Feb 27 2026 This Week in Cardiology

You're listening to This Week in Cardiology from org Medscape Cardiology. Any views expressed are the presentation. And do not necessarily reflect the views of WebMD. Hi everyone, this is John Mandrola from the Heart.org Medscape Cardiology, and this is this week in cardiology for february twenty seventh, twenty twenty six.

This week I had a superb listener note on CPR and DNR orders. Persons versus doctors preferences for statins, more on GLP one drugs, another left atrial appendage closure story, and some closing cautionary notes on PFAF ablation. First listener feedback. I did not think I would receive any feedback on my coverage of the JAMA letter on unilateral DNR orders from last week.

I was struck by the fact that Gemma published such clear thinking on the tension of seeking and writing DNR orders, but indeed I received a superb piece of feedback on the tension of getting DNR orders, and the letter came from New Zealand no less. To recap about the story, very briefly, in an ideal world, patients who have life limiting disease or diseases recognize it and do not wish to have CPR in the event of hemodynamic collapse.

there is alignment between patient preferences and best medical care. Yet there is not always such alignment. In some cases patients are so ill that they cannot meaningfully participate in complex decision making. So a unilateral DNR is then placed. So the translation here is that the doctor treats CPR as a non beneficial intervention and states that we will not do it.

Like we won't do an AVR or an AFib ablation. Now this can be extremely complex when such an order conflicts with the family's wishes. One of the points made in the original JAMA piece was that DNR orders were often not clearly written enough to know who or how the decision came to be made. Well New Zealand cardiologist and advanced care planning ad advocate, doctor Tammy Pegg, wrote to me to say she agreed with my assertion that CPR

should be viewed as another medical intervention, and therefore its benefit risk lies with the clinical team, not so much the patient and family. She wrote to me that you can no more demand CPR than you can a laparoscopic choleostectomy. doctor Pegg then highlighted the non specific language around DNR and CPR. And she went back and and sent me to the original description from doctor James Jude, who described CPR way back in nineteen sixty one.

as chest compressions and rescue breasts, and this was an intermediary measure in the treatment of sudden unexpected cardiac arrest for a very different hospital environment. Peg goes on to say due to safe anesthesia and urgent revascarization for acute MI, the rates of genuine cardiac arrest are falling. What's more, bedside defibrillation also nearly negates the need for intermediary chest compressions.

But but most CPR requiring events in the twenty-first century, she points out, arise from serious illness. with deterioration and activation of early warning scores. Here, some measures such as IV fluids and vasopressors could be deployed in the periarrest period to prevent death. And I think this is her most important comment, and I put it in bold language in the transcript, but here it is.

She writes, but our language conflates CPR and resuscitation. Resuscitation is a verb, not a noun. It is an intention, not a specific treatment. The authors talk about the need for unilateral DNR order to be updated for a change in a clinical condition. This is much more important with a non specific order. doctor Pegg asks Is it time the US evolves its DNR orders to a DNA CPR or do not attempt CPR?

Although CPR is never deployed in isolation from other resuscitative measures, other treatments commonly termed resuscitative may be deployed before CPR in the periarrest period. If CPR could be remembered as Jude described it, as only bridging chest compressions, and if a do not attempt CPR does not restrict access to other evidence-based interventions deployed appropriately, In the periarest period, however,

then maybe this would result in increased patient acceptance of these orders and reduce the requirements for unilateral decision making. She attached a six minute YouTube video on talking about C PR with a patient who has advanced cancer and it is brilliant. I hope you go to that link and listen. Then when you're listening to that six minute video, I hope you think, what is harder?

Navigating that conversation skillfully, or placing a TAVI valve, or doing an AFib ablation, or reading a cardiac MRI. My friends, I think we have it easy compared to those who help people navigate at end of life. Thank you, Dr. Pegg.

All right, the first topic and a really good paper. This was in Gemma Internal Medicine. It's a research letter. It discusses the public preferences for statin therapy. And these authors were interested in finding the smallest worthwhile difference that patience described. The paper comes from a team at the University of Tokyo.

