Sep 11 2026 This Week in Cardiology

0:00You'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 September 11th, 2026. This week I'll have my second ESC recap and I'll do two breaking stories in last week,

1:00one on lipoprotein.a and another on a novel AI ECG app. So first is lipoprotein.a disappointment. In a press release, Novartis announced that their phase three cardiovascular outcomes trial of the lipoprotein.a lowering drug pellacarsin did not meet its primary endpoint. The drug is an anti-sense oligoneucleotide which actually succeeded in lowering lipoprotein little A levels, but these reductions did not lead to reductions in the events in the 8,000 patient trial that was carried on for approximately three years. This is the horizon trial and it enrolled patients that had to have a lipoprotein little A greater than 70 milligrams per deciliter, a previous MI or stroke or clinically significant PAD. The trial was a event driven and powered to find a 20% reduction in the composite mace

2:03endpoint that included MI strokes, CV death and re-vascularization. They also looked at a subpopulation of patients with lipoprotein little A levels greater than 90. Now, this is a really big deal. I mean, recent guidelines have recommended measuring the genetically determined lipoprotein little A level, mostly because it is clearly associated with higher rates of cardiovascular events. What's more, Mendelian randomization studies, often called natures RCTs, have suggested a high likelihood of causality in cardiac events. But the negative outcomes trial, and it's a huge trial at that 8,000 patient, and it starts to question the notion that lipoprotein little A is causal and may in fact be simply a marker of increased CV risk. Now we should also remember that Niasin can reduce lipoprotein little A's by a little bit, 20 to 30%, but also has shown a lack of cardiovascular outcomes benefit on backgrounds

3:06high intensity statin therapy. So the idea that lipoprotein little A may be a non-causal marker makes sense. Not only that, there are now three other examples of non-causal biomarkers. We have HDL cholesterol, homocysteine, and several inflammatory markers, most recently, the failure of the IL-6 reducer, Zivol-Khemab bolster the suggestion that there are many risk markers that are not necessarily causal in atherosclerotic events. Now I'm not a lipidologist, but it may be that since lipoprotein little A is an APOB particle, and if there are so few APOB particles from intensive lipid lowering therapy, the incremental, incremental value of lowering lipoprotein little A is going to be smaller. The translation may be lipoprotein little A has a small causal effect, but the fact that patients in Horizon Trial were so maximally medically managed that the incremental benefit

4:11over high intensity background therapy is too small to detect. Proponents of lipoprotein little A lowering might also say that three years is not enough to treat a lifetime exposure, because remember that lipoprotein little A is genetically determined. I would counter that, well that may be true, but three years was enough for statins and PCSK-9 drugs to show reductions in cardiovascular outcomes. I should also note that there are numerous other trials of lipoprotein little A reducing drugs ongoing, so Horizon is sort of a first chapter. Lily, Amgen, and Silas, therapeutics all have candidates in the market to develop drugs for lipoprotein little A reduction. So the final translation of this story is A, biology is hard. B, plausibility and phase two trials are never enough to help people in cardiology, the drug or surgery must reduce hard outcomes, not a marker like LDL or HDL or lipoprotein little

5:15A. All right, second breaking story is that the FDA clears an AI ECG app for acute MI detection, and I say thank goodness. I've spoken previously on this podcast about studies showing that the Queen of Hearts AI algorithm beats doctors when it comes to picking up occlusion MIs from an ECG. And this is obviously the critical step, right? A patient comes to the emergency room or is picked up in an ambulance and the first thing that we use to restratify is the ECG and we have to be able to read it. Well this week FDA granted something called the NOVO authorization to this device. And it had a breakthrough device designation which was granted in March of 2025. And basically the algorithm is you take a picture of the ECG and you put it into the app and it tells you whether it's an occlusion MI. One of the more recent studies on the AI ECG was published in Jack Interventions in October 25th. This retrospective review of about a thousand suspected chemists that triggered emergent

