Cardiac Contractility Modulation in Heart Failure Management

Cardiac contractility modulation (CCM) is an innovative device-based therapy designed to enhance myocardial performance in patients with heart failure, particularly those with reduced ejection fraction who remain symptomatic despite optimal medical therapy. Delivered via specialised intracardiac leads positioned on the right ventricular septum, CCM administers non-excitatory biphasic electrical impulses during the absolute refractory period. These signals improve calcium handling and promote reverse myocardial remodelling at the cellular level, restoring more physiological contractile properties. Clinically, CCM has been shown to relieve symptoms, improve exercise capacity and quality of life, and reduce hospital admission rates in New York Heart Association (NYHA) class III patients with left ventricular ejection fraction (LVEF) between 25 and 45 per cent. The therapy fills a critical gap for individuals who are ineligible for cardiac resynchronisation due to narrow QRS duration or non-response, addressing a sizeable subgroup of heart failure sufferers. Beyond symptomatic relief, emerging data suggest that CCM may confer sustained structural benefits, including improved global longitudinal strain and mechano-energetic efficiency, as well as favourable alterations in right ventricular function. Ongoing refinements in patient selection criteria and lead placement guided by imaging biomarkers aim to maximise therapeutic response and long-term outcomes. As device technology evolves, CCM holds global significance as a complementary approach in the comprehensive management of heart failure.

Research from Nature Portfolio

Recent studies have demonstrated that myocardial tissue characteristics at the lead implantation site are key determinants of CCM efficacy. Assessment of septal scar burden by late gadolinium enhancement cardiac magnetic resonance imaging has emerged as a powerful predictor of clinical response. Patients with scar involvement below a defined threshold exhibit more pronounced improvements in NYHA class and LVEF, whereas extensive septal fibrosis attenuates contractile gains. These findings underscore the value of pre-implant imaging to optimise lead positioning, refine candidate selection and enhance the likelihood of functional recovery.

Cardiac Contractility Modulation in Heart Failure Management publication trend

The graph below shows the total number of articles in cardiac contractility modulation in heart failure management across all publications each year (not limited to Nature Index journals).

Technical terms

Cardiac contractility modulation (CCM): A device therapy delivering electrical impulses to the ventricular septum during the refractory period to enhance myocardial contractile strength without inducing extra beats.

Ejection fraction (EF): The proportion of blood pumped out of the left ventricle with each heartbeat, expressed as a percentage of end-diastolic volume.

New York Heart Association (NYHA) classification: A functional scale grading heart failure severity based on the patient’s symptoms during physical activity.

Late gadolinium enhancement (LGE): An imaging method in cardiac magnetic resonance that highlights fibrotic or scarred myocardium after contrast administration.

Global longitudinal strain (GLS): A measure of myocardial deformation along the long axis of the left ventricle, reflecting contractile function.

Myocardial mechano-energetic efficiency (MEE): The ratio of mechanical work performed by the heart to the oxygen consumed, indicating energetic performance of the myocardium.

Reverse remodelling: The process by which pathological changes in ventricular size, shape and function are partially or fully reversed towards normal.

References

1. Cardiac contractility modulation: a novel approach for the treatment of heart failure. Heart Failure Reviews (2016).
2. Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction. Clinical Research in Cardiology (2017).
3. New Generation Cardiac Contractility Modulation Device—Filling the Gap in Heart Failure Treatment. Journal of Clinical Medicine (2019).
4. Effects of Cardiac Contractility Modulation Therapy on Right Ventricular Function: An Echocardiographic Study. Applied Sciences (2022).
5. The Effects of Device-Based Cardiac Contractility Modulation Therapy on Left Ventricle Global Longitudinal Strain and Myocardial Mechano-Energetic Efficiency in Patients with Heart Failure with Reduced Ejection Fraction. Journal of Clinical Medicine (2022).
6. Cardiac contractility modulation in patients with heart failure: The added value of cardiac rehabilitation in identification, management, and follow-up. International Journal of Cardiology Cardiovascular Risk and Prevention (2024).
7. Mid-term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation. Journal of Interventional Cardiac Electrophysiology (2024).
8. Septal myocardial scar burden predicts the response to cardiac contractility modulation in patients with heart failure. Scientific Reports (2022).