Should HFrEF patients with NYHA class II expect benefit from CCM therapy? Results from the MAINTAINED observational...

Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with refractory systolic heart failure and normal QRS width. Randomized trials demonstrated benefits of CCM primarily for patients with severe heart failure (> NYHA class II).

To better understand individualized indication in clinical practice, we compared the effect of CCM in patients with baseline NYHA class II vs. NYHA class III or ambulatory IV over the 5-year period in our large clinical registry (MAINTAINED Observational Study).

Changes in NYHA class, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), NT-proBNP level, and KDIGO chronic kidney disease stage were compared as functional parameters. In addition, mortality within 3 years was compared with the prediction of the Meta-Analysis Global Group in Chronic heart failure risk score.

A total of 172 patients were included in the analyses (10% with NYHA class II). Only patients with NYHA class III/IV showed a significant improvement in NYHA class over 5 years of CCM (II: 0.1 ± 0.6; p = 0.96 vs. III/IV: - 0.6 ± 0.6; p < 0.0001). In both groups, LVEF improved significantly (II: 4.7 ± 8.3; p = 0.0072 vs. III/IV: 7.0 ± 10.7%; p < 0.0001), while TAPSE improved significantly only in NYHA class III/IV patients (II: 2.2 ± 1.6; p = 0.20 vs. III/IV: 1.8 ± 5.2 mm; p = 0.0397). LVEF improvement was comparable in both groups over 5 years of CCM (p = 0.83). NYHA class II patients had significantly lower NT-proBNP levels at baseline (858 [175/6887] vs. 2632 [17/28830] ng/L; p = 0.0044), which was offset under therapy (399 [323/1497] vs. 901 [13/18155] ng/L; p = 0.61). Actual 3-year mortality was 17 and 26% vs. a predicted mortality of 31 and 42%, respectively (p = 0.0038 for NYHA class III/IV patients).

NYHA class III/IV patients experienced more direct and extensive functional improvements with CCM and a survival benefit compared with the predicted risk. However, our data suggest that NYHA class II patients may also benefit from the sustained positive effects of LVEF improvement.