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 the 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 device for cardiac resynchronization therapy 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. Cardiac conduction system pacing is currently a promising technique for these patients. Particularly, His bundle pacing (HBP) has been developed to achieve the same results. According to other studies HBP has shown greater improvement in hemodynamic parameters comparing with conventional biventricular CRT. But, nevertheless, there are significant clinical troubles with HBP, especially high pacing threshold. In this regard, in 2017, the left bundle branch pacing (LBBP) was developed, which demonstrated clinical advantages compared to conventional biventricular CRT. Also, since 2019, left bundle branch pacing-optimized CRT (LBBPO CRT) has been used in clinical practice. These methods have become an alternative to HBP due to the stimulation of LBB outside the blocking site, a stable pacing threshold and a narrow QRS complex duration on electrocardiogram. A series of case reports and observational studies have demonstrated the efficacy and safety of LBBP and LBBPO CRT in patients with CRT indications. However, it is not enough data about impact of CRT with LBBP and combined CRT with LBBP and LV pacing on myocardial remodeling, reducing mortality and complications. According to our hypothesis, CRT with LBBP and combined CRT with LBBP and LV pacing compared with conventional biventricular pacing will significantly improve the clinical outcomes and reverse myocardial remodeling in patients who are non-responders to biventricular CRT with HF, reduced LV ejection fraction and with indications to CRT devices with defibrillator function (CRT-D) or one of the CRT-D leads replacement.
The patient is willing and able to comply with the protocol and has provided written informed consent;
Male or female patients aged 18 to 80 years;
Patients with ischemic or non-ischemic cardiomyopathy;
Symptomatic HF for at least 3 months prior to enrollment in the study;
Coronary artery (CA) bypass grafting, balloon dilatation or CA stenting within 3 months prior to enrollment;
Acute myocardial infarction within 3 months prior to enrollment;
Acute coronary syndrome;
Patients with planned cardiovascular intervention (CA bypass grafting, balloon dilatation or CA stenting);
Parallel
Cardiac Resynchronization Therapy Devices with Defibrillator Function (CRT-D) or CRT-D Leads Replacement
DeviceThe local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The new CRT-D will be connected with leads and placed back into the pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture.
CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right and Left Ventricular Pacing
DeviceThe local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The lead implantation to the left bundle branch (LBB) will be performed by transvenous approach and special delivery system. The new CRT-D will be connected with the leads (LBB pacing lead will be connected to defibrillation lead (DL) IS-1 connector of CRT-D and IS-1 tip of DL will be capped) and placed back into pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture. RV and LV pacing will be inactivated and only LBB pacing will be switched on.
CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right Ventricular Pacing
DeviceThe local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The lead implantation to the left bundle branch (LBB) will be performed by transvenous approach and special delivery system. The new CRT-D will be connected with the leads (LBB pacing lead will be connected to defibrillation lead (DL) IS-1 connector of CRT-D and IS-1 tip of DL will be capped) and placed back into pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture. LBB and LV pacing will be switched on.
All-cause mortality or worsening of heart failure requiring unplanned hospitalization (%)
Definition of all-cause mortality All deaths and all heart transplants due to the terminal heart failure. Heart transplanted patients will be dropped out and followed in respect of their vital status for the duration of the study. Definition of worsening of heart failure requiring unplanned hospitalization Patients requiring intra-venous medication for heart failure (including diuretics, vasodilators or inotropic agents) or a substantial increase in oral diuretic therapy for heart failure (i. e. an increase of Furosemide ≥ 40 mg or equivalent, or the addition of a thiazide to a loop diuretic) will be deemed to have worsening of heart failure. Further, rales and/or S3 sound, chest x-ray, worsening of dyspnoea, worsening of peripheral edema and increase of class NYHA will be assessed for determination of worsening of heart failure. Unplanned hospitalization is defined as any in-hospital stay over one date change, and not planned by the Investigator
All-cause Mortality (%)
As defined for primary endpoint: all deaths and all heart transplants because of terminal heart failure.
Cardiovascular Mortality (%)
All deaths due to cardiovascular reasons and all heart transplants because of terminal HF. Deaths due to worsening of HF, acute coronary syndrome, cerebrovascular accidents, or other cardiovascular events will qualify for this secondary endpoint.
Worsening of Heart Failure Requiring Unplanned Hospitalization (%)
As defined for the primary end-point: patients requiring intra-venous medication for HF (including diuretics, vasodilators, or inotropic agents) or a substantial increase in oral diuretic therapy for HF (i. e. an increase of Furosemide ≥ 40 mg or equivalent, or the addition of a thiazide to a loop diuretic) will be deemed to have worsening of HF. Further, rales and/or S3 sound, chest x-ray, worsening of dyspnoea, worsening of peripheral edema, and increase of class NYHA will be assessed for determination of worsening of HF. Unplanned hospitalization is defined as any in-hospital stay over one date change, and not planned by the Investigator. Reasons for worsening of HF may include atrial fibrillation, acute coronary syndrome and hypertension.
Unplanned Hospitalization due to Cardiovascular Reason (%)
Any in-hospital stay over one date change due to cardiovascular reason, which includes worsening of HF, acute coronary syndrome, cerebrovascular accidents, or other cardiovascular events, and not planned by the Investigator. In case the hospitalization is classified as planned by the Investigator, and the time interval between the decision to hospitalize and the hospitalization is less than 24 hours.
Echocardiography Left Ventricular Volume Improvement (%)
Echocardiographic measurements will be done at baseline, 6, 12, 18 and 24 month follow-up, to evaluate effect of CRT-D implantation on left ventricle (LV) volume. Improvements due to reverse remodelling of the heart will be evaluated by measuring left ventricular end-systolic volume (LVESV), which is supposed to decrease at follow-up. Further, LV volume improvement will be calculated using formula: ((A-B)/A) x 100% (A-baseline LVESV; B-follow-up LVESV).
Echocardiography Left Ventricular Ejection Fraction Improvement (%)
Echocardiographic measurements will be done at baseline, 6, 12, 18 and 24 month follow-up, to evaluate effect of CRT-D implantation on left ventricle (LV) contractility function. Improvements due to reverse remodelling of the heart will be evaluated by measuring left ventricular ejection fraction (LVEF), which is supposed to increase at follow-up. Further, LV contractility function improvement will be calculated using formula: ((A-B)/A) x 100% (A-baseline LVEF; B-follow-up LVEF).
NYHA Class
The NYHA functional classification provides a simple way of classifying the extent of HF. It is based on questions, related to the usual daily activities and symptoms posed to the patients, and it will be determined at enrollment, baseline and at each follow-up visit. In ablated patients an improvement of NYHA class is expected, the analysis of which will help to assess the efficacy of ablation therapy.
Rate of Drug Support Requirements (%)
Beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, diuretics, and sodium-glucose transporter type 2 inhibitors, antiarrhythmics and diuretics are drugs commonly taken by patients suffering from HF. Those drugs may have the potential to induce arrhythmic events. In patients with left bundle branch pacing (LBBP) CRT-D a reduction in drug consumption is expected, with a consequent reduction of side effects. The evaluation of the drug regimen will help to assess the effectiveness of LBBP.
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