6:19catholic activation, basically the app really beats standard triage techniques. I also loved the shrewyer at all paper where they had 18 ECGs shown to ER docs, cardiologist and the app and the app bested them all. And the best part of that paper which I'll link to and it's in the American Journal of Immurgency Medicine is that they actually have the ECGs and you can kind of test yourself. Now I've used the app in beta form and it is incredibly good. The main help I see with it is what is called stemmy mimics and that is the case where it isn't classic ST elevation like you would see in a typical stemmy. There's hyperacute T waves or there's subtle ST elevation and you really only can notice it because you have to look at the ST depression in the reciprocal leads to look at the ST segments in the infarcted lead. I'm super positive on this story and app because in my two decades of sitting on our hospital

7:23peer review committee the number one cause of misstemmies is poor ECG reading and I say good on the makers of this app. This is a advance and I highly recommend you download the app and start using it. I think it will make you a better ECG reader. All right first ESC recap story and I guess the story today is the story of negative trials. I'm going to talk about the target CTCA trial. Professor Nicholas Mills from Edinburgh presented results of the target CTCA trial at ESC and this was a multi-center RCT of patients who presented to an ER in 14 hospitals in the UK. They had had MI ruled out but they did have high sensitivity proponents indicating an intermediate risk of a cardiovascular event. The randomization was to receive a CTCA or receive standard care in the primary outcome was a good one MI or CV death. In about 4400 patients were assessed for eligibility and 3100 patients

8:27mean age 61 were randomized one to one. Right off the bat that's a pretty good ratio as a high percentage of people screened were enrolled. The entry criteria required patients to have cardiac proponents between the low risk threshold of less than 5 nanograms per liter and the sex-specific 99th percentile of the upper limits of normal and we see these patients all the time. The main result after a medium of three years a primary outcome had occurred in 112 participants that 7.1 percent in the CT group and in 7.3 percent in the standard care group that adjusted hazard ratio 0.95 conference intervals from 0.73 to 1.23 and obviously a non-significant p-value of 0.7 and the cap limire curves were superimposed. I mean they were nearly identical. There was no obvious subgroup signals except that CTCA appeared to benefit

9:28patients at the lowest risk by heart score but I think this is likely noise given the low number of events 22 and 39 respectively. So my comments here we go with guidelines being wrong again. US guidelines recommend a CTCA in patients with chest pain were considered intermediate risk in order to rule out obstructive disease and US guidelines give a 1A recommendation like you should do this. ESC guidelines give it a 2A recommendations but the studies underpinning these recommendations were done before high sensitivity troponin assays were available. Now from this trial we learned that CTCA had no benefit and not only that the trial was conducted in the UK which I would argue is a best case scenario for CT imaging because there is little incentive in the national health care system to do downstream testing and inappropriate coronary revascularization.

10:30Notable was that the actual standard care testing was so low right? Non trial CT coronary angiography 6.5% invasive coronary angiography 8.7% non invasive stress imaging 9.7% which means to me that you cannot say target CTCA failed because so many in the standard arm got imaging. It looks to me like most of the control arm got very little imaging. As I have said many times before in the US coronary CT imaging machines are akin to cash machines because in this country if they pick up any disease in a patient with chest pain and non normal high sensitivity troponins that patient is going to get a hotline to the cath lab and if there is a lesion it's unlikely to be left untreated an incidental coronary disease treated with PCI and then lifelong anti-platelet therapy because of the stint rather than simply using guideline directed medical therapy with statins and lifestyle

11:32management that's likely to cause a net harm. So imaging in the US surely helps hospitals and doctors but not patients but even in the UK where such a cascade is less likely adding a CTCA did nothing over standard care. Now what I want you all to consider is how this trial is stone cold negative versus the hugely positive Scott Hart trial which added CTA to standard stress imaging. Now the setting was a little different in that Scott Hart enrolled stable outpatients with chest pain but to this day I find it hard to explain how in Scott Hart a CTCA reduced mace outcomes by 41% and 1.6% absolute risk reduction versus a stress imaging pathway just doing the CT scan reduced cardiovascular outcomes. Now the thesis was that the diagnosis of anatomic disease led to more statin use but when you look at Scott Hart the delta in statin use was really small and if

