July 24 2026 This Week in Cardiology

You're listening to this week in Cardiology from the Heart.org MedScape Cardiology. This podcast is intended for healthcare professionals only. Any views expressed are the presenters' own and do not necessarily reflect the views of WebMD or MedScape. When every decision matters, you need trusted medical intelligence. MedScape AI synthesizes peer-reviewed evidence and MedScape's expert validated content in seconds, delivering clinically verified answers you can trust. Even over 13 million MedScape members on the world's leading platform for clinicians 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 July 24th, 2026. This week, the first oral PCSK9 inhibitor is approved. Another study finding safe MRI scanning in patients with non-conditional devices, the PFA sham trial, and the curious case of orthopedic injuries in Cardiology. The first story is enlistetide is approved. FDA has approved this first oral PCSK9 inhibitor enlistetide for hypercholesterolemia. The brand name will be LIPFendra. Expect free burritos in the office soon. This approval is based on a 3000 patient coral reef lipids RCT of enlistetide versus placebo where the oral PCSK9 inhibitor reduced LDL cholesterol by 57% and the coral reef hereditary familial hyperlipidemia trial where the reduction was 58% over placebo. Notably absent however, our trial showing that the new $310 per month drug reduces cardiovascular outcomes. Now we know that the injectable PCSK9 drugs which are monoclonal antibodies reduce CV outcomes in high risk post-MI patients and more recently in the Vesalius trial in patients without MI. But, but enlistetide is not a monoclonal antibody. It inhibits PCSK9 via a different mechanism. It's a macrocyclic peptide inhibitor. Now, cardiologist Dr. Greg Katz writes on his sub-stack and I'll link to it. While the drug reduces LDL cholesterol to the same degree as the injectables, we do not know whether it reduces CV outcomes. It probably reduces CV outcomes because LDL cholesterol is clearly causal in ASCVD. But there have been numerous stories of drugs that reduce lipid particles that do not reduce CV outcomes. And here's a quote from Dr. Katz. Quote. In 2006, Pfizer had a lipid drug called Torsetra bib. A drug from a class of medications called CTEP inhibitors that raised HDL and lowered LDL incredibly well. And the Pfizer CEO, at the time told investors it would be, quote, one of the most important compounds of our generation. Shortly after that statement, Pfizer killed the program when the outcomes trial showed a roughly 60% increase in deaths from on-off target of the fact that the cholesterol numbers gave no hint of. Now, the coral reef outcomes trial will test the drug's effect on MACE. It's currently completed in Roman of nearly 15,000 patients and the study completion date is 2029. So we won't know the actual effect size of the drug for the outcomes that we care about for three years. So I'm in agreement with Dr. Katz on this, while many of the key opinion leaders in cardiology have been quoted as being positive on the drug, I would wait for CV outcomes results. To be sure, I think the outcomes will be similar to the injectables, but we don't know for sure. I put myself down as 80% probability that it'll be similar to the Vaseleus and Odyssey results, but there'll be some small reduction in nonfatal cardiovascular outcomes. Now what's more, the drug is similar to oral semaglutide and that it has to be taken first thing in the morning and then nothing by mouth for 30 minutes. And that doesn't seem like a big deal, but it's yet another thing that increases the work of being a patient. So the next topic is MRI scans in non-conditional CIEDs or cardiovascular internal electrical devices basically pacemakers and defibrillators. Now these days, at my age, few things in medicine actually make me angry. I mean my trail name on the Appalachian Trail was friendly John, but one thing that consistently does make me angry sometimes mad enough to almost ruin my day is when a patient with a device cannot get an MRI because of sclerotic institutional policies. It just drives me bananas. I was actually a co-author on the 2017 HRS expert consensus document on MRI imaging in patients with devices. My section that I was responsible was for scanning of non-conditional devices. And while there are no RCTs in this space, there are numerous observational and descriptional studies that all show that it was safe to scan these patients as long as there was an institutional protocol. That paper was published in 2017 in heart rhythm and there's still to this day, nine years later, great variability in the availability of MRI scans and patients with cardiac devices. At some institutions, I'm told that they just scan everyone. At others, if you're not labeled conditional, there is no scan. Now while MRIs are surely overused, I have no doubt. There are clearly cases where imaging with MRI makes a huge difference in patient care. So a report in the journal Heart Rhythm 02 caught my eye. This was a small single-center report of only 28 mostly congenital heart patients with devices who had had an MRI. The main method around the problem with scanning these patients was to have a pediatric EP nurse practitioner basically be the champion for the MRI scan. And the nurse practitioners were all certified in EP and they did a lot. They determined the MRI compatibility and risk. They determined programming for the scan and provided patient rhythm monitoring for the non-conditional devices. They then provided pre-imposed MRI evaluation and programming of the conditional devices and full interrogation was completed prior to and immediately after the MRI. And with this program at the University of Michigan, here's a summary of the results. Epocardial pacemakers were seen in 53% of these patients. Transvenous pacemakers are ICD and 40% and a sub-QICD in two patients. Seven patients, 25% had abandoned leads. 