Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients With Advanced Heart Failure - FIX-HF-5 — Presented at ACC.09/i2

Description:

The goal of the trial was to evaluate cardiac contractility modulation plus optimal medical therapy compared with optimal medical therapy alone in patients with advanced heart failure. Cardiac contractility modulation is nonexcitatory electrical signals delivered during the refractory period with the aim to improve contractility.

Hypothesis:

Cardiac contractility modulation will be more effective at improving certain parameters of metabolism and will be noninferior with safety endpoints.

Study Design

Study Design:

Patients Screened: 774
Patients Enrolled: 428
Mean Follow Up: 12 months
Mean Patient Age: 56 years

Patient Populations:

  • Patients with NYHA III or IV, left ventricular ejection fraction ≤35%, and narrow QRS

Primary Endpoints:

  • Primary safety endpoint defined as all-cause mortality and all-cause hospitalization
  • Primary efficacy endpoint defined by anaerobic threshold

Secondary Endpoints:

  • Peak VO2
  • Quality of life

Drug/Procedures Used:

Patients with New York Heart Association (NYHA) III or IV heart failure and narrow QRS were randomized to cardiac contractility modulation plus optimal medical therapy (n = 215) versus optimal medical therapy alone (n = 213).

Concomitant Medications:

At baseline, the use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was 91%, a beta-blocker was 94%, and an aldosterone inhibitor was 44%.

Principal Findings:

Overall, 428 patients were randomized. The mean age was 58 years, 27% were women, 65% were ischemic, 91% were NYHA class III, left ventricular ejection fraction was 26%, QRS duration was 102 msec, and peak VO2 was 14.7 ml/kg/min.

The incidence of the primary efficacy endpoint, anaerobic threshold responder analysis (among completers), was 17.6% with treatment versus 11.7% with control (p = 0.093). Peak VO2 improved by 0.65 ml/kg/min (p = 0.024) and quality of life improved by -9.7 points (p < 0.0001) by cardiac contractility modulation compared with optimal medical therapy alone. The incidence of the primary safety outcome by 50 weeks was 52% with cardiac contractility modulation versus 48% with optimal medical therapy alone (p for noninferiority = 0.03).

Findings were more pronounced by cardiac contractility modulation among patients with NYHA class III and ejection fraction ≥25%.

Interpretation:

Among patients with advanced heart failure (NYHA class III or IV), low left ventricular ejection fraction (≤35%), and narrow QRS, the use of cardiac contractility modulation failed to improve the primary efficacy outcome, anerobic threshold; however, this therapy was effective at improving peak VO2 and quality of life. Safety outcomes were noninferior in the experimental group compared with optimal medical therapy alone. Anaerobic threshold was improved in subgroup analysis (NYHA class III and ejection fraction ≥25%), where VO2 and quality of life were also more pronounced and sustained through 12 months.

References:

Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients With Advanced Heart Failure (FIX-HF-5). Presented by Dr. William Abraham at ACC.09/i2, Orlando, FL, March 2009.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, Acute Heart Failure

Keywords: Ventricular Function, Left, Cardiac Pacing, Artificial, Quality of Life, Anaerobic Threshold, Heart Failure, Stroke Volume


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