12:35it was due to stans you'd have to posit an NNT of about three for the stans which is hugely higher than what we know statins do. So if you can explain why Scott Hart showed that CTCA was an event reducer but CTCA in a higher risk group of patients in this trial did nothing I'm all ears. In general though I believe the anatomic diagnosis of CAD is overrated first temporarily over time the rate of MI we know is declining in the population. Trans fats have been removed smoking is down and so the baseline incidence of cardiovascular events is lower. Second most of these patients who are Scott Hart like or target CTCA like are eligible for lipid lowering therapy and lifestyle intervention and it's hard to improve over that. And third modern revascularization is pretty amazing so yes it's better to prevent an event

13:35but when an event occurs an ACS event modern acute PCI is shockingly good at preventing bad outcomes. For instance I hardly see post MI patients eligible for ICDs largely because acute stemming here is so amazing in preserving myocardium and basic tenant of cardiovascular screening or any screening is that the better acute therapy becomes the less value there is in early detection with screening and it's the same in heart disease as it is with cancer. Now make no mistake I'm not saying we should ignore symptoms or hugely high risk patients rather I'm saying we ought to be a lot humbler about the value of putting people into x-ray machines who do not have evidence of obvious ACS. Back out therapy with lifestyle interventions and statins is really good. Do look at the target CTA trial which studied a best case scenario for imaging and found zero evidence of benefit. All right next topic speaking of no benefit of imaging let's now talk about the core

14:41cow trial. I picked the core cow cardiovascular outcomes trial using the PCE pull cohort equation or CAQ to select statin therapy for primary prevention as one of my trials to look at and at ESESC in one of the hotlines Dr. Joseph Mollstein from University of Utah presented it at ESESC. It's being considered for publication in CHAC but it's not yet out. It was about 5,500 patients were randomized after sending letters to more than 75,000 people from the medical record so it was done in Utah. These were all primary prevention patients who were not yet on stands. Now the first interesting finding was that stands were recommended or considered for 73% of the patients in the PCE arm full core equation arm versus only 22% in the CAC arm. Pause there that's a huge difference. Now core cow is a pragmatic trial so the number of patients who actually had

15:43a statin prescription was only 18% in the PCE arm and 13.6% in the CAC arm. Again just to say it one more time in the PCE arm 73% were considered based on the equation and 18% took the statin. In the CAC arm only 22% were recommended and 13.6% ended up taking stands. The actual effect on LDL was that it was reduced in both arms but only 14% in the PCE arm versus 27% in the CAC arm. This trial was long about six years and the mace endpoint was 2.7% in each arm. There was no difference in the Camp Le Meyer curves that hazard ratio is 0.99 but but the upper bound of the 95% conference interval was greater than the predetermined non-inferiority margin of 1.3 so technically even though event rates were identical the trial did not meet

16:45non-inferiority. Dr. Molstein concluded that compared with the PCE guided strategy the CAC guided strategy led to recommending statins in a third fewer patients but ended up with better statin adherence in more LDL cholesterol reduction but such a strategy did not lead to non-inferiority when it came to mace outcomes. Like I said the trials on the reviewer jacket will read the full paper and will be interested in the full paper but we can make some comments now. First I want to compliment the team in Utah for finally studying use of CAC as it is proposed. Proponents of CAC have made the case through observational studies and expert opinion that the scan can help delineate statin decisions and intermediate risk patients. They say that visualization of actual disease is powerful and that CAC zero which has reached meme status may allow no treatment in lower risk patients even though I would argue that no calcium in the coronaries does

