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Updated: Jun 25, 2025

Evaluation of Cardiac Contractility Modulation Therapy in 2D Human Stem Cell-Derived Cardiomyocytes
Published on: December 16, 2022
HF Etiology and cardiac contractility modulation therapy
Karapet Davtyan1, Ivan Chugunov1, Arpi Topchyan2
1National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.
Insights
Cardiac contractility modulation (CCM) therapy improved heart function in patients with heart failure with reduced ejection fraction (HFrEF). Non-ischemic HFrEF patients showed greater left ventricular ejection fraction (LVEF) improvement than ischemic patients, with similar survival rates.
Area of Science:
- Cardiology
- Heart Failure Research
- Medical Device Technology
Background:
- Heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge, necessitating advanced therapeutic strategies.
- Cardiac contractility modulation (CCM) therapy offers a potential treatment option for patients with HFrEF refractory to optimal medical therapy.
Purpose of the Study:
- To evaluate the safety and efficacy of CCM therapy in HFrEF patients, stratified by the etiology of heart failure (HF).
- To compare treatment outcomes between patients with ischemic (ICM) and non-ischemic (NICM) HFrEF undergoing CCM therapy.
Main Methods:
- A retrospective analysis of 166 patients with drug-resistant HFrEF who received CCM device implantation between 2013 and 2019.
- HF etiology was determined via coronary angiography or cardiac MRI. Outcomes including left ventricular ejection fraction (LVEF), 6-minute walking test (6MWT), and NYHA class were assessed at baseline and 12 months post-implantation.
Main Results:
- No significant difference in mortality was observed between the ICM (61.5%) and NICM (38.5%) groups.
- Patients with NICM demonstrated a significantly greater improvement in LVEF (7.7% vs. 2.0%, p < 0.001) and LV reverse remodeling compared to ICM patients at 12 months.
- Improvements in 6MWT and NYHA class were not significantly different between the groups, though factors like atrial fibrillation and COPD were associated with poorer NYHA class improvement.
Conclusions:
- CCM therapy is a viable option for drug-resistant HFrEF, with no significant difference in survival based on HF etiology.
- Patients with non-ischemic HFrEF experience superior improvements in LVEF and LV reverse remodeling following CCM implantation compared to those with ischemic HFrEF.
Objectives:
Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology.
Methods:
We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation.
Results:
The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032).
Conclusion:
In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.
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