Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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The present study will recruit 40 symptomatic heart failure patients with left ventricular ejection fraction (LVEF) below 35% and complete left bundle branch block(QRSd≥130 ms). Each patient was randomized to either left bundle branch pacing(LBBP) or biventricular pacing(BivP) and was followed up for at least 6 months. The objective is to compare the effects of LBBP and BivP on cardiac resynchronization in the treatment of heart failure by measurable clinical parameters.

Detailed Description
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The traditional biventricular pacing (BivP) is an established treatment to corrected the cardiac dyssynchrony in heart failure patients with left bundle branch block(LBBB). It has been proved that BivP can improve clinical symptoms and reduce all-cause mortality in heart failure. However, BivP is subject to the variable coronary sinus(CS) anatomy and LV-pacing lead fail to be implanted in 5%-10% of patients due to the lack of appropriate target branch, high threshold or phrenic nerve stimulation. Almost 30%-40% of patients with successful implantation show no response. What's more, BivP just corrects the mechanical dyssynchrony caused by LBBB not corrects the LBBB. Recent studies have demonstrated that His bundle pacing (HBP) can correct LBBB, achieve physiological pacing and realize the cardiac resynchronization. But HBP has high technical requirements, lower sense value and higher threshold of correcting LBBB, which may be further increased in long-term follow-up. The lastest research shows that pacing left ventricular septum using a transseptal approach can reduce left ventricular(LV) electrical dyssynchrony. Huang et al first confirmed that left bundle branch pacing(LBBP) can correct LBBB and improve cardiac function. LBBP has been reported to offer higher success rate with higher sense value and lower pacing thresholds compared with HBP. In chronic heart failure patients with LBBB that need cardiac resynchronization therapy(CRT), LBBP can achieve the similar electrical and mechanical resynchronization as well as HBP. There is to date no randomized studies between LBBP and BivP in HFrEF patients with complete LBBB that need CRT. The purpose of this study is to compare the therapeutic effects of LBBP and conventional BivP on LV function and clinical endpoints in such patients. The present study will randomize 40 patients in two centres to LBBP or BivP. Baseline assessments including echocardiography parameters[left ventricular ejection fraction(LVEF ), left ventricular end-systolic volume(LVESV), left ventricular end-diastolic volume(LVEDV)], electrocardiogram(ECG), N-terminal pro B-type natriuretic peptide(NT-proBNP) level, New York Heart Association(NYHA) class, 6-minute walking distance(6MWD) and quality of life score(QOL) will be obtained. At the same time, the LBBP and BivP success rate, intraoperative and postoperative complications are recorded.

Official Title
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Comparison Between Left Bundle Branch Pacing and Biventricular Pacing for Cardiac Resynchronization Therapy in Heart Failure(LBBP-RESYNC)

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Procedure: Left bundle branch pacing
* Procedure: Biventricular pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF≤35% as assessed by echocardiography and NYHA class II-IV despite optimal medical therapy for at lest 3 months； Sinus rhythm, complete left bundle branch block (QRS duration ≥130ms)； Between the ages of 18 and 80； With informed consent signed. Exclusion Criteria: After mechanical tricuspid valve replacement； Unstable angina, acute MI, CABG or PCI within the past 3 months; Persistent atrial fibrillation without atrioventricular block, the expected percentage of ventricular pacing below 95%; Enrollment in any other study； A life expectancy of less than 12 months； Pregnant or with child-bearing potential; History of heart transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBBP group<br>In this arm, An right artrial (RA) lead and an implantable cardioverter defibrillator (ICD) lead are conventionally implanted. A left bundle branch pacing(LBBP) lead is attempted to be placed. If LBBP failed, a left ventricular(LV) pacing lead is implanted instead. | Procedure: Left bundle branch pacing<br>* Successful LBBP was defined as (1) LBBP lead is located at 1.5-2cm from His-bundle towards right ventricular apex; (2) Paced QRS morphology of right bundle branch delay(CRBBD) in lead V1; (3) Stimulus to the peak of R wave in V5 and V6 QRS wave, which represents left ventricular activation time(Stim-LVAT), is less than 100ms and constant at high and low output pacing; (4) Unipolar pacing threshold<1.5V/0.5ms; (5) Recording P potential when narrow QRS escape rhythm or CRBBB escape rhythm(not essential).<br>|
| Active Comparator: BivP group<br>In this arm, an RA lead , an ICD lead and a LV pacing lead are placed. If the implantation of LV pacing lead is unsuccessful due to unavailable coronary sinus branches(venae cordis magna or venae cordis media is not recommended), capture above 3.5V/0.5ms or refractory phrenic nerve stimulation,a LBBP lead is placed instead. | Procedure: Biventricular pacing<br>* Implantation of a LV pacing lead is attempted using the standard-of-care technique first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiography parameters(LVEF,LVESV and LVEDV) | Changes in LVEF,LVESV and LVEDV between baseline and follow-up | Baseline; 6-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paced QRS duration | Paced QRS duration is evaluated postoperative day 1 and 1 months, 3 months and 6 months after implantation. | Postoperative day 1; 1-month,3-month and 6-month follow-upP | 
| Changes in concentration of NT-proBNP in blood between baseline and follow-up | Blood test is performed at each time frame to determine the concentration of NT-proBNP(unit: pg/mL) | Baseline; 1-month,3-month and 6-month follow-up | 
| Changes in New York Heart Association Heart Function Classification between baseline and follow-up | The higher the classification, the more severe the heart failure symptoms(four levels: I, II, III and IV) | Baseline; 1-month,3-month and 6-month follow-up | 
| Changes in 6-minute Walk Distance between baseline and follow-up | Distance that a participant walk within 6 minutes | Baseline; 1-month,3-month and 6-month follow-up | 
| Change in Quality Of Life Questionnaire score between baseline and follow-up | Reflect the effect of heart failure on quality of life, and higher scores represent a worse outcome | Baseline; 1-month,3-month and 6-month follow-up | 
| Incidence of clinical adverse events | Including date and number of all-cause mortality, heart failure hospitalization, cardiovascular hospitalization and malignant ventricular arrhythmia | 6-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac resynchronization therapy, chronic heart failure, left bundle branch pacing, biventricular pacing