Oct 30 2026 This Week in Cardiology

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, Apple Podcasts, Spotify, or your preferred podcast provider.This podcast is intended only for healthcare professionals.Short Feedback Thanks to the Norwegian Cardiac Society for a wonderful time at the National Meeting in Oslo. I spoke on the five worst trials in cardiology that are used nonetheless, similar to my BCIS talk in the Spring but adding two. If I am reincarnated, I want to come back as a Scandinavian. I absolutely loved the food, weather, and love of endurance sport. Thanks to Eivind Westrum Aabel and Peder Myhre, who took me on a 5-mile trail run, then a sauna, then jumped into the 40° North Sea. What a shocker. I loved meeting so many Norwegian cardiologists, and thanks all for listening. And, oh, do I love the amazing fish and reindeer. Norway I think is now tied with Denmark as my favorite country to visit! I received a critique that this podcast is too heavy in EP. To this I say, a) I am an EP, so surely I am most interested and knowledgeable about arrhythmia, and b) I actually think arrhythmia matters are quite relevant clinically, as atrial fibrillation (AF) is one of the most common cardiac ailments. That said, I will be mindful that This Week in Cardiology is a general podcast. This weekend, for instance, is the big Transcatheter Cardiovascular Therapeutics (TCT 2026) meeting. So next week will be an interventional-heavy show.Syncope NEJM published the ASPIRED RCT, a UK pragmatic trial done at 45 hospitals. More than 2200 adults who had unexplained syncope after an initial emergency department (ED) assessment were randomized to a 14-day ECG patch or to site-level standard of care. Before we go into the trial, it’s pretty obvious that syncope is a hugely important condition to study. While it’s quasi-connected to EP, it’s really a general medicine and ED problem as much as a cardiac complaint. The authors tells us that there are about 1.2 million ED visits yearly in the US for syncope. About half the patients who have syncope have no obvious initial diagnosis. And there is an obvious reason for this: almost no one has syncope with a heart monitor on them. We have to take a history of the syncope and then work backwards, based on clinical judgment and really hard thinking on what likely happened. A Mandrola approach to syncope is likely similar to yours: After you sit down and listen to the exact story — and I mean everything — you put this person in one of two boxes: “I am worried” and “I am not too worried.” Otherwise known as, you risk-stratify these patients into a malignant or worrisome cause or a benign cause. A post-transcatheter aortic valve replacement patient with new left bundle branch block (LBBB) who passes out stone cold is in the “I AM WORRIED” box. A 25-year-old who gets hot and sweaty in a hot operating room and faints is in the “I AM NOT TOO WORRIED” box. The thing is that syncope is not often as clear cut as the two cases I just presented. So it has become common to send people out of the ED or hospital with a 14-day ECG patch, which allows detection of arrhythmia that may not have been seen when monitored in the ED. But even this does not cinch the diagnosis of syncope because oodles of people can have nocturnal pauses of 6 seconds from sleep apnea, and this is not the cause of their syncopal event.Trial Procedures and Patients The primary outcome was patient-reported syncope episodes after 1 year. The trialists screened more than 6000 patients to enroll the 2200. Mean age was 58 years but there was a big spread. Nearly half had suffered a previous syncopal episode. Cardiac disease at baseline was relatively uncommon. Coronary disease in 8%, previous MI in 6%, heart failure in 2%. Hypertension was present in about one third of patients.About 40% had a prodrome. Slightly more than a third of patients were admitted. The main index stay for syncope was about 3.5 days. Follow-up was by automated text or email, or phone calls every 4 weeks for 2 years. Results Slightly more patients were excluded from the primary analysis in the standard care arm — 13.1% vs 10.5%.However, importantly, slightly more patients in the standard arm had heart failure (HF), chronic kidney disease (CKD), chronic lung disease, and prior myocardial infarction (MI). Episodes of recurrent syncope were 1.37 ±5.10 with the patch vs 1.58 ±8.56 with standard care (incident rate