18 devices were MRI non-conditional. That's 65%. So two-thirds of these patients were non-conditional. And remember, a quarter had abandoned leads. Get this. No patient. No patient had clinically significant change in lead parameters concerning a rhythmia or patient reported symptoms during the MRI scan. The median nurse practitioner time provided an MRI for a patient requiring continuous monitoring. That was 79% of them was 100 minutes, so a substantial investment. But in short, everyone did well. There were no major safety issues. Despite abandoned leads, pacer dependence, non-label devices, no patient was harmed. While I don't often comment on small, single-setter description studies, I do hear because this topic needs more attention. I've cited our 2017 consensus document. The first authors there were Julia Indick and Rod Gimbal, but I'll also point you to a systematic review and meta-analysis in the European Heart Journal published more recently, where the authors included 35 cohort studies of 5,625 device patients with non-conditional devices who had 7,100 MRI scans and paused there. More than 5,000 patients with non-conditional devices had MRIs. That alone is an important fact. Yes, fact. In the results of this paper, no deaths, zero. The rate of adverse events were small. Electrical reset 1.4%, symptom of heating or torque 0.7%. Inappropriate pacing, 0.37% in generator failure 0.14%. Significant increases in lead pacing threshold were seen in up to 1.1%, while P and R wave sensing reduction of greater than 50%, were seen in 1.5 and 0.4 respectively. Changes in pacing lead impingence of greater than 50 ohms are a high voltage lead impingence of greater than 3 ohms were noted in 4.8 and 0.4 respectively, while decreases in battery voltage of greater than 0.02 volts were seen in 2.2%. No patient had ICD shocks. So taken together, this meta-analysis affirms the safety of MRI imaging in non-conditional devices with a very low incidence of adverse events and non-significant changes in lead parameters. Of note, the evidence for MRI safety in patients with non-conditional devices was derived primarily from scanners of less than 1.5 Tesla. Notably all the included studies in this meta-analysis and this is an important point, disclosed strict programming and monitoring protocols during the MRI scanning procedure. In general, devices were programmed into asynchronous pacing, particularly in studies enrolling patient or monitor only for non-pacer dependent patient. Second, tacky arrhythmia therapies, including all anti-tactic cardiac pacing and shocks were turned off during the MRI scans. And the MRI procedures were supervised by either cardiac cardiologist or cardiac nurses who were trained in ACLS with experience in device programming. And patient monitoring included a minimum of an ECG and pulse oximetry. In other words, we're not talking about willing, nearly scanning at the outpatient MRI scanner in the suburbs. MRI scans can be safely done in nearly anyone with a device, but the caveat is that there has to be a required protocol of smart programming and surveillance. And in this Michigan study, a hundred minutes of nurse practitioner time. To me, an MRI scan in a non-conditional patient should be considered like any medical procedure. There are benefits and harms. The job of clinicians is to assess this calculus and what is best for the patient. And by saying clinicians, I include radiologists who as doctors, yes, radiologists or doctors must consider the patient's clinical scenario as much as the ordering clinician. The paper I describe from Michigan used trained EP nurse practitioners. I know that some academic centers use cardiac fellows. But whatever the mechanism is for monitoring and programming in 2026 where you can take a driverless car in some cities, we should be able to scan patients with non-conditional devices when the benefit harm balance is favorable. That this is a problem in many places boggles my mind and actually has the ability to make me angry. I just don't know how to change it, but it needs to change. This perhaps is a role for our professional societies. Alright, third topic is one that I missed. And this is the PFA sham trial. The PFA was a dual center in the Czech Republic. Sham controls single blind patients were single-blinded. In 60 patients comparing PFA a fifth of ablation against the sham procedure in patients with highly symptomatic AF. All patients had loop recorders. The six month co-primary outcomes were A. Time to first recurrence of atrial tachyrythmia and B. Changes from baseline in the AFib effect on quality of life's score. The trial procedures were that all 60 patients had an EP study to exclude