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Updated: Feb 2, 2026
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond
Carsten Tschöpe1,2,3, Behrouz Kherad1, Oliver Klein1,2,3
1Department of Cardiology, Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany.
Insights
Cardiac Contractility Modulation (CCM) therapy improves heart failure symptoms and reduces hospitalizations in patients with reduced ejection fraction (HFrEF). This innovative treatment shows promise across the spectrum of heart failure with mid-range (HFmrEF) and preserved ejection fraction (HFpEF).
Area of Science:
- Cardiology
- Biomedical Engineering
Background:
- Heart failure (HF) presents a significant global health burden with increasing prevalence and substantial morbidity/mortality.
- Despite advances in treating heart failure with reduced ejection fraction (HFrEF), outcomes remain suboptimal.
- Cardiac Contractility Modulation (CCM) therapy offers a novel approach to managing HF.
Purpose of the Study:
- To review the preclinical and clinical evidence for CCM in HFrEF and HFmrEF.
- To explore the potential application of CCM in heart failure with preserved ejection fraction (HFpEF).
- To highlight CCM's role in addressing unmet needs in HF treatment across ejection fraction ranges.
Main Methods:
- Review of preclinical and clinical literature on CCM therapy.
- Analysis of CCM's effects on cellular mechanisms, including calcium handling and reverse remodeling.
- Evaluation of CCM's impact on patient outcomes like symptoms, exercise tolerance, quality of life, and hospitalization rates.
Main Results:
- CCM therapy has demonstrated improvements in symptoms, exercise tolerance, and quality of life in HFrEF patients (EF 25-45%).
- CCM reduces HF hospitalizations and shows particular benefit in patients with baseline EF between 35-45% (HFmrEF).
- Cellular effects include improved calcium handling, reversal of the fetal gene program, and reverse remodeling in HFrEF.
Conclusions:
- CCM therapy is approved in several regions for symptomatic HFrEF patients with normal/prolonged QRS duration.
- CCM shows significant promise for HFmrEF and may offer a new therapeutic option for HFpEF.
- CCM has the potential to address critical unmet needs in the comprehensive management of heart failure across all ejection fraction categories.
Abstract:
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.
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