Now, because many statin eligible patients are unwilling to take statins, these authors set out to survey US and Japanese adults on their willingness to take statins based on the expected risk reduction benefits versus burdens. Now these were only surveys using the benefits of HARM trade-off method. The supplement of the paper describes the process, and it begins with a visual explanation of baseline risk and risk reduction with statins.

such as things like a ten percent baseline risk goes to seven point five percent with statins because it's a twenty five percent reduction. Now after they took a lot of baseline characteristics and they did comprehension checks, the authors ultimately sought the smallest worthwhile difference SWD smallest worthwhile difference.

Which is a preference based measure representing the minimum absolute risk reduction an individual considers enough to justify treatment after they weigh the treatment burden. So SWD smallest worthwhile differences were assessed by an iterative question sequence using graphic illustrations under three hypothetical ten year ASCVD risk scores, a two percent. A ten percent and a twenty percent ten year risk.

The authors also calculated the proportion of people willing to take statins at their actual efficacy, approximately twenty five percent relative risk reduction per one per thirty eight point six one milligrams per deciliter reduction in LDL. So the results. They sampled about two hundred fifty US individuals and three hundred Japanese individuals. Starting with the low risk, the two percent risk, most individuals with declined statins, about sixty three to seventy five percent

uh would decline even if statin reduced AC ASCVD risk to zero. At a ten percent risk at ten years, Forty two percent of the group would be unwilling to take statins, even if they reduced mace risk to zero. At twenty percent risk, it was still more than I expected. Twenty three in percent in the US, thirty eight percent in Japan would not take statins, even if they got a risk to zero. So the median SWD smallest worthwhile difference.

was seven point five percent in both countries at a ten percent risk. Now recall that statins reduce r risk by two point five percent at ten years. So because twenty five percent relative risk reduction of ten percent is two point five percent. The median s smallest worthwhile difference at a twenty percent estimated risk.

was ten to twelve point five percent in the US and Japan respectively. That's larger than the actual risk reduction from statins, which is twenty five percent times twenty percent was five percent. Now the proportion of these individuals willing to take statins at the current efficacy in the US was thirteen point eight percent and twenty three point six percent and thirty four percent at low, moderate, and high baseline risk. And it was mostly similar in Japan.

So the authors of this super interesting paper concluded quote although willingness increased with baseline risks, fewer than one third would initiate statins at actual efficacy at thresholds commonly used in guidelines. Revealing discrepancies between patient and specialist perspectives. My comments. I love this paper. While it's a relatively small sample, I think it's a wake-up call to guideline writers and prevention experts.

Our profession likes to go on about the specifics of when to take statins, how to use risk scores, adding coronary artery calcium to better quantify the risk, and yet this well done paper shows that none of that really matters to large groups of people. Methodologically, the choice to educate people, then check their comprehension before eliciting the smallest worthwhile difference is an excellent idea, because you can't accurately assess preferences unless patients know the facts, right?

Shocking here was that nearly one in four individuals would refuse stands even if they could get risk reduction from twenty percent to zero. Shocking also was that the smallest worthwhile difference for patients is essentially three times more than the actual risk reduction.

Now Andrew Foy has long taught me the concept that patients are minimizers and maximizers. The maximizers they're gonna do everything they can to reduce risk. They'll take statins, they'll take acetomibes, they'll do whatever. They might take stands at a two percent risk to get to zero percent risk. But what this paper shows is that most people tend to be minimizers. They want a lot more for bang for their buck in risk reduction if they're going to accept a daily statin.

Now, imagine my scenario that I like to talk about of putting statins over the counter. You put the statins in the uh in the pharmacy, you put a risk calculator in that aisle. If we did this and this group's finding was replicated. I think a lot fewer people would be taking statins than the Go look at this paper. First author is Lou L U O Jam Internal Medicine. It's an eye opener, but an important one because our patients are not automatons that do exactly what we recommend.

And finally, one final comment on the tension of decision support tools and uptake of recommended meds. The irony here is that these individuals were basically given Uber decision support. They were well educated. Then they were tested on it. They knew the data. And now in this educated state most were not willing to accept our profession's recommendation.

Now I could link to similar studies in anticoagulation that show similar things, that that is that when people really understand the absolute risk reduction, they often decline therapy because it's not enough for them.

All right, some GLP One news. Of course there's GLP One news. It's like every week. Lancet has published the Lidley sponsored Achieve Three Trial Comparing Efficacy and Safety of Orphoglypron, which is a new GLP drug from them against oral semaglutide in patients who have with type two diabetes who are inadequately controlled with metformin.

