CCM in CHF: FIX-HF-5C Study
- 1. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation FIX-HF-5C Study
- 2. Introduction • Cardiac contractility modulation (CCM) is an electrical device-based approach developed for the treatment of CHF with reduced and midrange ejection fractions (EFs). • CCM signals are non-excitatory electrical signals applied during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction
- 4. William T. Abraham et al. JCHF 2018;j.jchf.2018.04.010 2018 The Authors
- 5. • CCM signals are delivered from an implanted pulse generator connected to the heart via one atrial lead (for p-wave sensing) and two ventricular leads (for sensing timing of local electrical activation and for delivering CCM signals). • CCM signal are biphasic pulses delivered during the absolute refractory period. • CCM signals impact the biology of the failing muscle local and, over time, distal to the site of signal delivery. • These myocardial effects ultimately contribute to favourable clinical effects
- 6. • The randomized FIX-HF-5 trial was performed to study the safety and efficacy of CCM in patients with NYHA class III or IV symptoms and reduced EF. • That 428-patient study met its primary safety endpoint (a noninferiority assessment of the composite of all-cause mortality and all-cause hospitalizations). • However, the primary efficacy endpoint, responders’ analysis of changes in ventilatory anaerobic threshold on cardiopulmonary exercise stress testing (CPX), was not met. • An exploratory, hypothesis-generating subgroup analysis showed significant treatment effects on primary and secondary endpoints in patients with EFs ranging from 25% to 45% • Authors therefore designed the FIX-HF-5 confirmatory study (FIX- HF-5C study) to prospectively test the efficacy and safety of CCM in patients with EF ranging from 25% to 45%.
- 7. METHODS • This was a prospective, randomized study of optimal medical therapy (OMT) alone (control group) versus OMT plus CCM (CCM treatment group) in patients with medically refractory, but ambulatory heart failure (NYHA functional class III or IV) with EF ranging from 25% to 45%.
- 8. Inclusion Criteria • New York Heart Association functional class III or IV heart failure • QRS duration < 130 ms • Ejection fraction between 25% and 45%
- 9. • Patients underwent baseline testing, which included : 1. peak oxygen consumption (pVO2) 2. determination of quality of life (QoL) score using the Minnesota Living with Heart Failure Questionnaire (MLWHFQ), 3. 6-min hall walk test (6MHW), 4. NYHA functional class assessment. • Follow-up visits were at weeks 12 and 24, at which time CPX, MLWHFQ, 6MHW, and NYHA functional class assessments were performed
- 10. • Primary Outcome: Peak VO2 • Secondary Outcome(s): 1. Minnesota Living with Heart Failure questionnaire score 2. NYHA 3. 6-minute walk distance test • Primary safety endpoint : was defined as the proportion of subjects who did not experience either an Optimizer device-related complication or a procedure-related complication by 24 weeks. • Follow-up: 24 weeks
- 13. RESULTS
- 17. CONCLUSION In patients with NYHA lll EF 25-45%, not indicated for CRT, CCM improves: • Peak VO2 • 6 Minute Walk • QoL (MLWHFQ) • NYHA Class • 6 –month rate of CV mortality and HF hospitalization Adverse event rate was no different than control.
Editor's Notes
- #5: Clinical Implementation of CCM Treatment CCM signals are delivered from an implanted pulse generator connected to the heart via one atrial lead (for p-wave sensing) and two ventricular leads (for sensing timing of local electrical activation and for delivering CCM signals). CCM signal are biphasic pulses delivered during the absolute refractory period. CCM signals impact the biology of the failing muscle local and, over time, distal to the site of signal delivery. These myocardial effects ultimately contribute to favorable clinical effects. CCM = cardiac contractility modulation; MLWHFQ = Minnesota Living With Heart Failure questionnaire; NYHA = New York Heart Association.