristics. At 18 months followup freedom from recurrence of aphib was 80% in the semigluton arm versus 65.2% and that was a hazard ratio of 0.52 a highly statistically significant and of course weight and BMI decreased significantly in the semiglutide group and a substantial portion of GLP-1 treated patients achieved greater than 10% weight loss. So my comments methodologically this is about as weak as it gets right it's single center it's

23:18 non-randomized it's non-b blinded I mean the loop recorders are a positive because it detects all aphib but otherwise this is very low-level evidence but I highlight it because we know that weight loss is strongly associated if not causal in improving AF outcomes in patients who have obesity. We know that weight loss improves left atrial structure and electrical properties. We know that weight loss improves blood pressure and glycemic control which also have positive effects on the LA function and structure. So the findings are totally mechanistically plausible. This week I met the Novo Nordisk representatives in town who made rounds in our office because oral semaglutide is now available. I have yet to

24:03 prescribe these drugs. We were hesitant like this with the SGLT2 drugs because they were felt to be the realm of diabetes doctors. But then it became clear that SGLT drugs were cardiac and renal drugs. And I think we're at the same place with the GLP1 drugs. It's time. And I am optimistic that GLP-1 drugs may become one of the best AIB drugs ever developed. It's surely going to be better than doneterone or sodtool or amiottoone. That's it for this week in cardiology. As always, I'm grateful that you listened. Thank you. And remember, if you like the podcast, take the time to give us a rating, write us a review, and by all means, if you don't agree with something I said, send me a note. We'll do some listener feedback. Until next week, this is John Mandola

24:51 from theart.org, Medscape Cardiology. [music] >> You're listening to This Week in Cardiology from Theart.org, Medscape Cardiology. This podcast is intended for health care professionals only. Any views expressed are the presenter's own and [music] do not necessarily reflect the views of WebMD or Medscape.