Some background. Oral semaglutide is currently the only orally administered GLP one receptor agonist approved for the management of type two diabetes, and it has additional indications for risk reductions in cardiovascular and chronic kidney disease. Or for glipron is Lily's GLP1, and it has the advantage of not requiring early morning administration with minimal water and then nothing by mouth for thirty minutes like or semaglutide has.

This was a fifty two week head to head comparison to assess non inferiority. of orphoglypron thirty six milligrams versus semaglutide fourteen and orphoglypron twelve versus semaglutide seven and the mean change uh at week fifty two from baseline hemoglobin A one C was the main uh endpoint. They also looked at other important secondary and s uh outcomes and safety measures. And reductions in hemoglobin A one C were numerically larger with orphoglypron at each dose compared to semaglutide.

For instance, at thirty six milligrams of orphoglypron versus semaglutide fourteen, it was one point nine one percent versus one point four seven percent reduction in hemoglobin A one C. These were both non inferior and superior statistically. Weight loss too was way better for orphoglipron, orphoglipron reduced risk. Weight thirty six milligram dose minus eight point two percent versus semaglutide fourteen, minus five point three percent, and roughly twice as many orphoglypron patients lost.

ten percent or more of body weight. The slight trade off though was more side effects, mostly GI with orphoglypron. Stopping the drug due to GI side effects was nine to ten percent for orphoglipron versus four to five percent semaglutide. Orphoglipron also had a three to four beat per minute increase in heart rate where it was only one to one point five beat per minute increase with semaglutide.

Now, I don't have much to say critically about this trial. It's sponsored by Lily, but I mean the comparisons and endpoints are pretty clear and objective. Having oral GLP1 drugs will allow more people to take them, and given the rise in diabetes and obesity and its relationship to AFib and hypertension and HEFPEF for that matter, these drugs will soon transition from being diabetes drugs to cardiac drugs. Much like the SGLT two inhibitor drugs did.

All right. A side note on GLP drugs is that there is actually a new trial, um, called the Seminole AF trial. This is actually testing whether Semaglutide will be an antiarhythmic drug. I received a nice email from doctor Peter Weiss saying He was an academic electrophysiologist from the University of Arizona who listened to the podcast. Thank you, Peter, and w wrote to notify me that they are now enrolling patients in a multi center trial

that is prospectively randomizing AFib patients, including those continuing with medical management, as well as those having ablation therapy to treatment with or without semaglutide. And there's actually placebo. It's the seminal AF trial and I I will provide the clinical trials dot gov link. The primary endpoint, get this everybody.

is time to AFib event. And that is awesome because I, like you, want to know if these drugs are actually antirhythmic drugs. They may be better than the standard anti-arrhythmic drugs.

Alright, next topic another left atrial appendage closure story. This has to do with the relationship between spontaneous echo contrast and outcomes after left atrial appendage closure. Jackie P has published this Japanese registry study where the authors separated about twelve hundred patients across twenty Japanese centers who had left atrial appendage closure with watchman devices.

into three categories based on their spontaneous echo contrast severity. Uh one c one category was no uh spontaneous echo contrast. Uh one was mild to moderate, which degraded uh spontaneous echocontrast one-two plus, and severe which was spontaneous echo contrast three to four plus.

Now, some quick background. Spontaneous echo contrast is sometimes called smoke. In patients with healthy left atriums, the LA chamber looks pitch black on a TE When the when there is LA structural and electrical disease with dilation, the echo images show this smoke like contrast, almost like those Christmas toys. That you can shake up and then see the snow. The cause of this is probably red blood cell aggregation due to low flow state.

Spontaneous echo contrast is associated with caught formation and stroke, and obviously if there is such low flow in the entire left atrium, I know you are wondering the benefit of closing the left atrial appendage because that is only one. area clots can form in such an atrium. Alright, back to the study. About thirteen percent of the twelve hundred patients had severe spontaneous echo contrast.

The these patients also had other factors such as higher Chad's vast scores, larger left atrial volume indices, lower appendage emptying velocities, and a greater prevalence of cauliflower type appendage morphology, supporting the concept. that several clinical and anatomic features may collectively define the baseline risk for thromboembolism.

