Mar 27 2026 This Week in Cardiology

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Start using Medscape AI on the web or in the Medscape app. Medscape AI, trusted medical intelligence. Hi everyone, this is John Mandrola from the Heart.org Medscape Cardiology, and this is This Week in Cardiology for March 27th, 2026. This week, early aortic valve replacement and aortic stenosis, left atrial appendage occlusion in jamma cardiology, and a big ACC preview.

First up, let's talk about early aortic valve replacement. New England Journal of Medicine published long-term follow-up of the South Korean recovery trial of early aortic valve replacement versus conservative care. In patients with severe aortic stenosis, Now the first publication of recovery was in twenty twenty and it had six years of follow up. This one has twelve years of follow up. Now right there you're squinting, right? Because most patients with aortic scenosis are near

80 years old. But that's one of the many interesting things about this trial. The mean age of patients was approximately 64 years. The primary endpoint was operative mortality and CV death. 145 patients were randomized. Just one hundred and forty-five. A primary endpoint event occurred in two of seventy-three patients. That's three percent in the early surgery group.

and in seventeen of seventy two, twenty four percent in the Conservative care group for a hazard ratio of get this zero point one zero, ninety five p percent conference intervals to zero point zero two, to zero point four three and p value very significant. Death from any cause occurred in eleven patients in the early surgery group and in twenty three patients thirty two percent in the conservative care group, that hazard ratio of zero point four two and also highly significant.

This is very similar to the report in twenty twenty where it was one versus eleven primary endpoints for a hazard ratio of zero point zero nine. The interesting thing about this long-term follow-up is that 85% of the conservative arm crossed over and got AVR. Only 11 of 72 or 15% of patients in the conservative arm did not get surgery, which is shocking when I th tell you the entry criteria.

Patients had to have very, very severe stenosis, aortic valve area less than 0.75, a peak velocity greater than 4.5 But the enrolled population were even worse. The mean aortic valve area was zero point six three and the mean peak velocity was five point one meters per second. I think this is plays into why there's a ninety percent reduction in the primary endpoint. These were relatively young people with few comorbidities.

hence only two primary outcome events and twelve years in the early A VR group. The severity of this asymptomatic aortic sinosis in quotes is also in question because Ten patients died before getting their valve replaced, and 20% of those who crossed over, one in five, had urgent aortic valve replacement. That's kind of strange to go from asymptomatic to urgent AVR. Another curious thing about this trial is the tiny number of events, two versus seventeen.

I calculated a fragility index and it was only three three events would have changed it to non significant, despite a hazard ratio of zero point one zero. Now look, I don't disbelieve the results. What I do question is were these patients really asymptomatic? This trial assessed symptoms by history alone, and everyone knows that aortic stenosis is slowly progressing. And it gives time for people to adjust their activity.

So in the end, what I take from this paper is that if you have someone like these patients, a literal pinhole, I'd be darn sure they don't have symptoms. And if they truly did not have symptoms, say they passed the treadmill, then I would follow them very closely. Based on the small number of patients, two thirds of whom had bicuspid valves.

and the extreme severity of the AS in these cases, along with their low comorbidity, I would not use this study as a reason to do early aortic valve interventions in a more common aortic stenosis patient who is elderly, more complex, and has lesser degrees of aortic stenosis. And I certainly wouldn't use this data to translate it to doing early Taver in patients in their mid-60s, that young of an age.

All right, next topic is major bleeding with an amulet and watchman trial in jamma cardiology. The first author of this paper is doctor Boris Schmidt's. This was a secondary analysis of the amulet IDE trial conducted from twenty sixteen to twenty nineteen. Now rather than reporting on the primary device comparison between AMULET and Watchman 2.5, the authors report on major bleeding events.

The original amulet IDE trial was a head-to-head comparison of the two different left atrial appended closures devices. The five-year results of the original AMULET versus Watchman 2.5 device were published in Jack in 2024. Stroke and systemic embolism were similar at seven point four versus seven point one percent, as was major bleeding at twenty point one versus twenty point zero. Basically the same.

This paper, the one in jammocardiology, combined all 1800 patients in both arms to assess predictors and outcomes of major bleeding. Now the authors felt justified in doing this because the hazard ratio on the device arms was one point zero, so it was no different. Briefly, these were seventy six year old patients with a mean chad's bass score of four point eight.

There were six findings. The first was that major bleeding occurred in roughly one in five patients, approximately eighteen percent, which seems like a lot. Annualized that was six percent per year. Second finding, the timing pattern of major bleeding was very distinct. In the first six months after the procedure, the annualized major bleeding rate was 20.5% per year.