an accessory pathway or some other SVT. One group got a PFA and the other group got deep insidation for about the same time as it took the due PFA and then had figure of eight stitches in the femoral vein access. Most patients in this trial had P-A-F, paroxysmal AF, only 23% had persistent AFib and cardioversion during the EP study was done in only 15%. This is an important detail because in the British sham PVI trial, which was published two years ago, 79% of those patients had persistent AFib and cardioversion was done in almost all of them. As both trials were short and follow up, you could imagine that a cardioversion may hold for a short time and that would reduce the benefits of ablation. In PFA sham, cardioversion was being done in so few patients. It means the control arm, I think, was a lot stricter. Now the key results in PFA sham were markedly positive. Freedom from arrhythmia, 93% of patients in PFA versus 17% in sham. You don't need statistics for that. The AFib questionnaire improved by 44 points versus 11 points and in that 32.6% between group difference also doesn't need statistics. It's obviously positive. The secondary endpoints where AF burden and the median was zero in the PFR-ARM versus zero point four three in the sham arm and an anxiety scale also favored the PFA arm. When you look at AF burden, it really is remarkable. Zero median in the PFA arm versus zero point four three in the sham arm. The sham arm ranged from a zero point zero four to three point four seven. Even in those patients, the median was pretty low burden. The authors rightly concluded that PFA was superior to sham and reducing arrhythmia recurrences and AF burden and in improving the quality of life and AF associated psychological distress. In doing so, this PFA sham trial confirmed the results of the British PVI trial published back in 2024 and JAMA. In my comments, I'm glad that we have two sham control trials. While I have long called for such trials, I've always felt the probability was very high that there would be a placebo resistant effect in AFiblation. But this trial, like the sham PVI, has some important limitations and we should just discuss them, not as a criticism of the authors, but as a critical appraisal of the study. Number one, this is a small study in two centers with only 30 patients per arm and there's wide credible intervals. The follow-up was only six months. There was imperfect blinding as noted in the bang, James blinding in the season these papers. Unlike sham trials in coronary stentings, blinding in AFiblation is tough because of the easy availability of consumer rhythm devices. Even a blood pressure cuff can tell you if you have any irregular rhythm and so this is no knock on the authors. It's just hard to do blinding in AFiblation studies. Another important and I think more important limitation was the selection of highly symptomatic PAF patients. This is the group I am least worried would have a predominantly placebo effect from AFiblation. The group that I think is most susceptible to placebo effect from an AFiblation is the obese patient who's minimally mobile and he or she has persistent A5. Many of these patients come to me and they have persistent A5. Maybe it's been diagnosed in a primary care office, maybe at a pre-op ECG. Medicare wellness visit for instance and they're found to be an AFib. The doctor tells them so and then the patient says, "Well yeah, I'm fatigued and tired and a doctor wants to do AFiblation." These patients, the correlation between symptoms and rhythm is one of the most difficult calls in modern electrophysiology I think. People with severe cardiometabolic disease have fatigue and low power with or without AFib. So it's really hard to tell. Now I suspect that the high cardiovirgin rate due to persistent A5 is likely why the quality of life differences were a lot less than the sham PVI trial than they were in the PFA sham trial. Finally, I realize this is nitpicking but both the sham trials had very weak sham procedures. A proper sham would include a transceptal heart catheterization because the act of doing the transceptal, the atrial septal puncture may enhance the placebo effect via autonomic or hemodynamic means. Now I realize why this is not done. It's not done to enhance patient safety. I get that, really. But scientifically a stronger sham would enhance our confidence in the results. What said, as I, in you expected, AFiblation, especially when done in highly symptomatic paroxysmal A5 patients likely has a strong placebo-resistant effect? Now thank goodness we've found this since we've been doing this procedure for two decades and imagine if we were fooled. Speaking of being fooled, I want to speak about a medscape news article, what will it take to make floraoscopy lab safer as the title? And this was a document in Jack intervention. It was an expert consensus document and it was done for many societies on enhanced radiation protection in the, a cath and EP lab. Now the background here is obvious, right? Cardiology uses X-ray in our procedures. Cardiologists are exposed to lots of X-rays over the course of a lifetime. And efforts to reduce that exposure are laudable and no one is against it. I am not against common sense things to reduce radiation exposure. Though I am on record for saying that zero