Cardiac muscle contractility modulation

Cardiac muscle contractility modulation refers to a therapy, not a discrete molecule or receptor. It uses an implantable device to deliver non-excitatory electrical signals to the heart muscle, specifically during the absolute refractory period of the cardiac cycle. This intervention increases cardiac contractility primarily by enhancing calcium handling in cardiomyocytes and inducing positive changes in cardiac gene expression and cellular metabolic pathways. It is used as an adjunctive treatment in patients with moderate-to-severe heart failure and reduced ejection fraction who remain symptomatic despite optimal medical therapy, especially those who are not candidates for cardiac resynchronization therapy. The therapy is delivered by dedicated devices such as the Optimizer system and does not refer to a single molecular or receptor target[1][2][4][7][8][9].

Other names

Cardiac contractility modulationCCM therapyCardiac muscle contractility modulation therapy

Device delivers non-excitatory biphasic high‐voltage signals to the ventricular septum during the absolute refractory period[7]. Increases myocardial contractile force by promoting calcium influx and sarcoplasmic reticulum calcium handling in cardiomyocytes[2][5]. Induces acute and chronic changes in gene expression and protein phosphorylation, improving myofilament sensitivity and cellular metabolism[3][2]. Promotes reverse remodeling of myocardium and partial restoration of abnormal gene expression seen in heart failure[1].