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Updated: Jun 12, 2025
Evaluation of Cardiac Contractility Modulation Therapy in 2D Human Stem Cell-Derived Cardiomyocytes
Published on: December 16, 2022
Cardiac contractility modulation in heart failure with reduced ejection fraction patients with QRS duration 120-149
Christian Fastner1, Niraj Varma2, Ishu Rao3
1Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, European Center for AngioScience (ECAS), and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany.
Background:
A subset of heart failure with reduced ejection fraction (HFrEF) patients qualifies for cardiac resynchronization therapy (CRT). However, a 30% CRT nonresponder rate persists, with patients having narrower QRS durations (ie, QRSd 120-149 ms) receiving less or inconsistent benefit. Cardiac contractility modulation (CCM) may be an important alternative therapy option but has largely been evaluated only in HFrEF patients with QRSd <120 ms.
Objectives:
The purpose of this study was to evaluate the impact of CCM on HF-related hospitalizations and on left ventricular ejection fraction (LVEF) as well as quality of life in HFrEF patients with QRSd 120-149 ms compared to QRSd <120 ms.
Methods:
The CCM-REG Registry enrolled a total of 503 HFrEF patients with follow-up up to 2 years. Hospitalization rates were available for 1 year preimplant. Safety was assessed by comparison of actual vs Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score- or Seattle Heart Failure Model (SHFM)-predicted mortality.
Results:
Among 111 of 455 patients with QRSd 120-149 ms (mean QRSd 130 ± 9 ms; 20% female; age 68 ± 11 years; LVEF 29% ± 9%; 82% New York Heart Association [NYHA] class III), CCM diminished HF-related hospitalization rate by 72% (pre- vs postimplant 0.90 vs 0.25 events per patient-year over 2 years; P <.001). LVEF improved by 7% ± 9% (P = .014 vs baseline), Minnesota Living with Heart Failure Questionnaire score by 10 ± 23 points (P = .010 vs baseline), and NYHA class by 0.5 ± 0.7 classes (<0.001 vs baseline). The effect sizes were similar to those in QRSd <120 ms patients. Mortality within the first year was 19% in QRSd 120-149 ms patients (ie, not significantly different from the MAGGIC risk score or SHFM prediction).
Conclusions:
CCM significantly improved HF control in NYHA class III HFrEF with reduced ejection fraction patients with moderately prolonged QRSd of 120-149 ms. The effect was comparable to that in patients with QRSd <120 ms.
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