Aug 01 2025 This Week in Cardiology

Medscape

3 days ago

Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast , download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only. In This Week's Podcast
For the week ending August 1, 2025, John Mandrola, MD, comments on the following topics: exercise and CV outcomes, aldosterone modulation, AI for ECG reading, GLP-1 comparisons, end-of-life decisions, and another well-meaning policy that caused harm in veterans.
My former partner, Anthony Pearson, an echocardiographer, super-smart person and blogger known as the Skeptical Cardiologist, wrote to me about my comments on exercise.
By email, he wrote:
I was shocked to hear you quote 'major guidelines' and 'numerous observational studies' to support the concept that physical activity lowers CV death, etc.
I was even more shocked to hear you discuss the 10,000-step study (again purely observational data) as if the higher step counts were reducing your CV death rate, etc.
Have you looked at the RCTs in this area?
Why do you have such intense blinders on when it comes to critical analysis of the data supporting exercise and physical activity?
You don't have to answer. I know why.
The logic is that exercise is good. It's good for me. People should exercise more. We can't possibly critique the epidemiologic data that establishes the CV health benefits because then people might exercise less.
At the very least you should throw in a limitation statement when quoting these types of studies.
Nonsedentarily Yours,
Anthony
I love this comment. Indeed, the empirical evidence for exercise is weak to nonexistent. It would be nearly impossible to study lifelong exercise and CV outcomes. Problem A is the timeline Problem B is the ethics of randomizing people to no-exercise. And Problem C is maintaining treatment adherence.
You can no more study exercise empirically than you can smoking cessation.
Yet I believe exercise is one of those interventions that does not require randomized data. And I also believe the epidemiologic data is utterly confounded. Not least because (a) people who exercise regularly likely do other things that promote health; (b) reverse causation is surely present (ie, people who are healthier likely exercise more than people who do not because of their good health); and (c) scant few people can be accurate in estimating their exercise amounts.
So, my answer to the skeptical cardiologist, who is worth following and reading, is that he is correct on the technicalities of the empirical evidence, which is terrible, but I am also correct to promote exercise in the same way we could promote clean air and being kind to others. You don't need data to think kindness is beneficial, and I don't need RCTs to believe in exercise. Aldosterone Modulation in Cardio-Kidney Disease
Journal of the American College of Cardiology has a state-of-the-art review on aldosterone modulation in cardio-kidney diseases. I mention it because it's a classic scenario, isn't it? Right after approval of a new expensive medication, you can bet there will be disease review articles.
FDA approved the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone on July 9. Now we have a major review article discussing the two conditions for which the drug will be used: chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF).
This will be brief because I don't want to be a broken record: It boggles my mind that finerenone was not studied against spironolactone. Finerenone beat placebo, mostly for nonfatal outcomes, but we don't know if it would have beat the $4 per month generic spironolactone. Later on in the podcast I will discuss a comparison drug study—which we need more of.
My points here are to highlight (a) the pattern of review articles following expensive drug approvals, and (b) I will be starting with spironolactone, and (c) MRAs are still the most underused drugs in all of cardiology. Look up the RALES trial of spironolactone vs placebo in HFrEF. It's one of the largest effect sizes in cardiac therapeutics — 9% absolute risk reduction in death; number needed to treat (NNT) to prevent death 11.
If I were czar of HF therapeutics, I would push for more MRA focus. I see it nearly every week. A patient comes in with HF, and they get sacubitril/valsartan, metoprolol XL, and dapagliflozin. Two of these three will crush the patient's budget.
Far better, for many patients with normal American drug coverage would be lisinopril at the highest dose possible, spironolactone, and carvedilol — given last and only when stable on ACE inhibitor and MRAs. Shoot for minimally disruptive care whenever possible.
The American Journal of Emergency Medicine has a neat study out this week comparing the accuracy of cath lab activation (CLA) for ST-elevation myocardial infarction (STEMI)-equivalent and STEMI-mimic ECGs.
I really like this study. And it's an important problem, as the identification of STEMI in the first minutes of a person's presentation is crucial.
