Jun 12 2026 This Week in Cardiology

First, some listener feedback on my comments last week about the LOESE AF trial. A listener emailed me this week to let me know how much I missed in speaking last week about weight loss in atrophib. I covered the LUES AF study from two groups in the UK in a trial found that an intensive behavioral weight loss program induced weight loss but had no effect on any other AFib related outcome.

The listener and writer alerted me to three other studies that I should have mentioned, which were either not mentioned in the Louis AF manuscript or mentioned only superficially. It turns out that there are strong signals of benefit from behavioral guided risk factor management in atrial fibrillation, including weight loss. Let me briefly review these because I think it's worth doing so. Uh the arrest AF trial published in Gemocardiology in 2025, 122 patients with obesity and AFib.

Undergoing initial AFib ablation, they were randomized to a lifestyle risk factor management program versus standard of care in Adelaide. This is the Adelaide program. The active arm lost nine kilograms more weight and and had a forty seven percent reduction in the primary endpoint of freedom from AFib at twelve months after ablation.

Secondary measures were also improved, including AFib symptom severity and a 10 millimeter decrease in blood pressure. Second, European Heart Journal published the Dutch POPAF trial. This randomized 145 patients referred for PVI, and this was to a nurse-led integrated lifestyle treatment program before ablation or standard care. The intervention arm in uh Netherlands uh patients lost six kilograms more and had a fifty one percent reduction in the primary endpoint of repeat ablation.

or cardioversion in the first year. As in the Australian trial, blood pressure was also reduced in the active arm. And thirdly, Jack published the Prague 25 trial in 2025. This was 200 patients with an interesting comparison. These patients had obesity and AFib, and they were randomized to lifestyle modification, diet and exercise, plus anti-arrhythmic drugs. versus catheter ablation alone for P uh PVI.

The intervention arm lost six point seven kilograms more, but catheter ablation did better at reduction of the primary endpoint of being free of AFib, seventy three percent in the ablation arm. versus 35% in the lifestyle plus antirhythmic drug arm. And non-inferiority was not met, and it was superior for ablation.

I actually covered this trial last summer and my take was that even though it sits in Jack as a negative trial for lifestyle fa uh risk factor management, the AFib burden and quality of life scores were similar in Prague. And the lifestyle management group lost more weight, had better hemoglobin A1C, and even a better VO2 max on the treadmill. So I considered it a very positive trial. Now, all of these positive trials have serious limitations in that they are small,

mostly single center and obviously unblinded. They are at risk, therefore, for the normal performance bias seen in pragmatic trials. That said, though, regardless of AFib outcomes, the lifestyle interventions resulted in superior metabolic health, and that may be as important as AFib outcomes. Imagine a future where these interventions are combined with GLP1s. And honestly, this might slow the AFib epidemic.

All right, I also had feedback on my comments on the Flecca ED trial. Dr. John Ralshus from South Carolina writes that my enthusiasm for IV fleccionide superiority over IV amularone in patients. with stable CAD without ischemia is quote at odds with the reality that you yourself highlighted in that many Hemodynamically stable patients with PAF self-convert with beta blockers in time, and providing them with an anticoagulant may be all that is needed. End quote.

Uh J.R. worries that if I V fleccionide were let loose in the real world where many EDs have no cardiology support, safety may be an issue, and I always agree with safety concerns. Now I went back and looked at my comments and yes, maybe I was a bit too muddy on the matter. I was indeed positive about the trial. IV fleckenhide was clearly better than amniodorone, which is a lousy cardioversion trial.

But then I noted that the race seven Dutch trial showing clear benefits of delaying cardioversion versus early cardioversion. I guess I would clarify these statements by saying that the vast majority of patients with new early AFib can be managed with time, reassurance, and follow up. But when we think cardioversion may be useful, uh say let's um a more symptomatic patient Who really wants to come out of AFib, IV fleckonide is a lot better than Amyodorome.

Finally, on feedback, my comments on the negative Leave HF trial, and this was of the ILR Implantable Loop Recorder Guided Management of Heart Failure. This from doctor Mark Lewis Baker. I offer his comments with a direct quote, it's so good that I really have nothing more intelligent to add. He nails the human nature part of caring for people in medicine.

