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 VO 2), 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 VO 2 alone (n = 60), there was an additional single arm non-randomized trial (FIX-HF-5C2) with a prospective comparison of its 24 week peak VO 2 data compared with the control group of the FIX-HF-5C control patients. Pooled analysis showed that, compared with control, CCM significantly improved peak VO 2 (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 À7.85, 95% CI À10.76 to À4.94, P < 0.00001). As a sensitivity analysis, we excluded the FIX-HF-5C2 trial (only relevant for peak VO 2), 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.

Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function

“…A recently performed individual‐patient meta‐analysis of 861 patients from randomized trials of CCM therapy 7 also demonstrated improvements in peak VO 2 , 6‐ min walk distance, and quality of life, thus confirming the findings of the present study. Moreover, long‐term improvements in quality of life, as estimated by NYHA class and MLWHFQ, along with reductions in rates of hospitalization were seen in another analysis 8 of 140 patients with LVEF of 25–45% included in the European Union Registry of CCM therapy.…”

Long‐term clinical experience with cardiac contractility modulation therapy delivered by the Optimizer Smart system

“…This large and long-term registry confirms effectiveness and benefits of CCM with the results of prior shorter-term and smaller randomized and registry studies. 5,6 Similar improvements in functional status and quality of life were shown for the AF and LVEF subgroups. LVEF improvements were also seen in all subgroups, with the largest improvements in patients of the lowest LVEF subgroup (≤25%).…”

“…This large and long‐term registry confirms effectiveness and benefits of CCM therapy in patients with moderate to severe heart failure consistent with the results of prior shorter‐term and smaller randomized and registry studies. 5 , 6 …”

Exercise Training: The Holistic Approach in Cardiovascular Prevention

“…The core component of cardiac rehabilitation is the assessment of patient' class of risk [69] together with dietary advice [70,71], educational intervention [72,73], psychological support [74], exercise training [75] and therapy management [69]. Nowadays great progresses have been made in drug therapy [76][77][78][79][80], devices [81][82][83][84][85][86], and diagnostic technologies [87][88][89][90], which allow for an even greater reduction of some risk factors. However, to further reduce risk of new CV events, it is important to act not only on optimization of therapy and its adherence, but also on other risk factors such as OB and lifestyle [91][92][93].…”