Cardiac contractility modulation: an update

Cardiac contractility modulation (CCM) represents an innovative device-based therapy for patients with heart failure (HF) who remain symptomatic despite optimal guideline-directed medical therapy (GDMT). It delivers biphasic, non-excitatory electrical signals during the absolute refractory period, enhancing myocardial contractility and relaxation. It improves calcium cycling and facilitates diastolic calcium reuptake. Therapeutic effects from key clinical studies and real-world experiences in HF with reduced ejection fraction (HFrEF) are reviewed and the safety profile is examined. The design and objectives of the ongoing AIM HIGHer clinical trial in HF patients with mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction are summarized. The design of the next-generation device combining CCM with defibrillator functionality (CCM-D) is presented. The objectives of the ongoing clinical study with CCM‑D, INTEGRA‑D, are discussed in detail.