Quote, the problem with heart failure is really a social one. When there is a disconnect between the alert and the intervention as mentioned in this recent trial, it is because there aren't enough people to care for heart failure. and the failure of cardiomems, for instance, and complaints from the FDA about company nurses displays this problem. The company nurses offered good interventions, not thought of by the burned out staff in the trial.

He continues, doctors want to fix things. It's why we do ablations and stents and heart failure doesn't offer that immediate gratification. A device monitor can help alleviate the strain of the chronic care team and very bluntly can help with funding for a problem that nobody wants to pay for. It's not a sexy problem identified with celebrities and youth. Humans want to help other humans, but they also want to see their intervention have effect in a short attention sp span period.

That doesn't happen with heart failure therapy. Someone has a heart attack, you open the artery, and you feel good about what you did. As silly as this sounds until heart failure and other chronic medical issues are made to satisfy the mental health of their caregivers. This problem will persist. If we continue to ignore the mental health of our caregivers who treat these chronic conditions, these problems persist.

Thank you, Dr. Mark Lewis Baker. All right, first topic for today is transcatheter tricuspid valve replacement. The TriSend II trialists have published a paper on the cost of adverse events after transcatheter tricuspid valve replacement with the Edwards Evoch valve.

They analyzed a hundred and fifty five patients who had had the valve as part of the TriCENT2 study. The main reason I highlight this cost of adverse events study is that the frequency and severity of the adverse events shocked me, truly. I think it's worth going back to the original TriCen two trial and think about this intervention.

As always, the three tenets of tricuspid regurgitation hold true. A TR is common and contributes to serious morbidity in patients with heart failure. B TR is almost always secondary to the adaptive or maladaptive processes of R V and L V, adaptation in heart failure and C, surgical intervention to for isolated TR is a highly morbid procedure.

Procutaneous strategies therefore hold great promise, but since there are so many patients with TR and doctors make money from doing these procedures, the risk of indication creep and overuse is real. As you all know, I look at this problem as a neutral Martian. I don't do these procedures, though I often get involved after the patient has hard block and then needs a pacemaker.

New England Journal of Medicine published the original TriCEN2 trial in october twenty twenty four. About four hundred patients with symptomatic TR randomized in a two to one ratio to the tricuspid valve replacement with Evoc or medical therapy alone. Uh hierarchical composite endpoint of death, RV assist device, post index, tricuspid valve intervention, hospitalization for heart failure, improvement in KCCQ, improvement in New York Heart Association, functional class.

And 30 seconds gain on a six minute walk test favored the valve replacement group. Of course it did. The win ratio analysis, however, was driven by valve interventions, KCCQ, and New York Heart Association improvement, all Subjective endpoints vulnerable to the bias of an open label trial done at centers that love doing interventions, an open label where one group gets a big procedure and the other group gets white tablets.

More objective endpoints, such as death, heart failure, hospitalizations, and six-minute walk test, were not different. As for safety, get this. Severe bleeding occurred in 15.4% of patients in the valve replacement group and in 5.3% of those in the control group, highly significant P value. And permanent pacing uh occurred in 17.8% of patients in the valve arm versus 2.3% in the control arm.

in the follow up studies, where only a hundred and fifty five patients of the two hundred and fifty nine total had available cost data, the authors report that complication occurred in twenty percent of patients, most commonly new pacemaker or severe bleeding. Pause. Pause there. One in five patients had severe adverse events. Now not surprising at these add substantial cost to the procedure.

The paper did not uh uh tally any extra cost in the control arm, likely because there were so few compared with the valve replacement arm. Now the new paper, Instructural Heart, doesn't really add much to our knowledge. Rather, it brought my attention to how bad this procedure is. I mean, what are we doing?

The seminal trial, trisent two, finds no difference in objective endpoints such as death. There wasn't even a reduction in heart failure hospitalizations, which that too is remarkable because this endpoint is highly susceptible to bias. Now, if you have this valve versus medical therapy, you are nine times more likely to need a pacemaker. And m not an easy pacemaker, by the way, because we don't put leads through

the valve replacement and that that means a leadless pacemaker or a a C S lead and you have a three times more likely to suffer severe bleeding. And for that you get no reduction in death or heart failure hospitalization. In my opinion, this whole thing is a failure of both regulation and critical appraisal.

