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Updated: Jan 3, 2026
Evaluation of Cardiac Contractility Modulation Therapy in 2D Human Stem Cell-Derived Cardiomyocytes
Published on: December 16, 2022
Outcomes of Cardiac Contractility Modulation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Ramy Mando1, Akshay Goel2, Fuad Habash2
1Department of Internal Medicine, Beaumont Health System, Royal Oak, MI, USA.
Insights
Cardiac contractility modulation (CCM) therapy improved quality of life for heart failure patients. However, it showed no significant benefits in exercise capacity, hospitalizations, or mortality, with a trend toward device issues.
Area of Science:
- Cardiology
- Medical Devices
- Heart Failure Management
Background:
- Cardiac contractility modulation (CCM) is an emerging device therapy for systolic heart failure (HF) in patients with narrow QRS complexes.
- Previous studies suggest potential benefits, necessitating an updated meta-analysis of randomized clinical trials (RCTs) to evaluate its efficacy and safety.
Purpose of the Study:
- To conduct an updated systematic review and meta-analysis of RCTs assessing the efficacy and safety of CCM therapy in heart failure patients.
- To evaluate the impact of CCM on key clinical outcomes including exercise capacity, quality of life, hospitalizations, and mortality.
Main Methods:
- A systematic review and meta-analysis of RCTs published between January 2001 and June 2018.
- Key outcomes analyzed included peak oxygen consumption (peak VO2), 6-Minute Walk Distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ), hospitalizations, arrhythmias, and mortality.
- Data were synthesized using standardized mean differences (SMD) and odds ratios (OR).
Main Results:
- Four RCTs with 801 patients (394 in the CCM group) were included in the analysis.
- CCM therapy demonstrated a significant improvement in MLHFQ scores (SMD -0.69, p = 0.0008).
- No significant differences were observed in 6MWD, HF hospitalizations, arrhythmias, all-cause hospitalizations, or all-cause mortality between CCM and control groups. A trend towards increased pacemaker/ICD malfunction was noted (OR 2.23, p = 0.06).
Conclusions:
- Short-term CCM therapy may enhance quality of life (MLHFQ) in heart failure patients.
- Current evidence does not support significant improvements in exercise capacity, hospitalizations, or mortality.
- A trend towards increased device-related complications warrants further investigation in larger, longer-term RCTs.
Background:
Cardiac contractility modulation (CCM) is a device therapy for systolic heart failure (HF) in patients with narrow QRS. We aimed to perform an updated meta-analysis of the randomized clinical trials (RCTs) to assess the efficacy and safety of CCM therapy.
Methods:
We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) between January 2001 and June 2018. Outcomes of interest were peak oxygen consumption (peak VO2), 6-Minute Walk Distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ), HF hospitalizations, cardiac arrhythmias, pacemaker/ICD malfunctioning, all-cause hospitalizations, and mortality. Data were expressed as standardized mean difference (SMD) or odds ratio (OR).
Results:
Four RCTs including 801 patients (CCM n = 394) were available for analysis. The mean age was 59.63 ± 0.84 years, mean ejection fraction was 29.14 ± 1.22%, and mean QRS duration was 106.23 ± 1.65 msec. Mean follow-up duration was six months. CCM was associated with improved MLWHFQ (SMD -0.69, p = 0.0008). There were no differences in HF hospitalizations (OR 0.76, p = 0.12), 6MWD (SMD 0.67, p = 0.10), arrhythmias (OR 1.40, p = 0.14), pacemaker/ICD malfunction/sensing defect (OR 2.23, p = 0.06), all-cause hospitalizations (OR 0.73, p = 0.33), or all-cause mortality (OR 1.04, p = 0.92) between the CCM and non-CCM groups.
Conclusions:
Short-term treatment with CCM may improve MLFHQ without significant difference in 6MWD, arrhythmic events, HF hospitalizations, all-cause hospitalizations, and all-cause mortality. There is a trend towards increased pacemaker/ICD device malfunction. Larger RCTs might be needed to determine if the CCM therapy will be beneficial with longer follow-up.
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