ratio (IRR) 0.89; 95% CI, 0.68–1.18). Every other syncope measure was also null:Recurrence: 27.9% vs 28.6%.Episodes in the medical record: IRR, 0.90.Note that the rate of recurrence was well below the 40% the investigators assumed.Process outcomes went in the expected direction:Clinically significant arrhythmia: 22.0% vs 9.0% (odds ratio, 2.95), found sooner (median 22 vs 54.5 days).These were defined as nonsustained ventricular tachycardia (NSVT) (> 120 bpm for > 4 beats; pause > 6 secs; sinus bradycardia 30 seconds), sustained VT, Mobitz II or complete heart block.In the supplement, the largest difference was in NSVT (13 vs 104 patients) and sustained VT (6 vs 14) in the patch arm. There was actually more heart block in the standard-of-care arm (8 vs 4).Downstream treatment was more common in the intervention armPacemakers: 6.8% vs 4.6%.Antiarrhythmic drug starts: 10.8% vs 7.3%.ICDs: 0.6% vs 0.4%.Overall mortality, which was a secondary endpoint, favored the patch. Deaths were 1.5% vs 2.9% (OR, 0.50; 95% CI, 0.27–0.93). My Comments The Edinburgh authors were righty measured in their conclusions, that the monitors did not reduce the number of patient reported recurrent syncopal episodes. They do note the larger number of arrhythmias diagnosed and more downstream treatment in the ECG patch arm, and they cautiously hint at the possibility that the 50% reduction in death may have been due to pacing for malignant bradycardia. The mortality signal is interesting. It was 16 vs 31 patients who died in follow-up. The confidence intervals went from 0.27–0.93. This could be due to the interventions saving people, but with only 47 deaths, it could also be statistical noise or the fact that patients were slightly sicker in the standard care arm. When I first looked at the trial’s results, I was highly critical of the endpoint choice. I felt recurrent syncope, especially patient-reported, is a poor endpoint as it is infrequent, and much less important than picking up a malignant arrhythmia (which was far more common in the ECG patch arm). But after sleeping on it a bit, I have softened my view a bit. That the ECG patch picks up more arrhythmia is almost tautological, as that is what it does. But picking up arrhythmia, especially 5 beat NSVT runs or sinus bradycardia, is surely a surrogate outcome that is unlikely to be important. Similarly, the higher number of pacers, implantable cardioverter-defibrillators (ICDs), and antiarrhythmic drugs (AAD) in the treatment arm are also just surrogate endpoints. Just because you get a pacer or an ICD, that does not imply benefit to the patient. So I am less critical of the endpoint choice. The main problem though, as it is so many trials, is power. The authors estimated 40% recurrent syncope, and that the ECG patch would reduce it by 10%. These are very optimistic estimates. But the actual recurrences were lower. And the incidence rate ratio on the primary outcome was 0.89 (95% CI, 0.68–1.18). This roughly means that the patch could have reduced recurrent syncope by 32% or increased it by 18%. Sadly, this is a largely uninformative confidence interval. What’s more, about 10% of patients did not have follow-up. So, in the end, I would say that this “null” trial for the ECG patch does not provide enough evidence for us to not use the device in syncope. I would also not make the argument that the fact that it picked up more arrhythmia should be used as evidence of its benefit. That’s not correct, I don’t think. And finally, I am intrigued by the mortality signal. Yes, it could be noise, but gosh, it seems hazardous to ignore such an important endpoint as alive or dead. Fortunately, the authors tell us that a Canadian trial called REMOSYNCED is ongoing. Interestingly, this trial will have as its primary endpoint: Number of participants with arrhythmia that required treatment. Two Coronary Artery Calcium Studies The first one is risk of high coronary artery calcium (CAC) in young adults and it’s titled, “Advanced Subclinical Atherosclerosis in Young Individuals and Risk of Mortality Over 30 Years.” And this comes from the Coronary Artery Calcium Consortium.JAMA Cardiology has published a cohort study of nearly 13,000 adults with CAC above the 90th percentile. The goal was to correlate the long-term risk of all-cause, CV, and coronary mortality with high CAC.The study used the CAC consortium dataset, which includes referred adults with “clinically