Send to

Choose Destination
Eur J Heart Fail. 2019 Jan;21(1):14-22. doi: 10.1002/ejhf.1349. Epub 2018 Nov 28.

Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond.

Author information

Department of Cardiology, Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany.
Berlin Center for Regenerative Therapies (BCRT), Campus Virchow Klinikum (CVK), Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
Department of Neurology, Universitätsmedizin Berlin, CVK, Berlin, Germany.
Medical College of Wisconsin, Milwaukee, WI, USA.
Cardiovascular Research Foundation, New York, NY, USA.
Department of Cardiovascular Physiology, Ruhr University Bochum, Bochum, Germany.


Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.


Cardiac contractility modulation; Heart failure; Pathophysiology; Preserved ejection fraction; Treatment


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center