The aim was to measure doctor accuracy vs the machine learning-based artificial intelligence (AI) algorithm from Queen of Hearts, which is a deep neural network model. You can use it on your phone. It determines the presence or absence of an occlusion myocardial infarction (OMI).
The PMcardio STEMI AI ECG model received FDA Breakthrough Device Designation in March 2025 but is yet to be cleared by FDA for marketing in the US.
Americans need to wait for FDA approval, but there's an opportunity to get early access to the PM Cardio AI bot through a beta signup. It is available on Android and Apple app stores in the European Union and UK.
Over 2500 hospitals are on the waiting list, and it's currently being tested in pilot programs at over 60 global centers.
For this study, done in San Antonio, in a hospital system that has two community hospitals and four stand-alone emergency departments (EDs), the authors chose 18 tough ECGs. I know this because they are in the Supplement. And I had to really study them. These included four STEMI-equivalent types which require immediate reperfusion therapy. They added an ECG with Wellens' T-waves and aVR STEMI. They also included transient STEMI and right bundle branch block (RBBB) with left anterior fascicular block (LAFB) OMI. Eight ECGs representing STEMI-mimics were included to test false-positive cath lab activation.
Again, my initial reaction to the study is that these could be highly selected ECGs, perhaps to accentuate doctor/AI differences. Maybe they were, but looking at them, these are real ECGs, and they are the type of ECGs that cause brain stress in reading them.
One important exclusion was ECGs seen in pericarditis, Takotsubo cardiomyopathy, and Prinzmetal angina since there are limited published criteria differentiating them from OMI.
In sum, there were 12 ECG types that warranted immediate angiography and 6 ECGs that were mimics that warranted no cath lab activation.
The ECGs were shown to 53 emergency medicine docs, 42 cardiologists, and the AI algorithm. The ref standard was angiography. Was there an OMI or not? Outcome was a binary outcome. CLA or not. Interpretation accuracies were similar between EM docs and cardiologists both were 66%.
But both were hugely lower than the AI model, which accurately called cath lab activation (CLA) in 89%.
Doctors most frequently misclassified the de Winter pattern, transient STEMI, hyperacute t-wave OMI, and bundle branch ECGs
The Queen of Hearts AI algorithm misclassified only two ECG types: left bundle branch block OMI (Sgarbossa (+) LBBB*) and left ventricular aneurysms. These same ECG types also challenged physicians, with only 14 % and 58 % of physicians correctly interpreting them, respectively.
Finally, EM docs missed 41 % of true OMIs (195/477) and overcalled 32 % of non-OMIs (133/415), whereas Queen of Hearts AI missed only 11 % and overcalled 11 %.
Overall physician accuracy was low (66 %), consistent with prior studies reporting 70% accuracy using fewer ambiguous ECGs.
There were nearly identical accuracies between EM doctors and cardiologists (65.6% and 65.5%, respectively; P = .969).
The ECG types most frequently misinterpreted include LBBB (±OMI), transient STEMI, and hyperacute T-waves as well as de Winter T-waves
The Queen of Hearts AI algorithm was more accurate than physicians (89% vs. 66%, P < .001), correctly classifying all ECGs except left ventricular (LV) aneurysm and LBBB with OMI, indicating potential to improve care and resource utilization.
I find this a remarkable study. The AI is clearly better. The ECGs were hard, but they are real, and I've seen them reviewed in peer review meetings as missed STEMI.
No one misses the 3-4 mm tombstones ST elevations. It's the subtle STEMI mimics that are tough. If you are a patient with an occluded left anterior descending (LAD) artery but not a conclusive ECG, you hope either for a) luck or b) a master ECG reader, or c) a really good AI algorithm.
Scientifically, I wonder if the best solution is smart doctors who have seen the patient and have Bayesian priors based on history and general appearance (MIs often look like MIs from the door) plus AI vs just AI. It's a false comparison because I don't think that study will ever be done, as it's hard for me to envision an emergency room without a doctor. (But I could not have imagined medicine with smartphones before smartphones).
