This week in Cardiology

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Cardiology. This week we're covering 10 notable papers spanning earlier and broader use of structural heart intervention, how we image, diagnose and lower lipids in coronary disease, and new directions in conduction system pacing and hypertension therapy. Let's dive in.

Structural heart intervention keeps pushing into patients who used to be watched rather than treated, and three trials this week test that boundary. In the New England Journal of Medicine, Généreux and colleagues report the PROGRESS trial, which randomized 744 patients with moderate aortic stenosis and at least one at-risk feature, such as symptoms or structural or functional cardiac abnormalities, to transfemoral balloon-expandable TAVR or to guideline-style clinical surveillance [1]. These were older patients, mean age 78, with a mean valve area of 1.2 square centimetres. At two years, death or a heart failure event occurred in about 17 percent of the TAVR group versus about 24 percent of the surveillance group, an absolute reduction of roughly seven points that met the test for superiority. The detail worth holding onto is what drove it: heart failure events fell from about 19 percent to about 11 percent, while all-cause death was numerically slightly higher with TAVR, around 8 percent versus 7 percent. The trial was open label, heart failure events counted with or without hospitalization, and it was industry funded, so the benefit rests on a softer component, but it is the first randomized evidence that intervening before stenosis becomes severe changes outcomes. In Circulation, Gao and colleagues report SEASON-AR, a Chinese multicentre trial in 210 patients with severe pure aortic regurgitation who were poor surgical candidates or declined surgery [2]. TAVR with the VitaFlow system plus medical therapy cut the one-year composite of death, disabling stroke or heart failure rehospitalization by roughly two thirds compared with medical therapy alone, driven mainly by far fewer heart failure readmissions. That came at the cost of more major bleeding and more new pacemakers, mostly in the first month. It is a single dedicated valve platform in a modest-sized open-label trial, but it fills a gap where no adequately powered randomized data existed. On the mitral side, the Journal of the American Heart Association carries a retrospective Cedars-Sinai analysis by Nagasaka and colleagues of 826 patients with moderate or worse residual regurgitation after the first edge-to-edge repair clip [3]. Patients who received additional clips had greater regurgitation reduction and fewer deaths or heart failure hospitalizations at one year, about 17 percent versus 29 percent, without more complications, despite higher transmitral gradients. Being single-centre and observational, with a much smaller single-clip comparison group, it supports rather than proves a strategy of pursuing more complete reduction.

Staying with devices, the question of what to give patients after left atrial appendage closure has been answered largely by habit, and Reddy and colleagues in JAMA bring randomized data with the SIMPLAAFY trial [4]. Across 87 United States sites, 1857 patients were randomized to six months of dual antiplatelet therapy, three months of a reduced-dose non-vitamin K oral anticoagulant, or aspirin alone. Both simpler regimens were noninferior to dual antiplatelet therapy for the six-month composite of death, stroke, systemic embolism or major bleeding, and aspirin alone had roughly half the composite event rate of dual therapy. Major bleeding ran from about 4.5 percent with dual therapy to under 2 percent with aspirin alone, though bleeding and device thrombus were exploratory analyses. Device-related thrombus was lowest with the reduced-dose anticoagulant. The findings apply to uncomplicated procedures, and follow-up is only six months.

Our second theme is coronary disease, from the diagnostic pathway through to plaque biology and real-world lipid management. In the New England Journal of Medicine, Collet and colleagues report the P4 trial, randomizing 1105 patients with a significant lesion and a CT-derived fractional flow reserve of 0.80 or less to PCI planned with coronary CT angiography or guided by intravascular ultrasound [5]. Target-vessel failure at a year was about 4 percent in both arms, so the CT-guided strategy was noninferior but not superior. This suggests that a noninvasive anatomic and physiologic roadmap can stand in for intravascular imaging in this selected population, though the trial was funded by CT and software companies and one year is short for stent outcomes. Further upstream, Boeddinghaus and colleagues in The Lancet pooled individual patient data from all five randomized trials comparing the 0/1 hour and 0/3 hour troponin pathways, covering nearly 111,000 presentations [6]. Death or new type 1 infarction within 30 days was rare with both approaches, around one percent, and the pooled safety estimate was imprecise. Importantly, the faster pathway did not on average shorten emergency department stays or clearly increase direct discharge, and heterogeneity between trials was substantial. The authors note the primary safety outcome was refined after data receipt but before analysis, and they conclude that hospitals weighing a switch need to consider wider organisational factors, a sobering counterpoint to guideline enthusiasm for the 0/1 hour approach.

