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

Abstract

Aims Increasing attention is being given to patients with heart failure and ‘mid‐range’ left ventricular ejection fraction (LVEF, ≥40% and <50%) for whom there are no approved therapies that improve prognosis. We aim to assess for the first time the effects of cardiac contractility modulation (CCM) therapy in this patient population. Methods and results We assessed the effects of 6‐ month CCM therapy on functional status, exercise tolerance and quality of life in a subgroup of 53 patients with a LVEF of 40–45% recruited in previous CCM studies, including 37 patients in the CCM group and 16 in the control group. New York Heart Association classification improved by ≥1 class from baseline to 24 weeks in 80.6% (95% confidence interval [62.5%, 92.5%]) of patients in the CCM group compared with 57.1% in the control group (95% confidence interval [28.9%, 82.3%], P = 0.15). Six‐minute walk distance increased significantly in the CCM group with a net between‐group treatment effect of 53.9 ± 74.2 m (P = 0.05). Peak VO2 improved in the CCM group with a net between‐group treatment effect of 2.0 ± 2.8 mL/kg/min (P = 0.02). Minnesota Living with Heart Failure Questionnaire score decreased from baseline to 24 weeks with a net between‐group treatment effect of −13.1 ± 21.0 (P = 0.10). There were no significant differences in the adverse event rate between the CCM and control groups. Conclusions These preliminary results suggest that CCM exerts favourable effects on exercise tolerance and quality of life in patients with LVEF in the range of 40–45% with an acceptable safety profile. Further randomized controlled studies are planned to prove these effects.

A year in heart failure: an update of recent findings

“…Cardiac contractility modulation (CCM) consists of biphasic high‐voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period and has been shown to improve intramyocardial calcium handling. CCM has improved symptoms, exercise tolerance, and QOL and reduced the rate of HF hospitalizations in patients with ejection fractions between 25% and 45% 166–169 …”

“…CCM has improved symptoms, exercise tolerance, and QOL and re-duced the rate of HF hospitalizations in patients with ejection fractions between 25% and 45%. [166][167][168][169]…”

Breakthroughs in the treatment of heart failure with mildly reduced and preserved ejection fraction

“…Cardiac contractility modulation (CCM) therapy is a novel device that has been shown to improve cardiac function, exercise tolerance, and quality of life in HFrEF by applying a nonexcitatory stimulus during the absolute refractory period in the right interventricular septum in patients with HFrEF 53 . Exploratory analysis from randomized controlled trials has concluded that the efficacy of CCM therapy is higher in LVEF 35%–45% compared to patients with LVEF 25%–34% indicating its benefit in HFmrEF 54 . Experimental studies have found increased phosphorylation and subsequent activation of titin, a major protein in myocytes responsible for diastolic recoil, on serial endomyocardial biopsies within 3 months of CCM therapy in HFpEF 55 .…”

“…53 Exploratory analysis from randomized controlled trials has concluded that the efficacy of CCM therapy is higher in LVEF 35%-45% compared to patients with LVEF 25%-34% indicating its benefit in HFmrEF. 54 Experimental studies have found increased phosphorylation and subsequent activation of titin, a major protein in myocytes responsible for diastolic recoil, on serial endomyocardial biopsies within 3 months of CCM therapy in HFpEF. 55 A focused trial is yet to be performed in HFpEF and HFmrEF to examine the efficacy of CCM therapy in improving clinical outcomes.…”

Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway

“…Cardiac contractility modulation (CCM) is an electrical modality for the treatment of HF, that delivers relatively high voltage and long duration biphasic electrical impulses to the myocardium during the absolute refractory period; therefore, it neither influences the heart rhythm nor the normal propagation of the cardiac action potential across the valves [ 9 , 10 ]. CCM has been shown to increase the ventricular contractility with resultant improvement in the functional capacity of the heart, without the need for an additional oxygen request [ 11 ].…”