Cardiac contractility modulation improves HFrEF outcomes
BOSTON — In patients with HF with reduced ejection fraction, cardiac contractility modulation improved exercise tolerance and quality of life and reduced hospitalizations for HF, according to findings presented at the Heart Rhythm Society Annual Scientific Sessions.
A previous subgroup analysis of the FIX-HF-5 trial of the cardiac contractility modulation therapy (Optimizer, Impulse Dynamics) showed the device improved exercise tolerance and quality of life in patients with HF and ejection fraction between 25% and 45%. The current FIX-HF-5C study was undertaken to confirm those findings, William T. Abraham, MD, FACC, FACP, professor of internal medicine and chief of the division of cardiology at The Ohio State University Wexner Medical Center, said during a presentation.
The researchers randomly assigned 160 patients with NYHA class III or IV HF, QRS duration < 130 ms and EF between 25% and 45% to receive cardiac contractility modulation or continued medical therapy for 24 weeks.
“These patients aren’t yet sick enough ... to be considered a transplant candidate” or eligible for a left ventricular assist device, Abraham said during a press conference. “On the other hand, they are not doing well enough for them or their clinician to be satisfied with how they are doing. There aren’t other options available to improve their quality of life, their functional capacity or their exercise capacity.”
The primary outcome was peak VO2. Other outcomes of interest included Minnesota Living With Heart Failure questionnaire score, NYHA functional class and 6-minute walk distance. The key safety outcome was freedom from device-related adverse events, with a prespecified lower bound of 70%.
The researchers used Bayesian repeated measures linear modeling for analysis of the primary endpoint, including 30% borrowing from the FIX-HF-5 subgroup. The combined cardiac contractility modulation cohort was 76% men with a mean age of 61 years, and the combined control cohort was 71% men with a mean age of 60 years.
At 24 weeks, peak VO2 was 15.042 ml O2/kg/min in the cardiac contractility modulation group and 14.206 ml O2/kg/min in the control group (mean difference, 0.84 ml O2/kg/min; 95% Bayesian credible interval, 0.123-1.552), according to the researchers. The probability that cardiac contractility modulation is superior to control was 0.989, exceeding the criterion for statistical significance of 0.975.
In addition, at 24 weeks, compared with the control group, the treatment group had better Minnesota Living With Heart Failure questionnaire score (mean difference, –11.7; 95% CI, –17.6 to –5.9; P < .001), had more patients improve in NYHA class (81% vs. 41%; P < .001) and had better performance on the 6-minute walk test (P = .02).
Seven device-related events occurred, for a lower bound of 79.9% freedom from device-related events, exceeding the primary safety endpoint goal, Abraham said.
CV death or HF hospitalization was 10.2% in the control group vs. 2.9% in the treatment group (P = .048), according to the researchers.
“These studies establish [cardiac contractility modulation] as a new addition to our armamentarium for the treatment of NYHA Class III and ambulatory Class IV patients with narrow QRS complexes,” Abraham said.
The device is not yet approved for general commercial use in the United States, but the FDA has granted it priority review and accepted it into the Expedited Access Pathway program, according to Abraham.
The FIX-HF-5C results were simultaneously published in JACC: Heart Failure. – by Erik Swain
Abraham WT, et al. LBCT01-02. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 9-12, 2018; Boston.
Disclosure: The study was supported by research grants from Impulse Dynamics. Abraham reports he served as a consultant for Impulse Dynamics.