On lipids, JAMA Cardiology publishes prespecified imaging analyses from FLOWPROMOTE by Mortensen and colleagues [7]. In 104 statin-naive patients with newly diagnosed stable coronary disease, rosuvastatin 40 milligrams plus ezetimibe drove LDL cholesterol down by about two thirds, to around 43 milligrams per decilitre, versus about a 38 percent fall with atorvastatin 40 milligrams. The combination produced significantly greater regression of total and noncalcified plaque across the whole coronary tree, with noncalcified plaque regressing in nearly every patient on combination therapy, and lower achieved LDL tracked linearly with more regression. It is a small secondary analysis using imaging endpoints, not clinical events. The Journal of the American Heart Association adds the real-world flip side from Supriami and colleagues, who followed more than 250,000 new statin users at Mass General Brigham over 24 years [8]. About 4 percent of users developed documented intolerance, mostly muscle symptoms, and within 90 days roughly four in ten of those patients stopped all lipid-lowering therapy, while fewer than one in ten received a nonstatin strategy. Stopping everything was associated with higher risk across every outcome, up to roughly doubled risk for some events. These are observational associations open to confounding, but together with FLOWPROMOTE they frame a gap between what intensive lowering can achieve and what many intolerant patients actually receive.

Our final theme looks at newer therapeutic approaches in rhythm management and hypertension. In JAMA, Li and colleagues report LEAP-Block, a trial across 14 Chinese hospitals randomizing 499 patients with atrioventricular block, preserved ejection fraction and an expected ventricular pacing burden above 40 percent to left bundle-branch area pacing or conventional right ventricular pacing [9]. At 24 months, the composite of death, heart failure events or upgrade to biventricular pacing was cut by roughly two thirds with conduction system pacing, largely through fewer heart failure events. There were no significant differences in death, upgrades, device complications or pacing-induced cardiomyopathy individually, and left bundle capture was confirmed in about four in five patients. This is the most robust randomized outcome evidence so far for physiologic pacing in this group, though it comes from experienced Chinese centres and the composite is driven by one component. Also in JAMA Cardiology, Zhang and colleagues report a phase one study of ART101, a liver-targeted small interfering RNA against angiotensinogen [10]. A single injection reduced angiotensinogen by about 90 percent, with no serious adverse events or hyperkalaemia, and at 24 weeks a 600 milligram dose lowered placebo-corrected ambulatory systolic pressure by about 13 millimetres of mercury in healthy participants. With only 48 participants and exploratory blood pressure data, this is proof of concept for twice-yearly or less frequent dosing, not evidence of clinical benefit.

If you only have time for one paper this week, make it the PROGRESS trial in the New England Journal of Medicine [1]. It reopens the long-settled assumption that moderate aortic stenosis is a surveillance condition, while leaving open whether a benefit driven by heart failure events, without a mortality signal, justifies earlier valve replacement.

Here is what this week's evidence adds up to in Cardiology. First, randomized data now support TAVR beyond its classic indication, in moderate stenosis with at-risk features and in severe pure regurgitation, but both benefits rest mainly on heart failure endpoints from open-label trials, and durability and mortality questions remain. Second, after uncomplicated appendage closure, a single large trial supports simpler regimens, including aspirin alone, as noninferior to dual antiplatelet therapy over six months, with longer follow-up still needed. Third, a randomized trial now supports left bundle-branch area pacing over right ventricular pacing for high-burden pacing with preserved function, though generalisability beyond expert centres is unsettled. Fourth, in coronary disease, CT-guided PCI planning matched intravascular ultrasound at one year, and the faster troponin pathway did not deliver the expected efficiency gains on average. Finally, more intensive LDL lowering produced more plaque regression in a small imaging study, while observational data show that statin intolerance often ends in no therapy at all, a gap associated with worse outcomes.

That's your roundup for This Week in Cardiology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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