After six months through year three, it was three point nine percent per year. I want to insert a note here that patients cannot exclude their periprocedural time. Though proponents like to talk about less bleeding in the later part of a study, the patients are part of both parts.

Third finding, most of the bleeds were GI, fifty-seven percent. Fourth, predictors of the bleeds were will not surprise you. All of the typical features, right? Older age, female sex, diabetes, previous bleeding, kidney disease. Notably, the device type, the anti thrombotic regimen at discharge, and device related imaging findings did not predict bleeding. This suggests to the authors that bleeding risk lit lives in the patient more so than in the procedure.

Fifth and perhaps most notable finding of this entire study is that nearly half forty seven percent of the major bleeds occurred in patients on no antithrombotic therapy. Sixth finding in a comparison piece between patients who had a major bleed versus those who did not. Patients who had major bleeding had significantly higher rates of everything bad.

uh strokes, systemic embolism, cardiovascular death, 32.5% versus 18%. And this was driven by higher strokes. So patients with major bleeding have more than double the number of strokes. Uh same thing with cardiovascular death. All cause mortality was also higher in patients with major bleeding. And major bleeding was fatal. Bark score of five in 25 patients or 1.4%.

And the authors concluded that major bleeding was common in this high risk population, largely related to the underlying patient factors. Early major bleeding was highest in the six months after appendage occlusion, then it dropped considerably. Most events were GI bleeding and occurred even in patients on minimal or no antithrombotic therapy. Major bleeding after appendage closure was strongly associated with all bad outcomes, including stroke and mortality.

I find this an interesting paper. First, you have a relatively low annualized stroke rate of about 1.5 to 3% per year, but nearly a 6% annualized rate of major bleeding. patients who had major bleeding clearly did worse in all aspects, including thrombotic events like s uh stroke, N C V death, and all cause death. What this tells me is that we should definitely have a trial In older sicker patients who have a high bleeding risk of left atrial appendage closure versus no anti thrombotic.

Now, every time I discuss this at meetings, people worry about you wouldn't do anything for the patient? No therapy? I hear this all the time. But this study I'm discussing from some of the best centers in the world, finds a super, super high rate of major bleeding in the first six months, annualized at twenty percent per year. So therefore, the patient randomized to the nothing arm

starts far ahead in the probability game of stroke and bleeding. In such a trial of appendage closure versus no antithrombotic, the left atrial appendage occlusion arm has to overcome a very high major bleeding risk in the first six months. And since no study that I know of finds that appendage closure reduces ischemic stroke, and surely not taking any anti-thrombotic will have less bleeding, I propose such a study would be halted early for harm.

Well the other thing this paper tells us is to look at the subgroup analysis of Champion. Champion's coming up in in ACC. I've written about it and I'll talk more about it later in this podcast. In the closure AF trial there was no heterogeneity based on Chad's less than or greater than four. But Champion has three thousand patients, which is larger than closure. They may be able to sort out some heterogeneous treatment effects.

The amulet IDE study is highly relevant to the current practice of appendage closure because at least in the US, left atrial appendage occlusion is used in patients with high Chadzvas score. Much higher than was in protect and prevail. Now, if you believe that left atrial appendage occlusion works at all, and I don't believe it, but if you do These older patients may be A more susceptible to major bleeding, as shown in this paper,

and B more likely to have a competing or non left atrial appendage cause of stroke. A champion's three thousand patients may allow us to make some conclusions on the performance of the device based on the severity of the underlying disease of the patient.

Okay, let's do an ACC preview. Well, I leave for New Orleans in just about an hour here in the morning. There will be some practice influencing trials presented. More than I would have expected. Here's a brief previous preview. The chip BCIS3 will test the common use of the micro-Axial flow pump AKA Impella as an LV unloading device during high-risk PCI.

Chip BCIS3 is an incredibly important question because impellate use in high risk PCI is a place where the extra reimbursement could induce overuse. I mean high risk PCI is in the eye of the beholder and the doctor can just say it's high risk PCI, put in an impella and make a bunch of extra money. Chip BCIS three is funded by the UK government, which makes sense because the UK government is the payer, and it is important to show the device improves outcomes.

Now you don't see the Impellum Makers funding trials on this question as the device is already approved and it's accepted and it's used. In fact, this is a common theme of AC stud ACC studies. Uh look at the funder of a study and consider the two purposes of clinical trials. First purpose is to answer an important scientific question. The second purpose of trials is to sell more product, science or marketing. Just just consider that when you're looking at trials.

Now, back to chip BCIS3. 148 patients will be randomized. One group gets BCI with MPLA, the other group without. 148 patients doesn't sound like a lot, but the event rates are likely to be high. What's more, the end point of death, stroke, MI, C V hospitalization or periprocedural MI will be analyzed in a hierarchical way with the win ratio, this will likely catch most of the important outcomes. The mistakes of this trial are massive because it could overturn a common practice.