17:47not mean no disease. Yet core cow is really I think the first attempt to actually randomize patients into an outcomes trial with this strategy. Sadly the DSMB recommended stopping the outcomes trial early due to low events and the rise of the prevent score over the PCE score which again the prevent score is based on expert opinion and not trials. Yet the data we have is that CAC guided decision making was not non-inferior to pulled cohort equation. Why this is the case is not as important as the fact that the upper bound of the mace outcomes interval was more than 30% higher than using simple clinical features. It could be that less statin use was the problem it could be downstream testing and non beneficial PCI led to CAC's failure to make non-inferiority but in the end results are results. Why is not is important as the results and results are the ones that matter. Now some may say that the events were similar 2.7 versus 2.7 so the CAC guided strategy is fine.

18:55I would disagree strongly. First the strategy failed to be less than 30% worse for events so it doesn't make non-inferiority. Second I did not feel non-inferiority was even an appropriate test right because CAC involves radiation it involves imaging that puts the patient at risk for incidental findings and inappropriate re-vascularization of stable coroner disease. I think this should have been studied with superiority and if it was studied with superiority it would have clearly failed to be superior. This trial core-cal strengthens my belief that the test does not benefit patients and I feel better about never having ordered a coronary calcium scan. What I wish is that we had more trials like core-cal before an imaging test becomes established. I look forward to the publication but I doubt that my practice of not imaging people unless there is a chance that will improve health will change. My friends be afraid of imaging tests of all sorts.

19:58All right next topic is more on surrogate endpoints the Amuncin trial. Now this was on PCSK9 drugs and we know that PCSK9 drugs are very good at lowering LDL cholesterol and we know that lowering LDL cholesterol is especially important after a MI. We also know that statin drugs are super strong at reducing outcomes and provide a strong comparator group. The question for the Amuncin trial investigators is whether the in-cath lab evalocumab started before an urgent PCI whether that would improve clinical outcomes over basic care. This trial was conducted in 48 sites in six countries more than 2100 patients with stemmier non stemmi were randomized to evalocumab versus standard care. The primary endpoint was LDL cholesterol less than 55 and the main clinical endpoint was all caused death or unplanned hospitalization at 12 months. Now the first result is expected right 82

21:03percent of patients in the evalocumab achieved the LDL cholesterol less than 55 versus only 40% in the standard care arm. That odds ratio was 5.5. At six weeks the median LDL cholesterol was 16 milligrams per desolate or with evalocumab versus 56 was standard care alone. The main clinical endpoint however was not statistically lower. 14.6 versus 15.4% adjusted odds ratio 0.94 and clearly not statistically significant. So my comments. I see this as another example of surrogate measures not equating to outcomes. Yes the drug evalocumab shreds LDL cholesterol but here it had no effect on outcomes compared to standard care and I would not be distracted by the fact that the authors call LDL cholesterol lowering a primary endpoint. The proper endpoint, the only endpoint is outcomes and at one year the primary clinical outcome was not different.

22:09Nor was MI, CV, death, stroke or unplanned revascularization. Now you could say as the editorial is due that LDL cholesterol lowering is a marathon not a sprint and of course we know that Lippard lowering benefit is cumulative over time. The question though was whether extreme Lippard lowering early made a short-term difference in the highest risk post ACS patients and it did not. Now I wonder why exactly some thought it would make a difference over the short term over already intense therapy with statins and azidimib and other Lippard lowering drugs. And I am sorry to say this but I can't help wondering whether this was a hopeful marketing exercise. Now the trial was conducted by an action research organization in Paris and the trial was funded by an unrestricted grant from Amjand. The authors thank two doctors from Amjand in the credits at the end of the study. Let's talk about the trick IHF trial. This is tricuspid repair