floraoscopy ablation business is an unnecessary parlor trick because there is essentially zero risk from doing one or two minutes of X-ray say during the transeptal. Keep in mind that many of these zero-floro-enthusias also do by VCRT devices where they bathe themselves in direct exposure to X-ray for 30 to 60 minutes. So a minute of flora during a transeptal is nothing in relative terms. Now also notable is that the laudable move to radial access for cardiac angiography has increased radiation exposure to the doctor versus femoral access, but it's a clear win for patients so we do it. Now the point of this discussion is to challenge your colleagues. causality thinking in the matter of muscular skeletal risks from a career in the cath lab. Medscape has had many stories on neck and back issues in the cath lab and I'll cite one of them. The social media also chronicles cases of orthopedic surgeries in cardiologists from working in the cath lab. Here is a statement from the document and it is taken as level A evidence as if the sky is blue and the following is true. The added weight of protective aprons typically 5 to 15 pounds, worn for prolonged periods is associated with cervical and lumbar spine disease as well as hip knee and ankle joint pathologies. And in the paper they even give you a reference, reference 21. This looks like a fact. But the reference goes to a 2014 survey of doctors, not on RCT, not on observational comparison study, a survey. Now the document also cites a 1997 paper in the American Journal of Cardiology that found that get this 45% of cardiologists self reported neck and back injuries versus 23% of orthopedic surgeons and 20% of rheumatologists. Now these sorts of studies have led to the belief that being a cardiologist who does procedures is hazardous to your orthopedic health and I don't believe it. I don't believe it one bit. And though I have had two level fusion in my neck, I challenge you all to look at the actual data and apply critical appraisal to it as an exercise in thinking. I have done some research this week and I went through PubMed and I used some LLMs and Google search engines and all I can find are tiny survey studies and one case control study from Mayo Clinic published in Jack in 2015. But this paper was really just a survey study and found an employee that were involved with procedures reported quote work related pain more often than a control group who does not do procedures. The numbers 54.7% versus 44.7%. As if that's any kind of data. This paper also noted that non-MD's like nurses had the highest reports of musculoskeletal pain. And a surgery also has a systematic review of studies, but the systematic review of studies included just more surveys. And so while there are individual reports of doctors so and so having neck and back problems amongst cardiologists like me for instance, there is literally zero empirical evidence that cardiologists are any more at risk than age match controls who are lawyers, engineers, accountants or firefighters or factory workers. Now we think cardiologists are more at risk because we observe single cases. Maybe there's this tall cardiologist who has been doing procedures for 30 years and had to have neck surgery. But this is how we are fooled. You cannot make causal claims from single cases. Take my case of neck fusion. I've raised bikes competitively for 30 years. Food and Mountain bikes was my cervical disease related to that or the cath lab. I've seen oodles of patients with a fib just like you have for pre-op clearance who are neither cyclists nor cardiologists and they were having pre-op clearance for neck and back disease. They weren't having any of these risk factors. How does the incidence of neck and back injuries in cardiologists compare to general public? I could find no study looking at that. Maybe if cardiologists are generally healthier due to our wealth is possible that being a cardiologist is actually protective. Now look, I have seen some cardiologists on Twitter accuse me of being an idiot about this and be just being contraignant for the sake of attention and both those things may be true. But my purpose in proposing this topic and challenging you has little to do with the danger of cardiology as a career and more an exercise systematic neutral-marshan empirical thinking. If this podcast is about anything it is about strong, not soft thinking. Now when you cite a colleague or yourself with neck injuries and then you make a causal leap you have no idea if it was from cardiology or other lifestyle factors or or the most common cause of most disease, bad luck. So yes, reduce radiation exposure. Yes, take measures to keep your back and neck healthy mostly through strength and flexibility exercises but please don't make causal leaps in the total absence of empirical evidence. So that's it for this week in cardiology. As always, I'm grateful that you listened. Thank you. And remember if you liked this podcast please take the time to give us a rating, write us a review, these things help others find us. And if you disagree with anything I've said please write me a note we can do listen or feedback. Until next week this is John Mandrola from the Heart.org Medscape Cardiology. Any views expressed are the presenters own and do not necessarily reflect the views of WebMD or Medscape.