Looking back at this trial, Trisun two might be worse than Triluminate, which is the tricuspid transcatheter edge to edge repair trial, and I did not think it was possible to get worse than triluminate.

Next topic is on disease creation, the CKM syndrome. Now journalist Crystal Fend has nice coverage of its first ever guideline for CK CKM syndrome. It reads sort of like a comic tragedy repeated since the creation of prediabetes and pre hypertension. But remember, whenever you have a new guideline, you always have something underneath. And here we have three branded drug classes SGLT2 inhibitors.

GLP one agonist and the always positive non steroidal mineralicoticoid antagonist pheneradone. So if we have these three branded drugs to sell, we must have to create a disease. Enter CKM or Cardiovascular Kidney Metabolic Syndrome. I kid you not. No longer, my friends, should CV health be separated from metabolic and kidney health. It's all one disease now. CKM comes in four stages. You'll you'll love this. Stage one, a person is just obese.

Stage two, obese with high blood pressure, triglycerides or diabetes. Stage three, CKM is quote with subclinical CV disease and CKM risk factors such as a high prevent score. uh or very high kidney disease risk by uh by being and get this and i don't quote this i'm gonna read this slowly because i can't believe it Kidney stages G three A with A three, G three B with A two A three, or G four G five range. I swear that I I I read that as written. That's not me having a TIA.

And then of course stage four includes having disease, atheroscleric cardiovascular disease, or heart failure, or stroke, or PAD, or even AFib with obesity. Now figure four in a circulation guideline paper is a quote CPR framework. Calculate, personalize, reclassify, CPR framework for primary prevention of cardiovascular disease. This figure has seven rows, ten columns, and twenty decision arrows at least.

And my criticism of this is similar to the lipid guidelines. It's too complex and too self evident. Come on. I mean, you have three stages of this new syndrome, and not one of them has any disease. They just have abnormal lab value. I mean you can be obese, minimally mobile, a smoker, and if all your labs are okay, you barely have CKM. I ask, do we really need a many thousand-word document and new disease name to counsel patients on weight loss?

And treat them with SGLT2 inhibitors when they have type 2 diabetes or CKD, and to treat them with GLP1s when they have obesity, diabetes, sleep apnea, or ASCVD. And don't get me started on phenerinone, because every positive trial of this drug is marred by the fact that it is compared against placebo instead of spiritolactote. Another problem with these diseases is it scares patients.

I can't tell you how many times patients look at me and they tell me with great sadness, like they have cancer, that they have stage three kidney disease, which sounds terrible. Then I look at their creatinine and it's 1.5. So I think we we should just get along with fewer diseases and fewer treatment guidelines, and this is a classic example.

All right, I want to go over now two trials that are peripherally involved with cardiology that teach super important EBM lessons, one in New England, one in JAMA. I and maybe you don't treat patients with sepsis, but we've all seen the Surviving Sepsis Campaign, SSC, and these are guidelines which give what some call a weak recommendation for early high-dose IV fluid.

According to ICU doctor Josh Farkas, these have these guidelines have been weaponized as quality measures, performance measures, and it's resulted in doctors being pressured to prescribe arbitrary volumes to patients. And I I have seen patients diagnosed with sepsis then flooded with fluid who then developed worsening respiratory failure due to ARDS or or even just pulmonovascular congestion.

Another approach to early sepsis treatment is the more restrictive fluid resuscitation and earlier use of vasopressors, and previous trials of these two strategies have been inconclusive. So New England Journal has published the large Arise Fluids pragmatic trial of the two strategies. The primary outcome was a good one. This is a good good one. Days alive and out of the hospital from randomization to ninety days.

Approximately 1,000 patients were randomized. And the first thing is that they tell you is that patients in the vasopressor group received less fluids, about a liter less on average. And the percentage of patients who received vasopressors was 19% higher in the vasopressor arm. And this speaks to fidelity with the trial procedure. The primary endpoint was about as null as null can get. At day ninety, the median number of days alive and out of the hospital was seventy six in both groups.