If the trial results are null, proponents might want to question the external validity of the trial. In other words, they might say, hey, did the sickest patients uh not get enrolled. We'll have to wait for the presentation. But I went and looked at the protocol paper. And boy, it suggests pretty strict criteria for what is high risk.

And to me, these things look like high-risk scenarios. Okay, consider what the entry criteria were. A BCIS jeopardy score greater than eight and LB dysfunction and a complex PCI. with either unprotected left main in the presence of an occluded dominant right or left dominant circulation, or disease involving the bifurcation or intended calcific calcium modification in multiple vessels or the left man or the final patent conduit.

or a target vessel as a C as a CTO with a planned retrograde approach. All of those to me, I'm just an outside observer, sound like pretty scary high risk situations. All right, champion AF. I spoke a lot about this last week, but I'll just be brief. This is Watchman versus Doak in patients with AF. It's an important trial because it looks to expand the indication for appendage closure.

The current guidance is to consider appendage closure in patients who either cannot take oral anticoagulation or have a reason not to take long term oral anticoagulation, which is very much stretched in the real world. Of course, this type of patient who cannot take anticoagulation was excluded from the trials. Champion specifically says it is studying patients eligible to take long term doex.

Boston Scientific sponsored the study and Boston Scientific representatives were brought uh lunch to my office this week. Yes, before the trial there were reps there handing out preprinted documents. And at the pre printed documents had the trial endpoints and it had this phrase on top quote, Is your practice ready?

As I said this week, this trial was designed to be positive before the first patient was enrolled, simply by the choice of the endpoints, the efficacy endpoint, tested for non-inferiority, stroke, systemic embolism, and CV death. The two problems, as I've written before, are C V death is not affected by either strategy, DOEC or

appendage closure. So it just adds noise, more events in both groups, and it makes non-inferiority easier to reach because no difference is a positive outcome in a non-inferiority trial. The second problem is the expected event rate is high at 12%, and this is used to set the non-inferiority margin of 4.8% absolute risk difference. That corresponds to a relative risk increase of 1.4 or 40% worse. However,

The champion authors do not have a non-inferiority margin for relative risk. Why is that important? It's important because if events are lower than expected, then applying a 4.8 absolute margin will allow for a much larger relative risk margin. So here's what to look at.

you look at the primary outcome relative risk point estimate and the upper bound. Does that upper bound exceed one point four? If it does, And had the designers insisted on an non-inferiority margin with both absolute and relative cutoffs. then the efficacy endpoint would not meet non inferiority. For the record, the prevailed trial, the seminal trial, had both an absolute and relative cutoff for non inferiority margin.

Okay, the primary safety endpoint is also highly likely to be positive because champion authors, like the option authors, exclude procedural bleeding. And I just showed you a study in JAMA cardiology which documents a huge upfront risk of major bleeding from the procedure. But that's not the only problem with this primary safety endpoint. The other component of it is non-major bleeds. And we know from the option trial and common sense and clinical practice.

that things like bruising and gum bleeds and non-major bleeding will be reported at a higher rate in patients who take anticoagulant. The secondary endpoint of all major bleeding is the endpoint to look at for the true safety. Here, you want to know the major bleeding, all major bleeding in both arms. But it the authors will test it with for non-inferiority. That's not the right test. You want this to be tested for superiority. So the question you want to ask is.

If we accept some d diminishing of efficacy, the non-inferiority margin for efficacy. we would want this to be safer, not just safe as, but safer. So this secondary endpoint, which is the true primary safety endpoint, should be tested for superiority. Instead it'll be tested for non-inferiority and it will likely reach non-inferiority. But you want to know, is it better?

All right, next is Orbita CTO. So chronic total occlusion PCI. is commonly done. It's complex, carries substantial risk, it's costly. Two RCTs of CTOPCI versus tablets have shown no difference in outcomes. One of the trials suggested a quality of life benefit. But of course any trial of a procedure versus tablet and that measures subjective outcomes is about useless because of placebo effect.

This weekend we get to hear about yet another Orbita placebo controlled trial. This will be CTO PCI versus placebo CTO PCI. And of course it comes from the UK. These orbit investigators have added so much to the knowledge of cardiology. Again, it's yet another trial designed to answer a true scientific question.

And it's a pretty simple design, right? Select patients with amenable CTO, stabilize them on medicines, stop the medicines before the procedure, and then do real PCI versus sham PCI and measure the subjective outcomes afterwards. Like the chip BCIS3 trial, this trial has huge implications for the field. Because CTOPCI is costly, risky, and does not reduce outcomes, its only reason for existence is symptom relief.