indicated” CAC scans. Four institutions from the US provided the data for the consortium.The study uses multivariable regression; in other words, they did correlations. Mean follow-up was 20 years. The specific group studied were young adults from age 30-45 with high CAC, as denoted by CAC ≥ 90th percentile. The comparator groups were those with CAC 0. The mean age was 40 years, 77% male. The distribution of CAC was as follows: 72% had CAC 013% had CAC 75-90%13% had CAC > 90%These are the comparator groups. Let me tell you how it is reported in the abstract and then I will tell you a better way to label the data.In the paper, the authors tell us that when you compare CAC >90% to CAC 0, there is an adjusted higher rate of all-cause, cardiovascular death, and coronary death. The hazard ratios (HR) are 1.87 for all-cause death, 2.6 for CV death, and 3.7 for coronary death. The HRs are also higher for CAC 75-90% vs CAC 0 but not as bad: 1.16 for all-cause death, 1.6 for CV death, and 2.0 for coronary death. And this: Over 30 years, the group with a CAC score greater than 90% had significantly higher modeled risk of all-cause death (12.9% vs 7.5%), CV death (4.5% vs 1.5%), and coronary death (3.0% vs 0.6%) mortality, compared with the group with a CAC score of 0.The authors concluded that:young adults with a CAC score greater than 90% face significantly higher long-term risk of all-cause, CV death, and coronary death, suggesting potential implications for guiding the intensification of preventive intervention in this high-risk phenotype. Their discussion makes CAC scans seem like penicillin in the 1930s. High CAC patients carried a large share of deaths, the guidelines miss this group, CAC >90% is a distinct phenotype, and early treatment pays off — citing here the JUPITER trial. They also write that CAC 0 is reassuring because the 1.5% 30-year mortality is low.This is the classic maximizer take. Akin to Thomas Sowell’s unconstrained vision. I have a different approach — consider it more like Sowell’s constrained vision. I see absolute risk differences from the perspective of a 40-year-adult seeking out my opinion. First of all, I would lean more on 10-20 year numbers because these are observed not modeled. I would also lean on CV death, because all-cause death is likely going to be most affected by the fact that adults with high CAC score likely have more other diseases. The absolute risks of CV death at 10 years is 0.9 vs 0.2% and at 20 years is 2.1 vs 0.7% for CAC > 90 vs CAC 0. Translated, that means about 98 of 100 people with high CAC do not die of cardiovascular disease, vs about 99 of 100 with 0 CAC.Another aspect that makes me less impressed by this analysis is the net or incremental benefit of CAC > 90% over the pooled cohort equation or PREVENT score. This isn’t given in this paper. The authors “adjust” for age, sex, hypertension, lipids, smoking, diabetes, and a family history of coronary heart disease, but they do no reclassification analysis of C-statistics. All adjustments in this paper were binary with no LDL level or blood pressure values used. Plus some of the data is self-reported. The high CAC arm also has more risk factors and surely would also have higher risk. They would likely be statin-eligible, so I don’t see the incremental value. Notice that I have yet to even mention that having a CAC scan is not free. This paper just correlates the high CAC with a higher relative risk, but without randomizing this in the real world, we have no idea what the value is. For instance, when a 40-year-old gets a scan like this in my city, they have a high chance of getting a coronary angiogram. And we know that getting a stent does not improve outcomes. We know there is risk from coronary angiography. I realize that is not how this test is supposed to be used. But it is how it is used in many zip codes in the US.I will say it again — all of the effort and money it takes to publish these observational analyses should be used, in my opinion, to do a big, randomized trial. More CAC DATA Speaking of incremental value and reclassification using CAC, let me tell you about another CAC paper that came out.The title of the paper, published 2 months ago, is “Predictive Utility of Coronary Artery Calcium Score Added to the PREVENT Atherosclerotic Cardiovascular Disease Equations.”JAMA published the observational cohort study using the MESA database. MESA is a community-based cohort