HOPE for a better selection of patients for cardiac contractility modulation.

Cardiac contractility modulation (CCM) is an innovative devicebased therapy for the treatment of patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and reduced ejection fraction (HFrEF) with a narrow QRS complex (and therefore with no indication for cardiac resynchronization therapy). The CCM therapy is based on the delivery, by an impulse pocket generator (Optimizer Smart®), of high-voltage (≈7.5 V) and long-duration (≈20 ms) biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium [1]. Therefore, these signals do not cause a novel myocardial contraction, but induce an improvement in calcium handling and, consequently, an increase in myocardial contractility [2]. Besides improving calcium handling, CCM therapy induces several positive effects (Table 1) that affects the entire biology of the failing myocardium [3–5]. In randomized controlled trials, CCM therapy improves functional capacity (i.e. VO2 peak at cardiopulmonary exercise test) [6]; also, in a real-world registry, CCM therapy is associated with a lower rate of HF-related hospitalizations [7]. In addition, CCM therapy induces both left and right ventricular reverse remodeling [8–10]. Based on the results of these randomized clinical trials, the Optimizer Smart® system has been approved in countries covered by CE markings since October 2016 and granted United States Food and Drug Administration (FDA) approval in March 2019. As with all device-based therapies for HF, appropriate patient selection is crucial for increasing the possibility of clinical and echocardiographic response. Because no practical guidance on proper patient selection for CCM therapy is currently provided by the European Society of Cardiology and the American College of Cardiology/American Heart Association guidelines [11,12], we proposed the HOPE algorithm as a simple tool for screening and selecting outpatients with HFrEF/HFmrEF in which CCM therapy is more likely to be effective (Figure 1).