Other secondary measures were also not different, and one safety outcome was different. Only 0.6% of patients in the vasopressor arm had pulmonary edema versus five percent in the fluids group, and that's a relative risk of 0.12 or an eighty-eight percent reduction in the risk of pulmonary edema. So my comments and and here I'm just gonna quote Dr. Josh Farkas and I'll send you the the link to the tweet that he put up. He said quote

This is a great example of the overreach of guidelines and protocolized medicine. People get all upset about practice variation, so sometimes they try to stomp it out using guidelines and protocols, but these guidelines are highly fallible. So what may occur is that you standardize care in a way that harms everyone equally. That's so good, isn't it? It's also about the more thinking about where these guidelines came from.

Farkas noted that they were initially motivated by raging cases of toxic so shock syndrome, and he used the example of Rory Staunton, who's a twelve twelve who was a twelve year old from Queens. who grazed his arm playing basketball, was sent home with band-aids and later died of overwhelming sepsis. I mentioned this trial, end story, because it is yet another example of how well-intentioned guidance can run amok. This Arise Fluids is a great trial, but it should have been done a long time ago.

You would hope that one of the role of our professional societies would be in preventing such medical reversals. I I I think instead of cozying up with industry or promoting rent seeking money extraction programs like the ABIM testing initiative, A better role for our professional organizations should be that they're beacons of science wherein academics prevent overreaching guidance. They'd promote proper trials before coercing doctors with ill-guided performance measures.

Note that the trial does not say to use high dose fluids or earlier vasopressor. It merely says that one is not superior to the other and there should be no protocol for all patients with sepsis. Thus, the use of high dose fluids is no more a quality measure than the length of, say, the review of systems in the notes.

All right, next trial. Bicarbonate, sodium bicarbonate for inpatient cardiac arrest. This is the BI. Bicarbonate hospital cardiac arrest trial? I guess that's what B I H C A stands for. Now, despite the lack of evidence, many doctors give sodium bicarb as an acidic buffer to patients who have cardiac arrest.

This is one of those old school plausibility arguments and uh uh the summary of it would be that cardiac arrest causes low perfusion, which creates an acidosis, which then hampers cell function. And correction of the acidosis with bicarb creates a more favorable healing milieu. It turns out the current guidelines do not, do not recommend bicarb, but no matter, doctors do it. I've seen this done honestly since the 1990s, and it's still done to this day.

Now we turn to Denmark, where nearly 3,000 patients in 21 hospitals were screened, 913 determined eligible, of whom 779 were randomized. to IV bicarb or placebo in the setting of in hospital cardiac arrest. The primary endpoint of return of spontaneous circulation occurred in thirty-nine percent in the bicarb group, thirty-seven percent in the placebo arm, and you don't need statistics.

But if you'd like, that's a risk ratio of 1.05 with lower bowel 95% confidence role 0.88 to 1.24, p-value 0.62. Note the tight conference intervals wherein the lower bound was zero point eight eight or twelve or twelve percent, which pretty much excludes a clinically meaningful benefits. At 30 days, 12% a sodium bicarb group versus 9% in the placebo group were alive. Risk ratio 1.25. Now, favorable neurologic outcome was also not different. Nor

Were there any signals in the subgroups? So for those doctors who think they can identify a specific sort of patient who will benefit from bicarb, there were surely no obvious signs of treatment effect heterogeneity in the in the paper. Comments here. Another classic example of a strong trial where a high percentage of eligible patients were included. It was placebo-controlled and had good primary outcome choice.

I really like the c outcome choice of reper return of spontaneous circulation. It's better endpoint for one dose of bicarb than say favorable neurologic outcome because obtaining a favorable neurologic outcome is down the road and and between the IV infusion and down the road, there are many confounding factors on that causal pathway.

If effective, bicarb is supposed to aid in the immediate recovery. That makes return of spontaneous circulation a better outcome. And it's good thinking about the choice of primary endpoints. This reversal in medical practice is even stronger than the sepsis reversal because there was actually zero prior evidence that bicarb was effective. So now you have a terribly pessimistic prior distribution.

and combined with very strong null data uh showing no benefit. So if you combine those two curves for a posterior distribution would yield absolutely no reason to use this intervention in cardiac arrest. In fact, I I think after this data, the use of bicarb for in hospital cardiac arrest may be a marker for a dumb clinician who does not use evidence.

