Heart failure (HF) is the most common nosology encountered in clinical practice. Its incidence and prevalence increase exponentially with increasing age and it is associated with increased mortality, more frequent hospitalization and decreased quality of life. An initial approach to the treatment of HF patients with reduced left ventricular (LV) systolic function and left bundle branch block (LBBB) was implantation of cardioresynchronization device using biventricular pacing. This has resulted in long-term clinical benefits such as improved quality of life, increased functional capacity, reduced HF hospitalizations and overall mortality. However, conventional cardiac resynchronization therapy (CRT) is effective in only 70% of patients. And the remaining 30% of patients are non-responders to conventional CRT. Subsequently, His bundle pacing (HBP) has been developed to achieve the same results. According to other studies HBP has showed greater improvement in hemodynamic parameters than with conventional biventricular CRT. But, nevertheless, there are significant clinical troubles with HBP. In this regard, in 2017, the left bundle branch pacing (LBBP) was developed, which demonstrated clinical advantages compared to biventricular CRT. This method has become an alternative to HBP due to the stimulation of LBB outside the blocking site, a stable pacing threshold and a narrow QRS duration. A series of case reports and observational studies have demonstrated the efficacy and safety of LBBP in patients with CRT indications. However, it is not enough data about CRT with LBBP effectiveness in LV remodeling, reducing mortality and complications. According to our hypothesis, CRT with LBBP compared with conventional biventricular CRT will significantly improve the clinical outcomes and reverse LV remodeling in patients with chronic HF with reduced LV ejection fraction and reduce the number of non-responders to conventional CRT.

The heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of more than 37.7 million individuals globally. In the developed world, this disease affects approximately 2.0% of the adult population. In the United States the total percentage of the population with HF is projected to rise from 2.4% in 2012 to 3.0% in 2030. In Russian Federation the prevalence of chronic HF (CHF) is 10.2%. The main cause of CHF is a coronary heart disease, which accounts for about 70.0%, and the remaining 30.0% are non-ischemic heart diseases. More than 2 decades of research has established the role of cardiac resynchronization therapy (CRT) in medically refractory, mild to severe systolic HF with abnormal QRS duration and morphology. The prolongation of QRS (120 ms or more) occurs in 14.0% to 47.0% of HF patients and the ventricular conduction disturbance, most commonly left bundle branch block (LBBB), is present in approximately one-third of HF, leading to mechanical dyssynchrony of ventricles. Prospective randomized studies of patients with both ischemic HF (IHF) and non-ischemic HF (NIHF) have shown that CRT translates into long-term clinical benefits, such as improved quality of life, increased functional capacity, reduction in hospitalization for HF, and overall mortality. These patients qualified as responders to CRT. However, CRT is effective in 70.0% of patients, and the remaining 30.0% do not respond to the device therapy. In fact, biventricular CRT leads to the fusion of two fronts of non-physiological excitation waves and leaves a significant residual dyssynchrony.

His bundle pacing (HBP) is possible alternative to biventricular CRT. During HBP there is a physiological electromechanical synchrony by facilitating conduction through the native His-Purkinje system. HBP promotes higher electrical ventricular resynchronization than biventricular CRT. Studies have shown that HBP, as well as conventional biventricular CRT, improves cardiac function, which leads to a decrease in the number of HF hospitalizations. The main unsolved problems that limit the use of HBP are the low amplitude of the intracardiac signal, high pacing thresholds and troubles associated with lead implantation in the area of the His bundle, which ultimately increases the risk of re-implantation.

In 2017, W. Huang et al. pioneered left bundle branch pacing (LBBP) and demonstrated that it provided clinical benefits in patients with HF and LBBB, aiming to pacing 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 the LBB capture. LBBP has emerged as an alternative to HBP due to pacing of LBB outside the blocking site, a stable pacing threshold, and a narrow QRS in patients with bradycardia. In clinical cases of W. Huang et al. was demonstrated for the first time that LBBP could lead to complete correction of LBBB and improvement in cardiac function in patients with LBBB and HF. In another observational study, W. Zhang et al. showed 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.