Nonetheless, I have no idea why the FDA would not approve such a device for use. It looks like an important adjunct for getting to the proper diagnosis. I see it as similar to point-of-care ultrasound for central venous access. Sure. You get into a central vein without ultrasound, but why would you?
In the case of ECGs and CLA, sure, you can do it without AI, but why would you? The STEMI equivalents and mimics aren't rare and the Queen of Hearts looks quite good.
Technology is amazing.
Eli Lilly, the maker of tirzepatide, a GIP/GLP-1 dual agonist, announced results of the SURPASS-CVOT trial comparing tirzepatide (Mounjaro) to dulaglutide (Trulicity) in patients with diabetes and established cardiovascular disease (CVD).
The trial began in 2020, enrolled about 13,000 patients and the company reported the topline results this week.
Dulaglutide was shown to reduce cardiovascular outcomes in patients with type 2 diabetes (T2D) and established CVD or high risk for CVD in the REWIND trial, The Lancet 2019. The results were close on the primary endpoint of MI, stroke, CV death — 12% in dulaglutide group vs 13.4% in placebo. HR 0.88 (0.79-0.99) and P = .026.
In the SURPASS CVOT trial, Lilly says the risk of cardiovascular death, heart attack, or stroke was 8% lower for tirzepatide vs dulaglutide (hazard ratio: 0.92; 95.3% CI, 0.83-1.01), P = .086, meeting the prespecified criteria for non-inferiority.
Tirzepatide showed consistent results across all three components of the MACE-3 composite endpoint. The rate of all-cause mortality was 16% lower for tirzepatide vs dulaglutide (hazard ratio: 0.84; 95% CI, 0.75-0.94).
There were also positive results in secondary endpoints: slower slope of estimated glomerular filtration rate (eGFR) decline, more reduction of A1c, and -12% vs -5% body weight reduction with tirzepatide vs dulaglutide.
Key opinion leader Muthiah Vaduganathan wrote on Twitter that 'the game has changed' — SURPASS CVOT meets its primary and secondary endpoints in first head-to-head CV outcomes trial. He emphasized the 16% lower risk of all-cause mortality.
Yet, the always reasonable Sanjay Kaul on Twitter notes that SURPASS was powered for 15% RRR in MACE. And the PEP comes out only 8% lower with the 95% CI of 0.83-1.01 barely containing the HR 0.85.
Kaul also notes that the superiority of the comparator dulaglutide has not been established in this patient population. What? I told you the REWIND trial of dulaglutide vs placebo was positive. Yes, it was, but Kaul notes that the subgroup of patients with established atherosclerotic vascular disease (about a third of patients) the HR of dulaglutide vs placebo was 0.87 (0.74-1.02).
Kaul also asks what to make of the 16% reduction in all-cause mortality. It's a good question because you only have an 8% reduction in MACE, and Lilly tells us that tirzepatide reduced A1c, weight, and slowed CKD but no significant difference in CV events?
My two cents are that all-cause mortality is likely a noise issue. The P value was not adjusted for multiple testing, but more important is that if a drug is a cardiac disease modifier, then CV death and CV outcomes should drive the reduction in death. We need to see the full results.
Another issue is that tirzepatide was titrated to max dose and dulaglutide was fixed at one dose.
Furthermore, I have a real problem with a non-inferiority design here. Non-inferiority designs are to be used for interventions that offer something less invasive, less costly or less risky. None of that is true with tirzepatide.
In these early trial results, my take-home message is that tirzepatide failed to show superiority of dulaglutide. The HR was only 8% relative risk reduction and the CI went above 1, with P value well above .05.
We will wait for the trial results at the European Association of Diabetes.
Doctors' Own End-of-Life Choices Defy Common Medical Practice
BMJ Journal of Medical Ethics published a survey of physicians' preferences for their own end of life. The survey included doctors from Belgium, Italy, Canada, the United States, and Australia. More than 1100 responses were analyzed.
