Feb 27 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. Any views expressed are the presenter's own and do [music] 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 27th, 2026. This week, I had a superb listener note on CPR and DNR orders, persons versus doctor's preferences for statins, more on GLP1 drugs, another left atrial appendage closure story, and some closing cautionary notes on PFA AF ablation. First, listener feedback. I

0:48 did not think I would receive any feedback on my coverage of the JAMAMA letter on unilateral DNR orders from last week. I was struck by the fact that JAMAMA 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 lifelimiting 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

1:34 participate in complex decisionmaking. 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 AIB 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 JAMAMA 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 advocate Dr. Tammy Peg wrote to me to say she agreed with my assertion that CPR should be viewed as

2:19 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 choleaccystectomy. Dr. Peg then highlighted the non-specific language around DNR and CPR. And she went back and and sent me to the original description from Dr. James Jude who described CPR way back in 1961 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 revascularization

3:04 for acute MI, the rates of genuine cardiac arrest are falling. What's more, bedside defibrillation nearly negates the need for intermediary chest compressions. But but most CPR requiring events in the 21st 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 Perry arrest 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

3:51 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. Dr. Peg 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 Perry arrest period. If CPR could be remembered as Jude described it as only bridging chest compressions and if a do not attempt CPR

4:36 does not restrict access to other evidence-based interventions deployed appropriately in the Perry arrest period, then maybe this would result in increased patient acceptance of these orders and reduce the requirements for unilateral decisionmaking. She attached a six-inute YouTube video on talking about CPR 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-inute video, I hope you think what is harder navigating that conversation skillfully or placing a tavy valve or doing an AIB 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. Peg.

5:23 All right, the first topic and a really good paper. This was in JAMAMA 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 patients described. The paper comes from a team at the University of Tokyo. Now, because many statinel 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 benefit harm trade-off method. The supplement of the paper describes the process and it begins with a visual

6:09 explanation of baseline risk and risk reduction with statins such as things like a 10% baseline risk goes to 7.5% with statins because it's a 25% 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 burdens. So, SWD's smallest worthwhile differences were assessed by an iterative question sequence using graphic illustrations under three hypothetical 10-year ASCVD risk scores,

6:54 a 2%, a 10%, and a 20% 10-year risk. The authors also calculated the proportion of people willing to take statins at their actual efficacy, approximately 25% relative risk reduction per one per 38.61 61 mg per deciliter reduction in LDL. So the results they sampled about 250 US individuals and 300 Japanese individuals. Starting with the low risk, the 2% risk, most individuals would decline statins about 63 to 75% uh would decline even if statin reduced a ASCVD risk to zero. At a 10% risk at 10 years, 42% of the group would be unwilling to take statins. Even if they reduced mace risk to zero at 20% risk,

7:44 it was still more than I expected. 23 and% in the US, 38% in Japan would not take statins. Even if they got a risk to zero. So the median SWD smallest worthwhile difference was 7.5% in both countries at a 10% risk. Now recall that statins reduce risk by 2.5% at 10 years. So because 25% relative risk reduction of 10% is 2.5%. The median smallest worthwhile difference at a 20% estimated risk was 10 to 12.5% in the US and Japan respectively. That's larger than the actual risk reduction from statins which is 25% times 20% was 5%. Now the

8:32 proportion of these individuals willing to take statins at the current efficacy in the US was 13.8% and 23.6% 6% and 34% 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 onethird 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 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

9:18 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 statins even if they could get risk reduction from 20% 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

10:04 patients are minimizers and maximizers. The maximizers, they're going to do everything they can to reduce risk. They'll take statins, they'll take a zetto, they'll do whatever. They might take statins at a 2% risk to get to 0% 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. Go look at this paper. First author is Lou Lo Jam internal medicine.