The above studies demonstrate that LBBP is clinically feasible in patients with HF and LBBB. However, there are still few data about CRT using LBBP in patients with HF and reduced LVEF. There are also few studies on direct comparison of changes in clinical, speckle tracking echocardiography and other laboratory and instrumental parameters between patients with conventional biventricular CRT and CRT using LBBP.

CRT induces reverse remodeling of the affected heart, improves LV systolic and diastolic function and left heart filling pressure. The measurement of fibrosis and remodeling biomarkers representing the pattern of active processes in HF be useful.

The relationship between changes in the biomarkers level and reverse remodeling process in patients with LBBP is currently poorly understood. And there are no publications regarding the correlation of the level of such biomarkers as MR-proANP, GDF-15, galectin-3, ST2, MR-proADM and PINP with clinical and instrumental indicators of patients with LBBP in the available literature. This creates all the prerequisites for studying the association of the above biomarkers with the reverse remodeling process in patients with CRT using LBBP.

Inclusion criteria:

1. The patient is willing and able to comply with the protocol and has provided written informed consent;
2. Male or female patients aged 18 to 80 years;
3. Patients with ischemic or non-ischemic cardiomyopathy;
4. Symptomatic HF for at least 3 months prior to enrollment in the study;
5. New York Heart Association (NYHA) functional class HF ≥ II;
6. Patients with HF in sinus rhythm (SR) with LVEF ≤ 35% (measured in the last 6 weeks prior to enrollment), QRS duration ≥150 ms with LBBB morphology;
7. Patients with HF in SR with LVEF ≤ 35% (measured in the last 6 weeks prior to enrollment), QRS duration 130-149 ms with LBBB morphology;
8. Patients with HF in SR with LVEF ≤ 35% (measured in the last 6 weeks prior to enrollment), QRS duration ≥150 ms with non-LBBB morphology;
9. Patients with symptomatic persistent or permanent atrial fibrillation, HF with LVEF < 40% (measured in the last 6 weeks prior to enrollment) and an uncontrolled heart rate who are candidates for atrioventricular junction ablation (irrespective of QRS duration);
10. Patients with HF, LVEF < 40% (measured in the last 6 weeks prior to enrollment) and indications for continuous ventricular pacing due to bradycardia;
11. Patients who have received a conventional pacemaker or an implanted cardioverter-defibrillator and who subsequently develop symptomatic HF with LVEF < 40% (measured in the last 6 weeks prior to enrollment) despite optimal medical therapy, and who have a significant proportion of right ventricle pacing;
12. Optimal HF medical therapy.

Exclusion criteria:

1. Coronary artery (CA) bypass grafting, balloon dilatation or CA stenting within 3 months prior to enrollment;
2. Acute myocardial infarction within 3 months prior to enrollment;
3. Acute coronary syndrome;
4. Patients with planned cardiovascular intervention (CA bypass grafting, balloon dilatation or CA stenting);
5. Patients listed for heart transplant;
6. Patients with implanted cardiac assist device;
7. Acute myocarditis;
8. Infiltrative myocardial disease;
9. Hypertrophic cardiomyopathy;
10. Severe primary stenosis or regurgitation of the mitral, tricuspid and aortic valves;
11. Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertility age;
12. Mental or physical inability to participate in the study;
13. Patients unable or unwilling to cooperate within the study protocol;
14. Patients with rheumatic heart disease;
15. Mechanic tricuspid valve patients;
16. Patients with any serious medical condition that could interfere with this study;
17. Enrollment in another investigational drug or device study;
18. Patients not available for follow-up;
19. Patients with severe chronic kidney disease (estimated glomerular filtration rate ˂ 30 ml/min/1.73 m2);
20. Life expectancy ≤ 12 months;
21. Participation in another telemonitoring concept.