Biventricular Pacing Outperforms Conduction System Pacing in Heart Failure: Key Insights from PhysioSync-HF Trial

Background

Heart failure with reduced ejection fraction (HFrEF) accompanied by left bundle branch block (LBBB) presents a significant clinical challenge, affecting approximately 25-30% of HF patients. Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP) has been the gold standard, improving symptoms and survival. However, conduction system pacing (CSP), particularly left bundle branch area pacing, emerged as a potentially simpler and cost-effective alternative, though its comparative efficacy remained unproven until the PhysioSync-HF trial.

Study Design

This multicenter, noninferiority randomized clinical trial enrolled 173 adults across 14 Brazilian hospitals (November 2022-December 2023). Eligible participants had HFrEF (LVEF ≤35%), symptomatic NYHA class II-III, and LBBB (QRS ≥130ms). Patients were randomized 1:1 to CSP (preferentially left bundle-branch area pacing) or BiVP. The primary endpoint was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and LVEF change at 12 months, with a noninferiority margin OR of 1.2.

Key Findings

CSP failed to meet noninferiority and was statistically inferior to BiVP (OR 2.36; 95% CI 1.37-4.06; p=0.002). The CSP group showed:

• Higher composite of death/HF hospitalizations/urgent visits (HR 2.35; 95% CI 0.99-5.61)
• Smaller LVEF improvement (mean difference -3.8%; 95% CI 0.3-7.3%)
• Comparable QRS narrowing, symptom scores, and biomarker reductions
• Lower procedural/HF care costs ($7,090 savings; 95% CI $5,779-$8,648)

Expert Commentary

While CSP demonstrated cost advantages and preserved some CRT benefits, its inferiority in hard outcomes suggests BiVP remains superior for structural remodeling. Lead placement precision and procedural learning curves may have influenced results. The trial underscores the need for refined patient selection criteria if CSP is to be reconsidered in specific subgroups.

Conclusion

PhysioSync-HF provides definitive evidence against CSP as a first-line CRT strategy in HFrEF with LBBB. Clinicians should prioritize BiVP despite higher costs, while research continues to optimize CSP techniques and identify potential responder subgroups. The findings directly inform current guideline recommendations for device-based HF therapy.