The results of this paper are quite sobering indeed, and Patients with severe spontaneous echo contrast experienced a greater Two year cumulative incidence of ischemic stroke, TIA or systemic embolism, eleven point five percent, eleven point five percent compared with those without spontaneous echo contrast, four point four percent or mild to moderate five point four percent.

Likewise, device-related thrombus, DRT, occurred in sit down and get off the bike for this. 12.4% of patients with severe spontaneous echo contrast. versus two point eight percent of those without spontaneous echo contrast. Pause there, said

That is more than one in ten patients with severe spontaneous echocontrast who had DRT, and DRT is a terrible outcome. It's basically a failure of of left atrial appendage closure because it increases the risk of stroke up to fourfold and it requires oral anticoagulation to treat, which is what the left atrial appendage closure device is supposed to replace.

Now, they did multivariate analysis and they found that severe spontaneous echocontrast was not an independent predictor of ischemic events, but remained significantly associated with an increased risk of DRT, device related thrombus. Now the authors did something smart. They also looked at the role of the types of atrial fibrillation, particularly non paroxysmal or basically permanent AFib, and that seemed to matter.

When spontaneous echo contrast grade was combined with AFib type, patients with severe spontaneous echocontrast and non-paroxysmal AFib had nearly threefold higher adjusted risk for both thromboembolism and DRT. Now my comments there's an excellent editorial from doctors Magno Cavallo and Della Rocca who emphasized The spontaneous echo contrast is not just an imaging thing, but instead a marker of severe effective

Atrial myopathy. Let me quote them specifically. They write in the race towards procedural innovation, it is easy to view left atrial appendage. Closure as a mechanical solution to a mechanical problem. Yet, this ocean left atrial appendage closure data remind us that the stroke prevention in atrial fibrillation remains.

functionally a problem of atrial disease biology. And I could not agree more with that statement. And this, my friends, is the existential problem for left atrial pendage closure as a treatment strategy. Now consider the difference between what we do in cardiology with this procedure versus what the surgeons did in Laos three.

In the surgical trial, they started with the fact that AF is a systemic disease and stroke does not only come from one of Verkau's triad stasis, but rather AF has associated Prothrombotic blood components and endothelial factors. Therefore, the Laos III strategy was to continue anticoagulation and ask whether closure of the appendage provides additional additive benefit, and it did.

Stroke was reduced on top of the inecoagulation therapy, which takes care of the prothrombiotic blood components and endothelial parts of s of stroke risk. But but we in cardiology think way more simplistically. We hew to the Cartesian idea that humans are just like machines that can be tweaked

So clots are often seen in an appendage so it should be closed, and then we can stop anticoagulation. That strategy dismisses all the other benefits of anticoagulation therapy outside of preventing clots in one corner of the body. The important observation from the Japanese team reminds us that stroke in patients with AFib is far more complex.

than just the left atrial appendage. Of course it has always been the case, but here We see that patients who have bad left atrial disease, as manifested by smoke or a spontaneous echo contrast, do terrible with left atrial appendage occlusion, especially if they have permanent forms of AF. A DRT rate of twelve percent, if confirmed, should basically stop appendage closure in these patients, because they're gonna have to remain on oral anticoagulation.

And of course this is the question being studied in the Layos four trial that the PHRI people in Canada are asking. They're gonna ask in Layos four Can catheter based appendage occlusion prevent ischemic stroke or systemic embolism in patients with AF who remain at high risk of stroke despite already receiving

oral anticoagulation. And LayOS four will recruit patients with permanent AFib and high stroke risk, and I'm sure there will be a fair number of patients in that trial who have spontaneous echo contrast on T E. I also think this paper has direct importance to our clinical practice. I have said and multiple observational papers have shown that U.S. doctors are doing appendage closure in patients who have higher comorbidity than those in the seminal trials, older patients, sicker patients.

And this paper is yet another suggesting that this is an unwise choice because if your eighty year old patient with permanent AFib has spontaneous echo contrast, I would resist the urge to do appendage closure. Do that patient a favor and just do anticoagulation until you re learn the results of Layos four.

All right, I wanna close and I'm gonna have some concluding remarks on my talk here at Western AFib in Utah. I don't usually do this and I won't make a habit of it, but I'm in Salt Lake City, Utah for Western AFib. And by the way Uh this is about as close to the US comes to Switzerland for beauty. The bright sun and the snow covered mountains and clean air here is truly one of the United States' most epic places.