recruited at six US field centers (Baltimore, Chicago, Los Angeles, New York, St Paul, Winston-Salem). The goal was to determine the change in predictive utility when adding CAC to the PREVENT equations. The MESA study includes baseline exams and longitudinal follow-up. For this August study, about 6000 adults aged 45-79 without heart disease were included. The exposure was 10-year atherosclerotic cardiovascular disease (ASCVD) risk from the PREVENT equation compared with the same equations plus CAC. The main outcomes were fatal and nonfatal MI or stroke in 10 years. Performance was assessed using the C-statistic, calibration slope, and reclassification index. Results 366 or 6% had an ASCVD event.For discrimination: The C-statistic rose from 0.73 to 0.75 with CAC, a change of 0.02 (95% CI, 0.01–0.03).For calibration: Both models were adequately calibrated. The slope was 1.09 for PREVENT alone and 0.92 with CAC.For net reclassification index (NRI): 0.095 (95% CI, 0.053–0.137), which is slightly positive. Here is a translation: In the whole cohort, about 18% of the cohort was reclassified in the “right” direction and about 4% in the “wrong” direction. So if you were reclassified by CAC over PREVENT, there was a 4 in 5 chance it was correct and 1 in 5 chance it was incorrect. Event rates in those with borderline PREVENT risk were: 1.9% with CAC = 0; 3.9% with CAC 1–99; 7.4% with CAC 100–299; and 14.3% with CAC ≥ 300.The authors concluded that: The addition of CAC score to the PREVENT-ASCVD equations across all risk groups overall only modestly improved and, in some groups, did not change model discrimination and reclassification. Reclassification results support selective use of CAC in those with borderline to intermediate risk estimated by the PREVENT-ASCVD equations. My take is different.My Comments A) There is essentially no difference in the C-statistic, 0.73 without CAC is not different from 0.75 with CAC. Technically, the C-statistic is the probability that, for a randomly chosen pair of people where one has an event and one doesn’t, the model gives the higher predicted risk to the one who has the event. A value of 0.5 is a coin flip and 1.0 is perfect ranking, and it measures only how well the model ranks people, not whether its absolute risk estimates are accurate.B) For net reclassification, CAC is pretty bad. Here, we go to the borderline risk group. About 1100 of the 6000 total participants. See Figure 4b in the paper. There were 40 ASCVD events. CAC moved 20 adults (50%) correctly up in risk, and 13 (33%) incorrectly moved down and left 7 unchanged. There were 1075 nonevents. Of these, CAC moved 61% correctly down in risk, and 26% incorrectly up in risk and left 13% unchanged. For the net in this borderline risk group, about 60% were reclassified correctly and 26% incorrectly. That means that if CAC reclassified you, it was correct in two thirds and incorrect in one third. That’s not good. My take home is that CAC adds very little to the PREVENT score. Prediction is hardly better, and net reclassification is pretty awful. I mean, it’s incorrect in a third of borderline risk adults. How is that a help? If people value reducing their ASCVD risk, they can take a statin. If they are on the fence, this study shows CAC hardly helps. You look at Figure 4b in that paper and tell me what I am seeing wrong about it. Conduction System Pacing vs Standard RV Pacing for AV block JAMA — not JAMA cardiology, but JAMA — has published a Chinese randomized controlled trial of conduction system pacing (CSP) vs right ventricular (RV) apical pacing.I realize it’s an EP topic, but gosh, it is JAMA. And pacing for atrioventricular (AV) block is an almost daily thing at my smallish hospital. If you present to Baptist Health Louisville, my hospital, with AV block, you will very likely receive a conduction system pacing lead. My partner and I preferentially use left bundle or His bundle pacing for patients with AV block. We believe that pacing the conduction system preserves right-to-left ventricular synchrony and avoids pacing induced cardiomyopathy. When successful, the paced QRS is a thing of shear beauty. It’s narrow. And gorgeous. Sometimes the nurse calls to say the pacer isn’t working because the QRS looks so normal. But of course beauty is not an outcome. And my medical conservative colleagues rightly say: John, where is your data. RV pacing has been done for like 50 years. And