Cardiac Contractility Modulation: a Novel Adjunctive Therapy for Heart Failure Patients Undergoing Treatment with Implantable Cardioverter Defibrillators

This paper aims to clarify the mechanism of action of Cardiac Contractility Modulation in heart failure treatment, synthesize key clinical evidence supporting the combination of Cardiac Contractility Modulation and implantable cardioverter-defibrillators for managing heart failure with reduced ejection fraction, and explore potential challenges and future applications pertaining to this combined therapy.

Recent studies indicate that cardiac contractility modulation therapy improves ventricular function without elevating myocardial oxygen consumption, promotes recovery of diastolic and systolic function, augments myocardial contractility, and exhibits substantial efficacy in drug-refractory chronic heart failure. Additionally, cardiac contractility modulation markedly improves left ventricular function, reduces hospitalization frequency, and enhances quality of life in patients with heart failure with reduced ejection fraction and a QRS duration of 120–149 ms. It may also serve as a pivotal strategy to arrest progression of heart failure with preserved ejection fraction. Combining implantable cardioverter-defibrillators with cardiac contractility modulation addresses a critical gap in the clinical management of patients with heart failure with reduced ejection fraction. These individuals meet criteria for left ventricular assist devices but are ineligible for cardiac resynchronization therapy and fail to derive long-term survival benefits from implantable cardioverter-defibrillator monotherapy.

This review demonstrates that combining cardiac contractility modulation and implantable cardioverter-defibrillators shows potential for improving outcomes in specific populations with heart failure with reduced ejection fraction by addressing limitations of single-therapy approaches. A key implication is that this combined strategy may offer a valuable therapeutic option for patients underserved by current guidelines. However, further rigorous clinical investigations are needed to fully establish its long-term efficacy, safety, and optimal patient selection criteria. These findings highlight the need for future research to refine the application of this combined therapy and expand its evidence base, which may inform future treatment guidelines for heart failure with reduced ejection fraction.

(Created in BioRender. Marina, T. (2025) https://BioRender.com/l82n523)

Full size image