Clinical trial NCT04110431: Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy
Official title: Comparison Between Left Bundle Branch Pacing and Biventricular Pacing for Cardiac Resynchronization Therapy in Heart Failure(LBBP-RESYNC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Heart Failure
Keywords: cardiac resynchronization therapy
chronic heart failure
left bundle branch pacing
biventricular pacing
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Fu Wai Hospital, Beijing, China
First posted: 2019-10-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. LVEF≤35% as assessed by echocardiography and NYHA class II-IV despite optimal medical therapy for at lest 3 months；
2. Sinus rhythm, complete left bundle branch block (QRS duration ≥130ms)；
3. Between the ages of 18 and 80；
4. With informed consent signed.

Exclusion Criteria:

1. After mechanical tricuspid valve replacement；
2. Unstable angina, acute MI, CABG or PCI within the past 3 months;
3. Persistent atrial fibrillation without atrioventricular block, the expected percentage of ventricular pacing below 95%;
4. Enrollment in any other study；
5. A life expectancy of less than 12 months；
6. Pregnant or with child-bearing potential;
7. History of heart transplantation.

Primary outcomes:
measure: Echocardiography parameters(LVEF,LVESV and LVEDV)
timeFrame: Baseline; 6-month follow-up
Secondary outcomes:
measure: Paced QRS duration
timeFrame: Postoperative day 1; 1-month,3-month and 6-month follow-upP
measure: Changes in concentration of NT-proBNP in blood between baseline and follow-up
timeFrame: Baseline; 1-month,3-month and 6-month follow-up
measure: Changes in New York Heart Association Heart Function Classification between baseline and follow-up
timeFrame: Baseline; 1-month,3-month and 6-month follow-up
measure: Changes in 6-minute Walk Distance between baseline and follow-up
timeFrame: Baseline; 1-month,3-month and 6-month follow-up
measure: Change in Quality Of Life Questionnaire score between baseline and follow-up
timeFrame: Baseline; 1-month,3-month and 6-month follow-up
measure: Incidence of clinical adverse events
timeFrame: 6-month follow-up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
city: Beijing
country: China
facility: Fu Wai Hospital, Beijing, China
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jiangang Zou, MD,Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol. 2017 Dec;33(12):1736.e1-1736.e3. doi: 10.1016/j.cjca.2017.09.013. Epub 2017 Sep 22.
citation: Hou X, Qian Z, Wang Y, Qiu Y, Chen X, Jiang H, Jiang Z, Wu H, Zhao Z, Zhou W, Zou J. Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum. Europace. 2019 Nov 1;21(11):1694-1702. doi: 10.1093/europace/euz188.
citation: Mafi-Rad M, Luermans JG, Blaauw Y, Janssen M, Crijns HJ, Prinzen FW, Vernooy K. Feasibility and Acute Hemodynamic Effect of Left Ventricular Septal Pacing by Transvenous Approach Through the Interventricular Septum. Circ Arrhythm Electrophysiol. 2016 Mar;9(3):e003344. doi: 10.1161/CIRCEP.115.003344.
citation: Wang Y, Zhu H, Hou X, Wang Z, Zou F, Qian Z, Wei Y, Wang X, Zhang L, Li X, Liu Z, Xue S, Qin C, Zeng J, Li H, Wu H, Ma H, Ellenbogen KA, Gold MR, Fan X, Zou J; LBBP-RESYNC Investigators. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2022 Sep 27;80(13):1205-1216. doi: 10.1016/j.jacc.2022.07.019.