Left Bundle Branch Pacing on Outcomes and Ventricular Remodeling in Biventricular CRT Nonresponders

NCT05760924 | Recruiting

• 1 other identifier: RESCUE
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure; Left Bundle-Branch Block; Ischemic Cardiomyopathy; Non-ischemic Dilated Cardiomyopathy; Left Ventricular Dysfunction; Left Ventricle Remodeling

Keywords

Cardiac Resynchronization Therapy; Biventricular Pacing; Left Bundle Branch Pacing; Speckle Tracking Echocardiography; Biomarker of Fibrosis and Remodeling; Combined Left Bundle Branch and Left Ventricular Pacing; CRT Non-responder; CRT Responder

Outcome Measures

Primary Outcomes (1)

• 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

  24 month

Secondary Outcomes (14)

• All-cause Mortality (%)

  24 month

• Cardiovascular Mortality (%)

  24 month

• Worsening of Heart Failure Requiring Unplanned Hospitalization (%)

  24 month

• Unplanned Hospitalization due to Cardiovascular Reason (%)

  24 month

• All-cause Hospitalization (%)

  24 month

Other Outcomes (4)

• Echocardiography Left Ventricular Volume Improvement (%)

  24 month

• Echocardiography Left Ventricular Ejection Fraction Improvement (%)

  24 month

• NYHA Class

  24 months]

Study Arms (3)

Cardiac Resynchronization Therapy with Biventricular Pacing

ACTIVE COMPARATOR

Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement will be performed in this group of patients.

Device: Cardiac Resynchronization Therapy Devices with Defibrillator Function (CRT-D) or CRT-D Leads Replacement

Cardiac Resynchronization Therapy with Left Bundle Branch Pacing

EXPERIMENTAL

Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement with the new lead implantation to the left bundle branch and inactivation of conventional right and left ventricular pacing will be performed in this group of patients.

Device: CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right and Left Ventricular Pacing

Cardiac Resynchronization Therapy with Combined Left Bundle Branch and Left Ventricular Pacing

EXPERIMENTAL

Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement with the new lead implantation to the left bundle branch and inactivation of conventional right ventricular pacing will be performed in this group of patients.

Device: CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right Ventricular Pacing

Interventions

Cardiac Resynchronization Therapy Devices with Defibrillator Function (CRT-D) or CRT-D Leads Replacement DEVICE

The 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.

Cardiac Resynchronization Therapy with Biventricular Pacing

CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right and Left Ventricular Pacing DEVICE

The 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.

Cardiac Resynchronization Therapy with Left Bundle Branch Pacing

CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right Ventricular Pacing DEVICE

The 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.

Cardiac Resynchronization Therapy with Combined Left Bundle Branch and Left Ventricular Pacing

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• New York Heart Association (NYHA) functional class HF ≥ II;
• Patients who are non-responders to biventricular CRT with HF, reduced LVEF and CRT-D replacement or one of the CRT-D leads replacement indications (without LVEF increase ≥ 5% and/or without a left ventricle end-systolic volume decrease ≥ 15% after CRT-D implantation at least 1 year old);
• Optimal HF medical therapy.

You may not qualify if:

• 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);
• Patients listed for heart transplant;
• Patients with implanted cardiac assist device;
• Acute myocarditis;
• Infiltrative myocardial disease;
• Hypertrophic cardiomyopathy;
• Severe primary stenosis or regurgitation of the mitral, tricuspid and aortic valves;
• Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertility age;
• Mental or physical inability to participate in the study;
• Patients unable or unwilling to cooperate within the study protocol;
• Patients with rheumatic heart disease;
• Mechanic tricuspid valve patients;

Sponsors & Collaborators

• Tomsk National Research Medical Center of the Russian Academy of Sciences: lead

Study Sites (1)

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Tomsk, Russia

RECRUITING

MeSH Terms

Conditions

Heart Failure; Bundle-Branch Block; Ventricular Dysfunction, Left; Ventricular Remodeling

Interventions

Cardiac Resynchronization Therapy Devices

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Heart Block; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ventricular Dysfunction; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Pacemaker, Artificial; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies

Study Officials

• Tariel A Atabekov, Ph.D.

  Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

  PRINCIPAL INVESTIGATOR

• Roman E Batalov, M.D.

  Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

  STUDY DIRECTOR

Central Study Contacts

Tariel A Atabekov, Ph.D.

CONTACT

+79528002625; kgma1011@mail.ru

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 9, 2023
• Study Start: November 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR, ANALYTIC CODE
• Time Frame: Starting 12 months after publication
• Access Criteria: Principal investigator and study director will review requests and criteria for reviewing requests

Locations

RU (1)