And if the placebo controlled effect in this trial is minimal to none, we may have reversed yet another common practice. As I wrote in my preview column, I suspect the effect on Angina will be modest. I think it'll be positive. But I don't know I don't know that it will be positive. It might not. We shall see. The one question I have is the decision to do this trial more like Orbita two than Orbita one. They will stop medicines so as to isolate the pure effect of CTO PCI.

But I wonder, what would it have been if the design was more like Orbita One, where they tested the incremental angina benefit over medical therapy? All right, next important trial, Spirit HS. Thank goodness that German investigators have tried repeating the Topcat trial of spiritolectone versus placebo in patients with FPF or uh heart failure with m uh minimally reduced EF.

Most of us know about the problems with Topcat, where half the patients did not get spirinolactone and had negative results. I've always considered Topcat a positive trial because if you consider the 50% of the trial where patients actually received the drug, there was a significant 18% reduction in heart failure hospitalizations and CV deaths.

And this will be the Spirit HF trial. Does spernolectone reduce hospitalizations for heart failure and CV death in modern day patients who have heart failure and an EF greater than forty percent? Now we know from the fine arts uh to trial that the MRA drug phenerinone reduces outcomes. but I strongly suspect that generic old fashioned spirlectone will as well.

like it did in the America's only subgroup of Topcat. Spirit HF is a hugely important trial for our field. Now some others that I did not highlight in my column because I can't write more than 1200 words because no one reads more than 1200 words. Alright, here's high petheo. This is a trial of ultrasound facilitated catheter directed fibrinolysis for acute PE.

This is a one-to-one randomization of patients with intermediate risk PE who also have two other indicators of cardiorespiratory distress such as soft blood pressure, high heart rate, or high respiratory rate. The primary outcome is a composite of PE related death, cardiorespiratory decompensation, or collapse or recurrent PE in a week.

I'm glad there will be studies of interventional PE because it's a bit like cerebral protection devices for Taver, isn't it? A cerebral protection device for Taverist ought to work because it catches debris. The picture is amazing. But actually, it did not reduce stroke. It was pretty much negative. Invasive P therapies break up clot or suck out clot, and the images are dramatic. But we should also have empirical outcome evidence.

The trick in these trials is applying them to real life because you can bet that the trials are very selective in their enrollment. Alright, next trial is Smart Decision, another beta blocker withdrawal study after MI with normal EF. We have at least five of these studies plus meta-analysis. It's hard to believe that this South Korean trial will deliver different results, but we shall see.

How about Easy PAVE trial? This is an RCT from South Korea randomizing patients with established vascular disease to a target LDL of less than fifty-five versus less than seventy. This is a good thing to study, isn't it? Because the recent lipid guidelines include many flowcharts with different targets. But unlike the hypertension trials like a cord and sprint, which actually looked at trials, we don't really have much direct RCT evidence that one target is better than the other.

Easy Pave will measure a mace endpoint of CV death, MI, stroke, revascularization, or hospitalization for unstable angina. Here's the thing to look for. If it's positive, we need to look at the size of the effect and the driver of the effect because getting to a LDL less than 55 increases the work of being a patient. The question is, is it worth it?

And for that we need to look at the effect size and the of uh specific outcomes reduced. Pro TAVI is a Dutch led investigator initiated multi center trial comparing TAVI with or without routine pre procedural PCI in patients who have established CAD. Four hundred sixty six patients undergoing TAVI will be randomized one to one to a PCI or no PCI. Now their concomitant C A D is defined in the usual way, stenosis of seventy to ninety nine percent.

um and or at least one stenosis between forty and seventy but positive physiologic measurements. The primary endpoint is a composite of death, MI, stroke, bleeding, and it will be tested with non inferiority. That's reasonable in this case. I like the study question not only because it informs a specific situation here, but also what the results will say about preventive PCI in chronic stable CAD. To me

There are no scenarios where revascularization of stable CAD improves outcomes over medical therapy. Surely I would think it would be the same after TAVI, but we will see.

All right, during the last late breaking session, there's going to be three RCTs dealing with PCI of left main coronary artery disease, and there is a bunch of featured research with interesting but smaller questions. And ACC really looks I will be doing a fireside chat at Sunday, a one forty five to two forty five in room three thirty eight.

I will also be doing an Ask Me Anything at the Heart.org Metscape Cardiology Booth and the Expo. I'll see you in New Orleans if I can get through security screening. Until next week, this is John Mandrola from the Heart.org Medscape Cardiology. You're listening to This Week in Cardiology from Medscape Cardiology Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD.