Abstract 3558: Cardiac Contractility Modulation Improves Exercise Tolerance in NYHA Class III Patients With Narrow QRS and EF Between 25 and 35%: A Subgroup Analysis of the FIX-HF-5 Study
Background: Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered to the heart during the absolute ventricular refractory period intended to improve contraction. The safety and efficacy of CCM was tested in 428 NYHA III or IV heart failure patients with EF≤35% and narrow QRS randomized to optimal medical treatment (OMT) plus CCM versus OMT alone: the FIX-HF-5 study. In the overall population, CCM had no significant impact on anaerobic threshold (AT) but did significantly increase peak VO2 (pVO2). We sought to identify subgroups of patients who showed the most robust clinically significant response to CCM.
Methods and Results: Protocol specified multi-regression analysis was used to determine if baseline EF, NYHA, pVO2 or etiology of heart failure influenced the impact of CCM on AT, the study’s primary efficacy endpoint. Etiology and baseline pVO2 did not impact efficacy. However, baseline NYHA III and an EF≥25% appeared to be predictors of increased efficacy. When a post-hoc analysis was performed on the combined subgroup of NYHA III and an EF≥25% (97 OMT and 109 CCM patients, 48% of the entire population) AT increased by 0.10±2.36 in CCM vs −0.54±1.83 ml/kg/min in OMT (p=0.03) and pVO2 increased by 0.34±3.11 in CCM vs −0.97±2.31 (p=0.001) at 24 weeks compared to baseline. 59% of CCM vs 42% of OMT subjects showed a 10 point or greater reduction in Minnesota Living with Heart Failure Questionnaire (p=0.01). These differences were maintained at 50 weeks.
Conclusions: This retrospective analysis indicates that CCM significantly improves objective parameters of exercise tolerance in a subgroup of patients with normal QRS duration, NYHA class III symptoms and 25%≤EF≤35%. If confirmed in prospective studies, CCM can address a large, currently unserved population of patients living with marked limitation of exercise tolerance.