Conduction System vs Biventricular Pacing in Heart Failure: The PhysioSync-HF Randomized Clinical Trial
André Zimerman1,2,3,4, Alexander Dal Forno5, Luis E Rohde1,2,3,4,6
1MOVE Academic Research Organization, Hospital Moinhos de Vento, Moinhos de Vento Medical School, Porto Alegre, Brazil.
Insights
Conduction system pacing (CSP) was inferior to biventricular pacing (BiVP) for heart failure outcomes in patients with heart failure with reduced ejection fraction and left bundle-branch block. These results do not support CSP as a first-line therapy.
Area of Science:
- Cardiology
- Electrophysiology
- Heart Failure Management
Background:
- Conduction system pacing (CSP) presents a potential alternative to biventricular pacing (BiVP) for heart failure patients with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB).
- The comparative efficacy of CSP versus BiVP on heart failure (HF) outcomes in this specific patient population remains incompletely understood.
- Investigating novel pacing strategies is crucial for optimizing treatment and improving outcomes in HFrEF patients with LBBB.
Purpose of the Study:
- To compare the effectiveness of CSP against BiVP in patients diagnosed with HFrEF and LBBB.
- To evaluate the impact of CSP versus BiVP on key heart failure-related clinical outcomes.
- To determine the noninferiority of CSP compared to BiVP for HF management in this cohort.
Main Methods:
- A multicenter, noninferiority randomized clinical trial (PhysioSync-HF) was conducted.
- Adult patients with symptomatic HFrEF (NYHA classes II-III), LVEF ≤35%, and LBBB (QRS ≥130 ms) were randomized 1:1 to CSP or BiVP.
- The primary outcome was a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months.
Main Results:
- CSP failed to demonstrate noninferiority and was found to be inferior to BiVP for the primary composite endpoint (OR, 2.36; P=.002).
- The composite of death, HF hospitalizations, or urgent HF visits occurred more frequently with CSP (HR, 2.35).
- While both pacing methods improved LVEF, QRS duration, and quality of life metrics, BiVP showed a statistically significant greater increase in LVEF.
- CSP was associated with lower direct medical costs compared to BiVP.
Conclusions:
- In patients with HFrEF and LBBB, CSP was inferior to BiVP regarding a composite of major HF events and LVEF change at 12 months.
- The study findings do not support the routine use of CSP as the initial resynchronization strategy for this patient group.
- Further research may be needed to identify specific subgroups who might benefit from CSP or to refine CSP techniques.
Importance:
Conduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain.
Objective:
To compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB.
Design, Setting, And Participants:
PhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninferiority randomized clinical trial enrolling participants from November 2022 to December 2023 with 12 months of follow-up at 14 hospitals across all regions of Brazil. Adults with symptomatic HFrEF (New York Heart Association NYHA] classes II through III), left ventricular ejection fraction (LVEF) of 35% or less, and LBBB (QRS duration ≥130 milliseconds) were eligible for inclusion. Data were analyzed from May to August 2025.
Intervention:
Patients were randomized 1:1 to either CSP (preferentially left bundle-branch area pacing) or BiVP.
Main Outcomes And Measures:
The primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. The prespecified noninferiority margin for the odds ratio (OR) was 1.2.
Results:
A total of 173 patients (median [IQR] age, 62 years [56-68]; 86 female patients [49.7%]; 115 (66.5%) with dilated cardiomyopathy; median [IQR] LVEF, 26% [22%-31%]; median [IQR] QRS, 180 milliseconds [170-200]) were included. At 12 months, CSP failed to meet noninferiority and was inferior to BiVP for the primary end point (OR, 2.36; 95% CI, 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The time-to-event composite of death, HF hospitalizations, or urgent HF visits was higher in CSP (hazard ratio, 2.35; 95% CI, 0.99-5.61). Mean (SD) LVEF increased to 35% (12%) with CSP and 39% (12%) with BiVP (mean difference, 3.8%; 95% CI, 0.3%-7.3%). Relative to baseline, both groups had comparable improvements in QRS duration, Kansas City Cardiomyopathy Questionnaire Overall Summary Score, NYHA class, and natriuretic peptide levels. Total direct medical cost related to the procedure and heart failure care was the equivalent of $7090 (95% CI, $5779-$8648) lower in patients randomized to CSP at 12 months.
Conclusions And Relevance:
In patients with HFrEF and LBBB, CSP was inferior to BiVP for a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. These findings do not support the routine use of CSP as the first-line resynchronization strategy in this population.
Trial Registration:
ClinicalTrials.gov Identifier: NCT05572736.
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