10:51 It's an eye openener 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 anti-coagulation 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 GLP1 news. Of course,

11:38 there's GLP1 news. It's like every week. Lancet has published the Lily sponsored achieve three trial comparing efficacy and safety of orphoglyphron orphoglyphron which is a new GLP drug from them against oral semaglutide in patients with type 2 diabetes who are inadequately controlled with metformin. Some background, oral simaglutide is currently the only orally administered GLP-1 receptor agonist approved for the management of type 2 diabetes and it has additional indications for risk reductions in cardiovascular and chronic kidney disease. Or for glyphron is Lily's GLP1 and it has the advantage of not requiring early morning administration with minimal water and then nothing by mouth for 30

12:24 minutes like semaglutide has. This was a 52- week head-to-head comparison to assess non-inferiority of orphoglyphron 36 milligrams versus hemoglutide 14 and orphoglypherron 12 versus semlutide 7 and the mean change uh at week 52 from baseline hemoglobin A1C was the main uh endpoint. They also looked at other important secondary and uh outcomes and safety measures and reductions in hemoglobin A1C were numerically larger with orphoglyphron at each dose compared to semaglutide. For instance, at 36 milligrams of orphaglyron versus semlutide 14, it was 1.91% versus 1.47% reduction in

13:10 hemoglobin A1C. These were both non-inferior and superior statistically. Weight loss 2 was way better for orphaglyron. Orphagon reduced weight 36 milligram dose minus 8.2% versus semaglutide 14 minus 5.3% and roughly twice as many orphoglypherron patients lost 10% or more of body weight. The slight trade-off though was more side effects mostly GI with orphoglyphron. Stopping the drug due to GI side effects was 9 to 10% for orphaglipron versus 4 to 5% semaglutide. Orphoglyphron also had a 3 to four beat per minute increase in heart rate where it was only 1 to 1.5 beat per minute increase with semiglutide.

13:57 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 GLP-1 drugs will allow more people to take them. And given the rise in diabetes and obesity and its relationship to aphib and hypertension and hep for that matter, these drugs will soon transition from being diabetes drugs to cardiac drugs much like the SGLT2 inhibitor drugs did. All right, a side note on GLP drugs is that there is actually a new trial um called the seinal AF trial. This is actually testing whether semaglutide will be an antiythmic drug. I received a nice email from Dr. Peter Weiss. He was

14:42 an academic electrophysiologist from the University of Arizona who listened to the podcast. Thank you, Peter. and wrote to notify me that they are now enrolling patients in a multic-center trial that is prospectively randomizing aphib 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 will provide the clinicaltrials.gov gov link. The primary endpoint, get this everybody, is time to AIB event. And that is awesome because I like you want to know if these drugs are actually anti-arismic drugs. They may be better than the standard anti-arismic drugs. All right, next topic. Another

15:28 left atrial appendage closure story. This 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 author separated about 1,200 patients across 20 Japanese centers who had left atrial appendage closure with watchman devices into three categories based on their spontaneous echo contrast severity. uh one one category was no uh spontaneous echo contrast. Uh one was mild to moderate which they graded spontaneous echo contrast 1-2 plus and severe which was spontaneous echo contrast 3 to 4 plus. Now some quick background spontaneous echo contrast is

16:16 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 lowflow state. Spontane echo contrast is associated with clot 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. All right, back to the study. About 13% of the,200 patients had severe

17:03 spontaneous echo contrast. 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 throbo emolism. The results of this paper are quite sobering indeed. Patients with severe spontaneous echo contrast experienced a greater two-year cumulative incidence of eskeemic stroke TIA or systemic embolism 11.5% 11.5% compared with those without spontaneous echo contrast 4.4% or mild to moderate 5.4%.

