Electrical heart failure treatment in the Goldilocks zone: cardiac contractility modulation proves equally effective for heart failure control in HFrEF patients with mid-range QRS durations

Abstract Background Current guidelines recommend a four pillar therapy for heart failure with reduced ejection fraction (HFrEF). A subgroup of patients, namely those with a QRS duration (QRSd) ≥150 ms, may also qualify for cardiac resynchronization therapy. However, a 30% CRT non-responder rate persists, with patients with narrower QRSd (i.e., QRSd <150 ms) and non-left bundle branch block receiving less benefit. At present, cardiac contractility modulation (CCM) has only been established in patients with QRSd <120 ms. Given these limitations, new options for additional device therapy are urgently sought for those patients who face drug-refractory HFrEF and with intermediate QRSd of 120-149 ms. Purpose Primarily to evaluate the impact of CCM on HF-related hospitalizations and secondarily on left ventricular EF (LVEF) as well as quality of life (by Minnesota Living with Heart Failure Questionnaire (MLWHF) score and New York Heart Association (NYHA) class) in a real-world population of HFrEF patients with QRSd 120-149 ms, compared to QRSd <120 ms. Methods CCM-REG enrolled 503 HF patients receiving CCM with a follow-up of up to 2 yrs. HF-related hospitalization rates were available for 1 yr pre-implant. Safety was assessed by comparison of actual versus MAGGIC score predicted mortality. Results 455 patients were studied for these analyses. Among 111 subjects with QRSd 120-149 ms (mean QRSd 130±8 ms, age 68±10 yrs, 20% female, LVEF 29±9%, 82% NYHA class III), CCM diminished HF-related hospitalization rate by 72% (pre- vs. post-implant 0.90 vs. 0.25 events/per patient-yr over 2 yrs; p<0.001; Figure). LVEF improved by 7±8% (p=0.01 vs. baseline), MLWHFQ score by 10±23 pts (p=0.01 vs. baseline), and NYHA class by 0.5±0.7 classes (<0.001 vs. baseline). The effect size was similar to that in the QRSd <120 ms patients. Mortality within first year was 19% in QRSd 120-149 ms patients and thus not significantly different from the MAGGIC score prediction. Conclusions CCM significantly improved HF control in symptomatic HFrEF patients with moderately prolonged QRSd 120-149 ms. The effect was similar to patients with QRSd <120ms.Reduction in hospitalization rates