Credit: V. Summersby/Macmillan Publishers Limited

Cardiac contractility modulation (CCM) is safe, improves exercise tolerance and quality of life, and reduces hospitalizations related to heart failure (HF) in patients in NYHA class III–IV and with an ejection fraction (EF) of 25–45%. These findings from the FIX-HF-5C trial, presented at the Heart Rhythm Society Scientific Sessions 2018, confirm previous results from a subgroup analysis of the FIX-HF-5 trial.

CCM therapy is the application of nonexcitatory electrical signals to the heart during the absolute refractory period of the action potential, to augment cardiac muscular contraction without increasing myocardial oxygen consumption. This therapy was developed for the treatment of symptomatic patients with reduced or midrange EF who are not candidates for cardiac resynchronization therapy. In the FIX-HF-5 trial, CCM treatment effects in primary and secondary end points reached significance only in an exploratory subgroup analysis in patients with an EF of 25–45%. Thus, the FIX-HF-5C trial was designed to confirm the safety and efficacy of CCM in this group of patients identified as best responders to therapy. A total of 160 patients with NYHA class III or IV HF and an EF of 25–45% were randomly assigned to CCM plus medical therapy or to medical therapy alone. The investigators used a Bayesian statistical analysis to take advantage of data from the original study.

CCM therapy had a stronger effect in each efficacy parameter in patients with an EF of 35–45%

At 24 weeks, CCM therapy led to improvements in exercise tolerance compared with medical therapy alone, as shown by a difference in peak oxygen consumption of 0.84 ml O2/kg/min (95% Bayesian credible interval: 0.123–1.552 ml O2/kg/min) between the treatment groups. Quality of life (assessed using the Minnesota Living with Heart Failure Questionnaire), 6-min hall walking test, and NYHA class were also better in patients who received CCM therapy than in those receiving medical therapy alone. CCM therapy was safe, with 80% of patients free from device-related adverse events, and use of CCM reduced the composite of cardiovascular death and HF hospitalizations from 10.8% to 2.9%.

Interestingly, CCM therapy had a stronger effect in each efficacy parameter in patients with an EF of 35–45% than in those with an EF of 25–34%. Future studies with longer follow-up are needed to assess the long-term effects of CCM on mortality and hospitalizations.