A comprehensive individual patient data meta-analysis of the effects of cardiac contractility modulation on functional capacity and heart failure-related quality of life

Abstract

Aims: Cardiac contractility modulation, also referred to as CCM™, has emerged as a promising device treatment for heart failure (HF) in patients not indicated for cardiac resynchronization therapy. We performed a comprehensive individual patient data meta-analysis of all non-confounded prospective randomized controlled trials of CCM vs. control that have measured functional capacity and/or quality of life questionnaires in patients with HF.

Methods and results: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in January 2020 to identify eligible randomized controlled trials. We also asked the sole manufacturer of the device for their list of known trials. Primary outcomes of interest were peak oxygen consumption (peak VO₂ ), 6 min walk test distance, and quality of life measured by Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and all data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Five trials were identified, four randomized studies enrolling 801 participants for all endpoints of interest, and for peak VO₂ alone (n = 60), there was an additional single arm non-randomized trial (FIX-HF-5C2) with a prospective comparison of its 24 week peak VO₂ data compared with the control group of the FIX-HF-5C control patients. Pooled analysis showed that, compared with control, CCM significantly improved peak VO₂ (mean difference +0.93, 95% CI 0.56 to 1.30 mL/kg/min, P < 0.00001), 6 min walk test distance (mean difference +17.97, 95% CI 5.48 to 30.46 m, P = 0.005), and quality of life measured by MLWHFQ (mean difference -7.85, 95% CI -10.76 to -4.94, P < 0.00001). As a sensitivity analysis, we excluded the FIX-HF-5C2 trial (only relevant for peak VO₂ ), and the result was similar, mean difference +0.65, 95% CI 0.21 to 1.08 mL/kg/min, P = 0.004.

Conclusions: This comprehensive meta-analysis of individual patient data from all known randomized trials has shown that CCM provides statistically significant and clinically meaningful benefits in measures of functional capacity and HF-related quality of life.

Keywords: 6 min walk test; Cardiac contractility modulation; Individual patient data meta-analysis; Minnesota Living with Heart Failure Questionnaire; OPTIMIZER™ device; Peak oxygen consumption.

Figure 1

Study selection presented in a flow diagram as depicted by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) statement.

Figure 2

Forest plots for changes in peak oxygen consumption (peak VO₂) (mL/kg/min) (panel A); in 6 min walk test (6MWT) distance (panel B); and in Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score (panel C). CCM, cardiac contractility modulation; CI, confidence interval; SD, standard deviation.