Okay, final topic today is about the decline of ventricular tachycardia in patients with heart failure. Europace has published a super nice observational study from the EP group in Basel, who consistently put out great work, both in the form of observational studies and trials. The paper is titled Contemporary Trends and Outcomes in European ICD Recipients, a 15-year analysis. The research idea is to understand temporal trends and how the ICD is functioning.

It's important, right? Because the seminal trials of ICD benefit in patients with heart failure were done more than 25 years ago, and heart failure therapy has improved quite a bit. This was in two centers, Erasmus in the Netherlands and Basel University Hospital in Switzerland. The group analyzed just under 2,200 patients with the ICD implant. About 60% had had the ICD for primary prevention.

The total time period that they looked at this was from 2002 to 2017, broken into four time periods. That was oh two to oh five. oh six to oh nine, ten to thirteen and two thousand fourteen to two thousand seventeen. And the primary outcome was first appropriate ICD therapy. It could be ATP, anti tachycardia pacing, or shock for ventricular tachycardia or ventricular fibrillation censored at 16 months.

Now the baseline characteristics yielded some expected findings. Recipients had modestly higher left ventricular ejection fraction and better functional status with higher GDMT uptake over the years. The key finding was that at sixteen months, appropriate ICD therapy declined from thirty five point seven percent in the oldest time period, oh two to oh five, to twenty point two percent. in tho 2014 to 2017, driven by fewer VT events. They went from twenty nine point eight to twelve point seven.

Whereas VF remained low and did not change materially. Overall mortality did not differ significantly across the time bars, but the proportion of deaths classified as arrhythmic deaths decreased. In adjusted analysis, the QRS duration independently predicted ICD therapy, whereas left ventricular ejection fraction was not independently associated with the CD. Later implantation eras had lower odds of therapy.

So my comments is the first thing to say about this is an excellent use of observational data. It doesn't try to compare two therapies, it just tells an important story that the amount of ventricular arrhythmia in heart failure is plummeting. It confirms an important observation from the heart failure trialist who published in the New England Journal of Medicine in 2017. This is also a seminal paper, first author Shen et al. and I'll link to it.

That when that group looked at forty thousand patients enrolled in heart failure trials from nineteen ninety-five through twenty fourteen, the rate of sudden cardiac death has declined substantially. Specifically, in the observational study of RCTs at heart failure, the cumulative incidence of sudden death at ninety days after randomization was two point four percent in the earliest trial versus one point zero in the most recent trial.

Now the cause of these declines in VT is likely multifactorial, but obviously, surely, better GDMT is a likely reason. Both the Basel analysis and the New England Journal of Medicine analysis end in two thousand seventeen, but I really wonder if we had a another time period, a fifth time period from two thousand seventeen to two twenty six, I strongly suspect V T would be even lower because medical therapy is even better. Oh, that's just a prediction and me thinking.

The main teaching point of these of this data is that the declining rates of VT and sudden death set the stage for new trials, retesting the primary prevention ICD. In an era when heart failure therapy was weak, the proportion of sudden death to heart failure death or all cause death was high enough that the ICD lowering sudden death was enough to move all cause death. But now, if VT is occurring less, you'd expect the ICD benefit to be lower.

And since the ICD comes with a fixed finite risk, that harm benefit calculus no longer favors the device. This is exactly what happened in the Danish trial where non-aschemic cardiomyopathy, there was no ICD benefit. A data like this should strengthen the equipoise needed to enroll in the European Profid trial of ICD plus guideline directed medical management versus guideline directed management alone in ischemic chromosity patients.

We should have the bravery to randomize in trials and reanalyze uh MADA to in the modern era. So that's it for this week in cardiology. As always, I'm grateful that you listened. Thank you. And remember, please take the time. Uh, to give us a rating, write us a review. The listener feedback this past week was excellent. Send me that if you don't agree with anything. Until next week. From home in Louisville, Kentucky, this is John Mandrola from the Heart.org Medscape Cardiology.