Conduction system pacing (CSP), including left bundle-branch area pacing, is being evaluated as an alternative to biventricular pacing (BiVP) for cardiac resynchronization in heart failure with reduced ejection fraction (HFrEF). The PhysioSync-HF randomized clinical trial, published in JAMA Cardiology, evaluated whether CSP is noninferior to BiVP for heart failure outcomes in patients with HFrEF and left bundle-branch block (LBBB).

This investigator-initiated, multicenter, randomized clinical trial enrolled 173 adults across 14 hospitals in Brazil between November 2022 and December 2023, with 12-month follow-up. Eligible participants had symptomatic HFrEF (New York Heart Association [NYHA] class II–III), left ventricular ejection fraction (LVEF) ≤35%, and LBBB with QRS duration ≥130 milliseconds. Patients were randomized 1:1 to CSP or BiVP. The primary endpoint was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF, with a prespecified noninferiority margin of 1.2 for the odds ratio (OR).

At 12 months, CSP did not meet noninferiority and was inferior to BiVP for the primary endpoint (OR 2.36; 95% confidence interval [CI]: 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The composite of death, HF hospitalization, or urgent HF visits occurred more frequently in the CSP group (hazard ratio: 2.35; 95% CI: 0.99-5.61). LVEF improved in both groups but was greater with BiVP (39% vs 35%; mean difference: 3.8%; 95% CI: 0.3%-7.3%). Improvements in QRS duration, NYHA class, Kansas City Cardiomyopathy Questionnaire score, and natriuretic peptide levels were similar. Total direct medical costs were lower with CSP by $7090 (95% CI: $5779-$8648).

CSP was associated with worse outcomes compared with BiVP despite lower costs. These findings do not support routine use of CSP as a first-line resynchronization strategy in this population.