Cardiac contractility modulation therapy: Molecular mechanisms and rationale for clinical application in heart failure with systolic and diastolic dysfunction

This review illustrates the pathophysiological aspects and available scientific evidence on molecular mechanisms about cardiac contractility modulation (CCM) therapy. The main advances in understanding the effect of this electrical therapy at cellular level in the heart are critically discussed in light of the data from clinical trials supporting the use of CCM therapy in patients with heart failure across a wide range of left ventricular ejection fraction values. This electrical therapy triggers a physiological cellular response leading to an improvement of cardiac performance and reverse ventricular remodeling, with no increase in oxygen consumption. The present review deals with the new potential applications of CCM for patients with chronic heart failure and paves the way for the development of a longitudinal Italian registry of patients implanted with this cardiac device.