Physicians rarely considered life-sustaining practices a very good option (in cancer and Alzheimer's respectively: cardiopulmonary resuscitation, 0.5% and 0.2%; mechanical ventilation, 0.8% and 0.3%; tube feeding, 3.5% and 3.8%).
About half of physicians considered euthanasia a very good option (respectively, 54.2% and 51.5%).
Physicians practicing in a jurisdiction with a legal option for both euthanasia and physician-assisted suicide were more likely to consider euthanasia a very good option for both cancer (odds ratio 3.1) and Alzheimer's (odds ratio 1.9).
I cover this paper because I continue to be struck by the severity of illness in hospitalized patients. Nothing has changed from when I started 29 years ago. I used to remember coming home and telling my wife Staci how much we were torturing old people in ICUs. That was in the 1990s. Well, nothing has changed. I see consults nearly every day at our place and many of the people we are asked to see because of ventricular tachycardia (VT) or atrial fibrillation (AF) or bradycardia are weeks or months from dying—not of the arrhythmia, and not of one disease, but rather a multitude of diseases, resulting in severe frailty.
So you read this survey of docs, and you get the impression that since doctors know better, they would not be stuck in the loop of hospitalizations and ICU stays.
But whenever one of these surveys on doctors' preferences comes out, I go back to Dan Matlock's paper in 2016. It's titled, 'How U.S. Doctors Die: A Cohort Study of Healthcare Use at the End of Life.'
They found that when looking at actual Medicare data of US physicians, doctors spent the same number of days in the hospital and ICU in the last six months of life as did non-doctors. Doctors in this study spent a few more days in hospice than non-MD's but the take-home was that while doctors may express a desire not to have futile care at the end-of-life, in reality they suffer as much as non-doctors.
No idea I have had gets stronger than this one: the challenge of modern cardiologists is not having something to do for people, but whether we should do it . With every new advance, percutaneous valve procedures, pulsed field ablation (PFA) for AF ablation, and chronic total occlusion percutaneous coronary intervention (CTO PCI) procedures, the question of using these procedures in older sicker patients gets harder and harder.
We can do transcatheter aortic valve implantation and open valves, put in pacemakers and fix bradycardia; we can put in cardiac resynchronization therapy devices and reverse LBBB, and now with PFA, we can ablate about anything in the left atrium.
But in many of the inpatient consults I see, none of what we can do will fix the dying process of old age. It's super hard. I don't have an answer for all this suffering we inflict in the last months or years of life.
Take VT ablation, one of the sexiest new movements in EP. You see tons of it on Twitter. Gorgeous pictures of diastolic buffets of e-grams and colorful 3D maps. But I will tell you that, in reality, many of these patients have VT because of end-stage cardiomyopathy.
You want to, of course, have the skills to ablate VT because a minority of patients have an isolated scar that can be ablated, and that patient can then live years of good life. But gosh, many of these patients have VT because they've successfully survived an MI and heart failure 20 years ago. They've had a great run.
I don't mean to be preachy in this topic; in reality, I often don't know when to stop. But I do know that stopping is often the right choice. I would remind listeners that all of us have end dates, and the job of the modern physician is to help people have a good life and a good death. We are much better at the former than the latter.
I want to close today with another chapter on well-meaning policies that make great sense. It's one of the most dangerous concepts in healthcare.
A few years ago, there was an uproar about access to care in VA hospitals. Veterans often live far from a facility. There are substantial wait times.
So, Congress passed the MISSION act, which stands for Maintaining Internal Systems and Strengthening Integrated Outside Networks.
This allowed veterans who lived longer than an hour drive to get care outside the VA, closer to home, because that makes sense.
Well, JAMA has published a very interesting observational study of cardiac outcomes from the MISSION act.
The authors, led by a team in Philadelphia, did a retrospective difference in difference cohort study of veterans who had PCI, CABG or AVR between 2016 and 2022 in non-VA hospitals covered under the MISSION act or in VA hospitals.
The two outcomes were MACE (MI, stroke or hospitalization for CV cause or death within 30 days of the procedure) and travel time.