23:13and it was an outcomes trial looking at percutaneous tricuspid repair. So at ESD we also had results from the trick IHF trial and I'm not even sure how to say this trial acronym it's TRIC-I-HF. The LINGLINGERAL published a manuscript. 360 patients was symptomatic severe TR and an increased risk of heart failure events were randomized in a 2-to-1 fashion to percutaneous type tricuspid repair versus medical therapy. And high risk for heart failure was defined by either a history of decomposition in the previous year or a presence of cardio-renal or cardio-hepatic syndrome. Now the strategy for tricuspid valve repair was selected by a heart team and any CE marked devices could be used basically though it was 66% Pascal system and 33% tri-clip system. The three-year trial had a primary endpoint of all-cause death, heart failure hospitalizations

24:15and quality of life improvement at one year. And if the between-group difference was significant that a second primary endpoint would be tested, a composite of death from any cause or hospitalization for heart failure through three years. The trial was conducted in experienced heart centers in Germany which ends up being important. Now come back to that the mean age of patients was 80 years. These were old patients and 56% were female. So the results. This was a hierarchical win-racial analysis and the win ratio for the first primary endpoint was 2.4 highly favorable for the tricuspid valve repair. The components of the endpoint with intervention first at one year so death was 13.1 versus 16.3 so lower in tricuspid repair, freedom for heart failure, 19.4 versus 44 so a huge win from freedom from heart failure and the Delta and KCCQ was 11.2 points positive for tricuspid repair

25:18and 4.3 for medical therapy. The capulomir estimate for freedom from death from any cause or hospitalization for a heart failure which was the second primary endpoint was 52% in the tricuspid repair group and 21.0% in the control arm and that's a hazard ratio of 0.40 so a 60% reduction in net secondary endpoint or the second primary endpoint. TR was also reduced as was functional class in the intervention there were major adverse events within 30 days and this was 14 patients or 6% in the tricuspid repair group so my comments while I believe that TR can be terrible and I have actually referred patients to the structural team for consideration of intervention I have severe problems with this trials design and you should too. You will not convince me a benefit of this procedure without a shame procedure. Now we know the previous tri-clip trials try to illuminate for instance were driven

26:23solely by quality of life issues and had no significant differences in heart failure or death in the primary analysis and if you're going to have a quality of life component in the outcome you need a proper placebo because an intervention versus tablet comparison is fatally flawed intervention puts out a much larger placebo signal period end of story. Now the enthusiast for tricuspid valve intervention will say okay but in this trial heart failure hospitalizations were substantially lower as well as KCCQ and my response is that the trial is unblinded and it's problematic patients randomized to the device have faith healing and those randomized to the control arm have subtraction anxiety meaning that you feel better when you feel fixed and if you're randomized to a trial and you have a severe valvular condition and you don't get the intervention you're likely or more likely to have symptoms of congestive heart failure and present to the emergency room

27:24but it isn't just the patients right the doctors too were not blinded and the decision to admit a patient for IV diuretics is a gray area subject to human nature. Now the trial is necessarily conducted at expert centers and experts tend to be enthusiast and it's a normal human nature to see a patient with a demon who has a device as less sick and capable of oral diuretics at home while if you see a device subtracted patient it's going to look sicker and you'll say to yourself this patient needs to come in for IV diuretics that's not nefarious it's human nature so heart failure hospitalization is a seriously susceptible endpoint in unblinded trials so no I am not likening this to a co-app like movement and I call on my structural heart colleagues to be brave and randomized to a proper placebo control so at least the patients can be blinded without that I remain skeptical that

28:24percutaneous repair of the tricuspid valve is a disease modifying procedure and worse enthusiasm about these results should not lead to a watchman-like expansion of this procedure it just shouldn't I think there may be a role for this procedure but we need proper studies with a proper sham control and so that's it for this week in cardiology next week I'll have more ESC review and probably the week after that there are so many trials from ESC to discuss until next week this is John Mandrola from the heart org medscape cardiology 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 presenters own and do not necessarily reflect the views of web MD or medscape