Outcomes of Cardiac Contractility Modulation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

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.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Copyright © 2019 Ramy Mando et al.

Figures

Figure 1

A flow diagram of the search strategy conducted. A flow diagram of the search strategy conducted. The purpose of this figure is to provide a graphical representation of the manner in which we conducted our search for RCT for CCM. PRISMA guidelines were followed.

Figure 2

Forest plot of all-cause mortality (postrandomization/device implantation). A forest plot of the data available to us from the 4 RCTs assessing all-cause mortality in those with CCM compared to those with OMT alone. There was a nonsignificant difference in the rate of total hospitalizations between the two groups.

Figure 3

Forest plot of total hospitalizations in the CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing total hospitalizations in those with CCM compared to those with OMT alone. There was a nonsignificant difference in the rate of total hospitalizations between the two groups.

Figure 4

Forest plot of worsening HF/HF-related hospitalizations in the CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing worsening HF and HF-related hospitalizations in those with CCM compared to those with OMT alone. There was a nonsignificant trend in reduced HF hospitalizations in those with CCM.

Figure 5

Forest plot of cardiac arrhythmias in CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing arrhythmias in those with CCM compared to those with OMT alone. There was a nonsignificant trend in reduced arrhythmic events favoring the OMT group.

Figure 6

Forest plot of pacemaker/ICD sensing defects/malfunction in CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing pacemaker/ICD sensing defects/malfunction in those with CCM compared to those with OMT alone. There was a nonsignificant trend in increased sensing defect and malfunction in the CCM group.

Figure 7

Forest plot of the six-minute walking distance in the CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing 6MWD in those with CCM compared to those with OMT alone. There was no statistically significant difference in 6MWD between these two groups.

Figure 8

Forest plot of the MLWHFQ in the CCM groups versus the control groups. A forest plot of the data available to us from the 4 RCTs assessing MLWHFQ in those with CCM compared to those with OMT alone. There was a statistically significant difference between these two groups favoring CCM.