This was a huge database study looking at the three procedures. Tens of thousands of patients in each group. The two main groups were far and near patients.
The first finding was that after MISSION act implantation, for PCI, coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), there were much larger percentages of far rather than near patients who received these procedures in non-VA hospitals.
The second finding — and hint — is that far patients who received procedures at non-VA hospitals were more likely to receive care at nonteaching, smaller, rural, and for-profit hospitals than near patients receiving non-VA care.
The third finding was to look at outcomes before MISSION act: October 1, 2016, to June 5, 2019. The difference in travel times, probability of choosing VA, and 30-day MACE showed no statistically significant difference-in-differences between the 2 groups. That's important, because it provides support for the preintervention parallel trends assumption critical to the validity of difference-in-differences analyses.
After the MISSION act, implemented in 2019, travel times increased a tiny bit in near patients but decreased by a lot in far patients. I think travel time increased a bit in near patients because it was not just distance but also wait times could allow veterans to go to other hospitals and non-VA hospitals may be farther away than the VA.
Indeed PCI, CABG and AVR volume in VA hospitals decreased quite a bit after MISSION implementation.
Here is the key result:
Far patients undergoing PCI had a 2.3 percentage point adjusted mean increase in 30-day major adverse cardiovascular events (MACE) rates compared with a 0.5 percentage point adjusted mean decrease in MACE rates among near patients (difference in differences, 2.8 percentage points; P < .001).
Far patients undergoing CABG had a 1.6 percentage point adjusted mean increase in 30-day MACE rates compared with a 6.5 percentage point adjusted mean decrease among near patients (difference in differences, 8.1 percentage points; P < .001).
Both near and far patients undergoing AVR had similar adjusted mean increases (2.2 percentage points vs 3.4 percentage points; P = .45) in 30-day MACE.
The authors concluded that:
'MISSION Act implementation was associated with substantial decreases in travel times among veterans who became geographically eligible for non-VA care. For these patients undergoing PCI or CABG, MISSION Act implementation was also associated with worsened 30-day MACE rates.'
I remember thinking this was going to be the likely result. Yes, it's nice to get care closer to home. I often see rich endurance athletes who travel to see me. If they should have a procedure, I tell them to get it close to home. Because AF ablation is a well-practiced procedure that can be done in all major cities.
But PCI, CABG, and AVR are procedures that not only require a skilled doctor but also a skilled team and a system. And while VA hospitals may not have great food or great decorations, they often have great processes and dedicated staff. In fact, in the introduction of this paper, the authors cite three observational studies finding that VA cath labs have better mortality rates than non-VA cath labs. I don't find this a surprising finding at all.
So, the MISSION act focuses on improving access to care. And it does. Veterans have shorter drive times to get care. But increasing care outside the VA results in worse results — at least for PCI and CABG.
I should add that this is observational and there may be confounding. While baseline characteristics in the two groups were similar, those who live farther from the VA may be sicker. I doubt this because if there is one thing US hospitals are good at, it is making patients look sicker on paper.
So I find these results highly likely. Care in the US has lots of variability. VA care is standardized. I see a similarity to say Canadian healthcare. When I visit Canada, I am struck by how cardiac procedures are done in small numbers of hospitals. This means Canadians having procedures have doctors and teams who do a lot of the procedure. They may have to travel and wait, but when they have the procedure, it is done by experts. In the periphery of major cities in the US, it's the Wild West. For instance, in Louisville, there are about 8 or 9 centers doing AF ablation. You may get a skilled doctor in the US who has tons of experience, but you may not.
This paper suggests the policy of allowing veterans to seek faster and closer care resulted in worse outcomes.
The lessons are both specific and general. Specifically, it was a bad idea to think that in the US, more convenient healthcare was a positive.
And generally, it would have been far better to implement this policy in RCT pilot form first. Then, instead of looking back and seeing the harm it caused, policymakers could have adjusted midstream and mitigated harm.
I don't why we feel that trials are needed for new drugs and devices but not policies. In fact, policies may affect more people than drugs and procedures, and I think it's even more important to study these in RCT form.