pacing-induced cardiomyopathy occurs in less than 20% of cases. And for those who have it you can upgrade to biV pacing, or leave alone if asymptomatic on guideline-directed medical therapy.The medical conservatives are correct; we should have data. And the LEAP-Block trial adds to the few trials done in this space. This was a multicenter trial in China. About 500 patients with AV block and normal ejection fraction were randomized to CSP or standard RV apical pacing. The primary endpoint was a composite of death, HF events, or upgrade to biV pacing. Results Left bundle-branch area pacing (LBBAP) significantly reduced the primary endpoint vs RVP (2.4% vs 12.5%, respectively; absolute risk difference, −10.1% P = .003).Among secondary outcomes, the LBBAP group had fewer HF events (3.4% vs 11.3%; −7.9%; 95% CI, −13.0% to −2.8%).No significant differences were observed in all-cause death, biventricular pacing upgrade, device-related complications, or pacing-induced cardiomyopathy.The 24-month Kaplan-Meier estimated cumulative incidence of the primary endpoint was 5.0% for LBBAP vs 13.2% for RVP (hazard ratio, 0.37; 95% CI, 0.19-0.73; P = .004).LBBAP superiority was consistent across all prespecified subgroups.My Comments I have to be careful here because of my bias — that is my love of CSP. While this is clearly a positive trial with a large absolute risk reduction in an important endpoint, there are reasons to be super cautious with this trial. Let me be hard on it, on purpose, to counter my bias — and as an exercise in critical appraisal. Let me talk about seven aspects of this that are important:The trial was unblinded, and driven by HF events, which are, as I have said many times, open to human nature bias. And in this trial, HF events were quite easy to trigger. Even edema got counted.There were no differences in harder, less-biased endpoints of biV upgrade or death.Pacing-induced cardiomyopathy was lower in the CSP arm (3.4% vs 7.4%) but did not reach statistical significance. And overall ejection fractions were close.You also worry about an implausibly large effect size, from only 43 events. Be cautious.Baseline imbalances all favored LBBAP. Compared with LBBAP patients, the RV pacing arm had older age (68.0 vs 65.2 years), more diabetes (24% vs 19%) higher NT-proBNP (median 316 vs 247), more NYHA class III (8.8% vs 6.2%), more paroxysmal AF and more hypertension.Post-randomization exclusions were labeled as intention-to-treat. There were 17 randomized patients (7 vs 10) who never got a pacemaker and were excluded. That is a modified intention-to-treat (ITT) analysis, not true ITT as the paper states. Why would patients with AV block requiring pacing not get a device? It suggests randomization happened well before the procedure, and these reasons aren’t described.Control-arm programming may have exaggerated RV pacing harm. About 10% of patients had first-degree AV block (PR ≥ 250 ms), and some had intermittent block. The protocol called for a fixed AV delay of 150–180 ms, which forces ventricular pacing in many of these patients. Thus, the 99% pacing burden in both arms suggests no attempt to minimize RV pacing where intrinsic conduction was possible. Programming that was more nuanced may have minimized harm from RV pacing. Maybe.I will cite a recent meta-analysis published in the Canadian Journal of Cardiology. It looked at 15 RCTs of CSP and RV pacing, many of which looked at surrogate outcomes, but some trials measured pacing-induced cardiomyopathy. This meta-analysis found a reduction in pacing-induced cardiomyopathy as well as heart failure hospitalization (HHF) with CS pacing, but the risk of bias was high in many of these trials. And the HHF metric was sensitive to removing one trial of patients with mildly reduced HF. In sum, the parameters and reliability of left bundle branch pacing has been great in our hospital. Unlike His-bundle pacing, thresholds are stable and good, and lead revisions are rare. Left bundle branch pacing isn’t always a perfect conduction system capture, but it’s often close, and we are not seeing anywhere near the numbers of upgrades. I realize that is anecdote, but our experience is similar to what is seen in the topline results of LEAP-Block, but the story is not yet done. When I was in the UK, many were skeptical of CSP, and I am open to being wrong. Though, like Charles Barkley famously said (and wrote a book): I may be wrong but I doubt it.