The lecture I was assigned to give by my friend Nasir Maruj, one of the nicest people in EP is will go off at about two PM Eastern Standard Time, approximately three hours before this podcast post. The title New Toys in AFib Separating Evidence from Enthusiasm. So this made me think What new toys have tons of enthusiasm, but not so much convincing data? And so I chose to start with PFA. Why? Because I have trouble controlling my own enthusiasm for this amazing technology.

In clinic, I tell patients how much better AF ablation is now. It's faster, there's less inflammation, less chest pain, there's less risk of catastrophic AE fistula and death. We can ablate inside the veins and that we don't worry about PV stenosis. The catheter that I use mostly is a nine millimeter catheter, which is three times the size of a three millimeter RF catheter.

Each delivery is four seconds instead of ten to twelve seconds. I mean it takes longer to put the patient on general anesthesia and and put patches on the patient than it does to do the procedure itself. I mean two weeks ago I did six PFAA fib oblations in one day I was done before uh four o'clock and I wasn't rushing. But for the talk I put on my science hat and I realized that when you really do that

Maybe this enthusiasm for PFA is outstripping the evidence. And I came up with five enthusiasm reducers. I was really nervous to present these at Western AFib. This is an audience of believers. There's a lot of industry here. I was hesitant to tell you all about these five areas of uh worry that I have with PFA.

But then but then as I finalized my slides last night, I went to the hotel gym for a little ride before dinner. I like to ride before dinner. Nothing hard, just two hundred watts for forty five minutes. Well, in the gym I met one of the world's most thoughtful EP doctors, who's a friend, and we hugged. And then he told me, without me asking, that he was writing a highly critical piece about PFA.

And then he went through the points, and it was as if he was spying on my cuter computer because his points were nearly the same as mine. So then I thought, if one of the most thoughtful people in EP thought these things, I will tell them to you, and I'll present them to the Western AFib audience. So here what I here are what I call the enthusiasm reducers for PFA. Number one. There's a lack of superiority over thermal ablation.

PFA is simply not much better than RF or Cryo Balloon. I know the single shot champion trial in Switzerland was it was a little better, but when you take the totality of the evidence, it's not much different. Number two. PFA gives us the ability to unthinkingly destroy myocardium, so much so that it can lead to hemolysis and acute kidney injury. We never had to worry about shredding red blood cells before.

And now number three, there are reports of late unexplainable sudden cardiac death. A report from German authors, first author Melanie Gunwardin, from Frankfurt, Germany, Where they describe eleven patients who had late malignant arrhythmias, including five patients with STEMI, two with VF in the procedure, and two deaths, deaths, one in three days and the other twenty two days.

That the death at day three was due to an acute RCA occlusion without any atherosclerosis, thus suggesting a late coronary vasospath. So my question is, are we trading the one in a thousand risk for A fistula for a similar risk of sudden death from MI? Fourth top fourth problem with PFA is its cost. It costs three times more than standard RF. And in US most people are uh dissociated from cost. But what if you weren't? What if you were paying?

Would a PFA catheter be worth three times more? I'm asking. And finally, the number five thing that I worry about with PFA, and this may be the most important, my friend Pietor Futima in Poland and I have discussed this multiple times. We have discussed that PFA is destroying the thinking part of EP. I mean people used to think of us, the EP docs, as the smart docs, but now we may be creating a generation of unthinking left atrial bombers.

I used to say PFA has done nothing to advance our knowledge of AF, but after a year of doing this and seeing what I'm seeing, I wonder if PFA isn't diminishing our knowledge. Now two other new toys that I talked about that are outstripping enthusiasm are Zero Floral Ablation and concominant left atrial appendage closure at the time of ablation. And you've heard my critique of option, but the Western AFib audience hasn't.

and I will present it to them. Option trial, maybe one of the most biased trials ever done in electrophysiology. Okay, so that's it for this week in cardiology for one of the United States most beautiful areas. And remember, if you like this podcast, please take the time. To give us a rating or write us a review. And if you have feedback, please write to me. I'm learning a ton from these and I really enjoy it. Until next week, this is John Mandrola from the Heart.org Metscape Cardiology.

Heart. org Medscape Cardiology.