Cardiology

Aficamten delivers broad multidomain benefits vs metoprolol in obstructive HCM

MAPLE-HCM randomized 175 symptomatic obstructive HCM patients with significant LVOT gradients to aficamten or metoprolol for 24 weeks. Aficamten was superior for LVOT gradient reduction, NYHA class, KCCQ-CSS, NT-proBNP, peak VO2, and left atrial volume index. Numbers needed to treat versus metoprolol ranged from 1.5 to 5.0 across individual efficacy outcomes, indicating large absolute effects. Overall, 78% of aficamten patients were positive or complete multidomain responders vs 3% with metoprolol. 1

Sacubitril/valsartan adds biomarker benefit but not clinical gain in Chagas HFrEF

This open-label multicenter trial randomized 922 patients with HFrEF due to Chagas disease to sacubitril/valsartan or enalapril. Over a median 25.2 months, cardiovascular death and first HF hospitalization were similar between groups in the hierarchical composite. Sacubitril/valsartan produced a larger median NT-proBNP reduction at 12 weeks than enalapril and a stratified win ratio of 1.52 (95% CI, 1.28-1.82). Despite biomarker improvement, no significant advantage in clinical outcomes emerged for sacubitril/valsartan vs enalapril. 2

Nanosecond PFA noninferior to RF for paroxysmal AF, with shorter procedures

InsightPFA randomized 287 patients with paroxysmal AF to nanosecond pulsed field ablation (nsPFA) or ablation index–guided RF for PVI. Freedom from atrial tachyarrhythmia at 12 months off class I/III antiarrhythmics was similar, meeting noninferiority for nsPFA. Acute PVI success was 100% in both arms, with comparable procedure-related adverse event rates. NsPFA significantly reduced total procedure time, left atrial dwell time, and ablation time but increased fluoroscopy time and radiation exposure. 3

GLP-1–based therapies modestly lower AF risk in overweight or obesity

This meta-analysis pooled 24 randomized trials including 40,694 overweight or obese participants receiving GLP-1 receptor agonists or co-agonists vs placebo. GLP-1–based therapy reduced incident AF by 18% (RR 0.82; 95% CI, 0.70-0.96) with no between-trial heterogeneity (I2 = 0%). Risk reduction was consistent across single, dual, and triple agonists, individual drugs, BMI strata, diabetes status, and trial designs. Meta-regression showed no significant effect modification by weight loss magnitude or SGLT2 inhibitor use. 4