Related Experiment Video

Updated: Jun 24, 2026

Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing
12:45

Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing

Published on: December 11, 2017

Comprehensive clinical benefit of CCM in HFrEF patients: a win-ratio analysis of FIX-HF-5C randomized trial

Rami Kahwash1, Poying Lai2, William T Abraham3

  • 1Division of Cardiovascular Medicine, The Ohio State University Medical Center, 473W 12th Avenue, Suite 200, Columbus, OH 43210-1252, USA.

ESC Heart Failure
|June 23, 2026
PubMed

Insights

Cardiac contractility modulation (CCM) therapy significantly improved heart failure outcomes, enhancing patient quality of life and functional capacity. A win-ratio analysis confirmed CCM

Area of Science:

  • Cardiology
  • Heart Failure Management
  • Clinical Trials

Background:

  • The FIX-HF-5C study showed Cardiac Contractility Modulation (CCM) therapy improved patient-centered outcomes in heart failure.
  • Reductions in cardiovascular death and heart failure hospitalization (HFH) were observed but not primary endpoints.
  • A win-ratio method was used to re-analyze CCM's comprehensive clinical benefit, integrating event-driven and patient-centered outcomes.

Purpose of the Study:

  • To re-analyze the comprehensive clinical benefit of CCM therapy using a win-ratio method.
  • To integrate event-driven clinical endpoints with patient-centered outcomes for a holistic assessment.
  • To evaluate CCM therapy's effectiveness in patients with NYHA Class III versus IV heart failure.

Main Methods:

  • A hierarchical win-ratio analysis prioritized cardiovascular mortality, HFH, and patient-centered outcomes.
  • Patient-centered outcomes included peak oxygen consumption, quality of life (MLHFQ), 6-minute walk distance, and NYHA functional class.
  • Sub-group analyses were conducted for patients with NYHA Class III versus IV.

Main Results:

  • The overall win ratio was 2.48, indicating a 71% pairwise probability of clinical benefit with CCM over optimal medical therapy (OMT).
  • Patient-centered outcomes contributed 56.2% to the wins, while event-driven endpoints accounted for 22%.
  • CCM consistently outperformed OMT across all hierarchies, with consistent effects observed in NYHA Class III and IV subgroups.

Conclusions:

  • The win-ratio re-analysis supports CCM therapy's consistent clinical benefit over OMT, integrating diverse outcome measures.
  • Findings demonstrate CCM's efficacy across a hierarchical framework including both hard clinical events and patient-reported outcomes.
  • While encouraging, these results are hypothesis-generating and require validation in future confirmatory studies.
Abstract

Keywords:
Cardiac Contractility Modulation (CCM)Composite endpointHeart Failure (HF)Left Ventricular Ejection Fraction (LVEF)NYHA

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