17:50 Likewise device related thrombus DRT occurred in sit down and get off the bike for this 12.4 4% of patients with severe spontaneous echo contrast versus 2.8% of those without spontaneous echo contrast. Pause there. That is more than 1 in 10 patients with severe spontaneous echo contrast who had DRT. And DRT is a terrible outcome. It's basically a failure of left atrial appendage closure because it increases the risk of stroke up to four-fold and it requires oral anti-coagulation 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 echo contrast

18:35 was not an independent predictor of eskeemic events but remains 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 fi fibrillation particularly non-paroxismal or basically permanent aphib and that seemed to matter when spontaneous echo contrast grade was combined with aphib type. Patients with severe spontaneous echo contrast and non-paroxismal aphib had nearly threefold higher adjusted risk for both throbo emolism and DRT. Now my comments there is an excellent editorial from doctors Magno Cavalo and

19:22 Delaroka who emphasize the spontaneous echo contrast is not just an imaging thing but instead a marker of severe atrialopathy. Let me quote them specifically. They write, quote, "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 and 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 pendance closure as a treatment strategy. Now consider the difference

20:07 between what we do in cardiology with this procedure versus what the surgeons did in Laos 3. In the surgical trial, they started with the fact that AF is a systemic disease and stroke does not only come from one of Verkow's triads, stasis, but rather AF has associated prothrombotic blood components and endothelial factors. Therefore, the Laos 3 strategy was to continue anti-coagulation and ask whether closure of the appendage provides additional additive benefit and it did. stroke was reduced on top of the anti-coagulation therapy which takes care of the prothrombotic blood components and endothelial parts of of stroke risk. But but we in cardiology

20:55 think way more simplistically. We hue to the cartisian 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 anti-coagulation. That strategy dismisses all the other benefits of anti-coagulation 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 aphib 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 12% if confirmed

21:43 should basically stop appendage closure in these patients because they're going to have to remain on oral anti-coagulation. And of course, this is the question being studied in the Laos 4 trial that the PHRI people in Canada are asking. They're going to ask in Laos 4, can catheter-based appendage occlusion prevent es schemic stroke or systemic embolism in patients with AF who remain at high risk of stroke despite already receiving oral anti-coagulation. And Laos 4 will recruit patients with permanent AIB 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 TE. I also think this paper has direct importance to our clinical practice. I have said in multiple observational

22:29 papers have shown that US doctors are doing appendage closure in patients who have higher coorbidity 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 80year-old patient with permanent AIB has spontaneous echo contrast, I would resist the urge to do appendage closure. Do that patient a favor and just do anti-coagulation until you relearn the results of Laos 4. All right, I want to close and I'm going to have some concluding remarks on my talk here at Western AIB 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 Apheibb. And by the way, uh this is about as close to the US

23:18 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 Marouch, one of the nicest people in EP, will go off at about 2 p.m. Eastern Standard Time, approximately 3 hours before this podcast post. The title, New Toys in Aphib, 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

24:04 ablation is now. It's faster. There's less inflammation, less chest pain, there's less risk of catastrophic aefistula 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 9mm catheter, which is three times the size of a 3mm RF catheter. Each delivery is 4 seconds instead of 10 to 12 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 PFAB ablations in one day. I was done before uh 4:00 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

24:50 for PFA is outstripping the evidence and I came up with five enthusiasm reducers. I was really nervous to present these at Western AIB. 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 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 200 watts for 45 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

25:36 through the points and it was as if he was spying on my computer 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 AIB 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 cryob balloon. I know the singleshot champion trial in Switzerland where 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 myioardium. So much so that it can lead

26:21 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 Ganowardin from Frankfurt, Germany, where they describe 11 patients who had late malignant arhythmias including five patients with STEMI, two with VF in the procedure and two deaths deaths one at three days and the other 22 days that the death at day three was due to an acute RCA occlusion without any atheroscerosis thus suggesting a late coronary vasospasm. So my question is are we trading the one in a thousand risk for a fisticula for a

27:08 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 Ptor 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

27:54 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 aphib audience hasn't, and I will present it to them. option trial may be 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

28:41 write to me. I'm learning a ton from these and I really enjoy it. Until next week, this is John Mandola from the heart.org or Medscape Cardiology. >> You're listening to this week in cardiology [music] from theheart.org. Medscape Cardiology. This podcast is intended for health care professionals only. Any views expressed are the presenter's [music] own and do not necessarily reflect the views of WebMD or Medscape.