Randomized Trial of Left Bundle Branch Pacing Effect on Clinical Outcomes and Left Ventricular Remodeling in Patients With Nonresponse to Biventricular Cardiac Resynchronization Therapy

Recent advances in the cardiovascular pharmacological and cardiac device-based therapy have led to many benefits which improve the clinical condition, reduce morbidity, and increase survival in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) with biventricular pacing is a well-established method for the treatment of patients with the left bundle branch block (LBBB), cardiomyopathy of difference etiologies and HF with the reduced left ventricular ejection fraction (LVEF). Several prospective randomized trials have shown that biventricular CRT improves quality of life, improves exercise tolerance, reduces HF hospitalizations, and reduces all-cause mortality. The enthusiasm for this remarkable efficacy of CRT is limited by the fact that a proportion of patients have no benefits from this treatment. This category of patients is called nonresponder. These patients have no clinical and echocardiographic improvement with CRT. According to some studies, 30-50% of patients with biventricular CRT are non-responders.

The left bundle branch pacing (LBBP) was proposed in 2017 and demonstrated clinical benefits in patients with HF and LBBB, aiming to pace the proximal left bundle branch (LBB) along with LV myocardial capture. During selective pacing, only LBB is captured without the nearby myocardium, while with non-selective LBBP the septal myocardium is captured. LBBP with lead implanted slightly distal to the His bundle and screwed deep into the left ventricular (LV) septum is ideal for LBB capture. LBBP has emerged as an alternative to HBP due to pacing outside the blocking site, a stable pacing threshold, and a narrow QRS complex duration on electrocardiogram in patients with the bradycardia. In some clinical cases for the first time was demonstrated that LBBP could lead to complete correction of LBBB and improvement in cardiac function in patients with LBBB and HF. In another observational study it was shown that LBBP could be a new method of CRT. Subsequently, several case reports and observational studies have demonstrated the efficacy and safety of LBBP in patients with indications for CRT device implantation.

However, proximal LBBP is inherently limited in its ability to restore the physiological activation of LV lateral wall in patients with the conduction delay in the distal segment of LBB, Purkinje fibers or LV myocardium. Moreover, it is possible that in many patients with LBBP, only LV septal myocardial capture has been obtained, resulting in a small but potentially important non-physiological delay in LV lateral wall activation.

Conventional biventricular CRT based on right ventricular (RV) and LV pacing is also limited in its ability to fully restore physiological LV activation. Limitations of biventricular CRT may also include the potential desynchronizing effect of RV pacing , non-physiological epicardial LV pacing, latency and suboptimal position of LV lead (paraseptal or apical) due to anatomical features of the target vein, and the presence of LV myocardial scar. The inability of biventricular CRT to restore physiological activation may be expressed in QRS complex widening, rather than in its narrowing. That is observed in a third of patients with biventricular CRT and associated with a poor prognosis.

The combination of LBB and LV pacing may overcome some of the aforementioned limitations of both methods, providing a narrower QRS complex and more effective CRT, especially in difficult cases and in patients with more severe HF. Several studies have shown that combined CRT with LBB and LV pacing is feasible and safe and provides greater electrical resynchronization compared to biventricular CRT.