Cardiac resynchronization therapy (CRT) with biventricular pacing is an integral part of heart failure therapy in patients with reduced ejection fraction and wide QRS. Previous studies have demonstrated improved quality of life, reduced heart failure hospitalization, and decreased all-cause mortality. However, approx. 30% of patients still do not benefit from this therapy. High pacing thresholds and phrenic nerve stimulation are also common problems with BiV stimulation. Newer CRT systems with improved programmability and algorithms in conjunction with quadripolar left ventricular leads have solved some challenges of BiV pacing. However, BiV stimulation with non-physiological epicardial activation has shown a possible pro-arrhythmic effect which is more pronounced in the non-responder population.

On the other hand, CSP provides synchronous physiological ventricular activation with possible superior electrical and mechanical resynchronization compared to BiV pacing. Electrical activation maps obtained during CSP showed normalization of left bundle branch block with more homogeneous electrical resynchronization than in biventricular pacing. Additionally, BiV CRT effectively corrects mechanical dyssnchrony, demonstrated with homogenization of myocardial work. This has already been proven as the underlying pathophysiological mechanism for successful CRT response. However, the effect of CSP on echocardiographic parameters of mechanical dyssynchrony is not known.

Previous studies of CSP focused on feasibility and its benefits over right ventricular pacing in patients with refractory atrial fibrillation who underwent atrioventricular node ablation and pacemaker implantation. Promising results were followed by the acknowledgment of this physiological mode of pacing by the recent guidelines of European Society of Cardiology. However, studies evaluating the value of CSP as an alternative approach to BiV CRT in heart failure patients are limited. The purpose of this study is to compare the effects of CSP and conventional BiV pacing on electrocardiographic and echocardiographic parameters as well as on clinical outcomes in patients with heart failure with reduced ejection fraction (LVEF ≤35%), sinus rhythm, and left bundle branch block. In this single-center study, 60 patients will be randomized into one of two arms: a BiV pacing arm with BiV CRT implantation based on clinical guidelines or an experimental CSP arm with the implantation of a CSP device. Device with a defibrillator (ICD) will be selected at the discretion of the implanting physician. Baseline and follow up assessments will include clinical evaluation (New York Heart Association class, 6-minute walking distance), evaluation of quality of life (EQ-5D index), laboratory tests (N-terminal pro-B-type natriuretic peptide), electrocardiographic recordings (standard 12-leads ECG and high-resolution-ECG), and echocardiographic evaluation (standard echocardiographic parameters of LV reverse remodeling and non-invasive myocardial work assessment). Intra-operative and procedural parameters will also be recorded.

Investigators hypothesize that CSP could represent a feasible and safe alternative to conventional BiV pacing in terms of clinical, electrocardiographic, and echocardiographic outcomes.