Conduction System Pacing Falls Short of Biventricular Pacing in HFrEF With LBBB

Although conduction system pacing (CSP) has emerged as a potential alternative to traditional biventricular pacing (BiVP) for cardiac resynchronization therapy, particularly in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB),¹ this newer approach may not yet be ready to replace standard therapy, according to new findings.

The randomized clinical trial is published in JAMA Cardiology.

“In patients with symptomatic HFrEF and LBBB, CSP was inferior to BiVP on a hierarchical composite outcome of all-cause death, heart failure events, and change in LVEF [left ventricular ejection fraction] at 12 months,” wrote the researchers of the study. “The odds of a worse heart failure–related outcome were approximately 2-fold higher with CSP compared with BiVP, driven by a higher incidence of clinical events as well as a lesser improvement in LVEF.”

The study enrolled 173 patients across 14 hospitals in Brazil between November 2022 and December 2023. Eligible participants had symptomatic HFrEF, LVEF of 35% or less, and LBBB with a QRS duration of at least 130 milliseconds. Patients were randomized 1:1 to receive either CSP—preferentially left bundle-branch area pacing—or BiVP, with 12 months of follow-up.

The study’s primary end point was a hierarchical composite of all-cause death, heart failure hospitalizations, urgent heart failure visits, and change in LVEF at 12 months. CSP failed to meet the prespecified criteria for noninferiority and was found inferior to BiVP. The OR for the primary outcome was 2.36 (95% CI, 1.37-4.06; P = .002 for between-group difference), indicating significantly worse outcomes among patients receiving CSP.

Further analysis showed that the time-to-event composite outcome—including death, heart failure hospitalization, or urgent visits—was also higher in the CSP group, with an HR of 2.35 (95% CI, 0.99-5.61).

Cardiac function improvements were observed in both groups, but BiVP demonstrated a greater increase in LVEF. At 12 months, mean LVEF rose to 35% in the CSP group compared with 39% in the BiVP group, yielding a statistically significant mean difference of 3.8% (95% CI, 0.3%-7.3%). Despite these differences, both groups experienced similar improvements in secondary measures, including QRS duration, Kansas City Cardiomyopathy Questionnaire scores, New York Heart Association class, and natriuretic peptide levels.

One notable advantage of CSP was cost. Total direct medical costs, including the procedure and subsequent heart failure care, were approximately $7090 lower per patient in the CSP group over 12 months. This finding highlights CSP’s potential economic appeal, particularly in resource-constrained settings. However, the cost savings did not offset the observed differences in clinical outcomes.

However, the researchers noted several limitations, including variability in care across sites and limited operator experience with CSP, which may reflect a learning curve. Its moderate sample size and low event rates also raise the possibility of random variation. Additionally, excluding patients eligible for implantable cardioverter-defibrillators limits generalizability.

These findings add to a growing and somewhat conflicting body of evidence on CSP. Notably, a separate randomized trial found that left bundle-branch pacing, a form of CSP, significantly reduced the risk of death or heart failure hospitalization compared with biventricular pacing (8% vs 28%; HR, 0.26; P < .001), with benefits largely driven by fewer hospitalizations.² In contrast, this trial showed worse outcomes with CSP, suggesting that the effectiveness of CSP may vary depending on patient selection, operator experience, and specific pacing techniques, underscoring the need for further large-scale, standardized trials to clarify its role in heart failure management.

“In the PhysioSync-HF randomized clinical trial among patients with HFrEF and LBBB, CSP failed to meet noninferiority and was inferior to BiVP for a composite of all-cause death, heart failure hospitalizations, urgent visits for heart failure, and LVEF change at 12 months,” wrote the researchers.¹

References

1. Zimerman A, dal Forno A, Rohde LE, et al. Conduction system vs biventricular pacing in heart failure. JAMA Cardiol. Published online March 11, 2026. doi:10.1001/jamacardio.2026.0101

2. Steinzor P. Left bundle-branch pacing reduces heart failure hospitalization vs biventricular pacing. AJMC^®. March 11, 2026. Accessed March 23, 2026. https://www.ajmc.com/view/left-bundle-branch-pacing-reduces-heart-failure-hospitalization-vs-biventricular-pacing