LBBP as Initial Therapy in Patients With Non-ischemic Heart Failure and LBBB

NCT05572957 | Recruiting DMC

• 1 other identifier: FirstNanjingMU004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

The present study will recruit 50 symptomatic non-ischemic cardiomyopathy (NICM) patients with left ventricular ejection fraction (LVEF) below 35% and complete left bundle branch block (CLBBB), who have not received complete guideline-directed medical therapy (GDMT). Each patient was randomized to 2 groups, GDMT or left bundle branch pacing combined with GDMT (LBBP+GDMT) as initial therapy and was followed up for 2 phases: 0-6 months (phase I), 7-18 months (phase II). The primary objective is to compare the LVEF change , syncope and malignant ventricular arrhythmias between GDMT group and LBBP+GDMT group, and to observe which strategy will significantly reduce the percentage of recommendations for an implantable cardioverter-defibrillator (ICD) during phase I study. The second outcome measures including health economics, echocardiography parameters\[left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV)\], N-terminal pro B-type natriuretic peptide (NT-proBNP) level, New York Heart Association (NYHA) class, 6-minute walking distance (6MWD), quality of life score(QOL) and incidence of clinical adverse events.

Conditions

Non-ischemic Cardiomyopathy; Heart Failure; Left Bundle-Branch Block

Keywords

Non-ischemic Cardiomyopathy; Heart Failure; Left Bundle-Branch Block; Guideline-Directed Medical Therapy; Left Bundle Branch Pacing; Implantable Cardioverter-Defibrillator; Cardiac Resynchronization Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD)

  After treatment with two strategies(GDMT, LBBP+GDMT), the percentages of LVEF still ≤35% and/or ventricular arrhythmia events was assessed in both groups. That is, the percentage of patients who are eligible for primary/secondary prevention ICD implantation.

  6-month follow-up

Secondary Outcomes (8)

• Health economics

  3-month, 6-month, 12-month, and 18-month follow-up

• Changes in LVEF

  Baseline; 3-month, 6-month, 12-month, and 18-month follow-up

• Changes in LVESV

  Baseline; 3-month, 6-month, 12-month, and 18-month follow-up

• Changes in LVEDV

  Baseline; 3-month, 6-month, 12-month, and 18-month follow-up

• Changes in concentration of NT-proBNP in blood between baseline and follow-up

  Baseline; 3-month, 6-month, 12-month, and 18-month follow-up

Study Arms (2)

GDMT group

ACTIVE COMPARATOR

With the current guidelines of recommended therapies for HF, each patient who meets the inclusion criteria should begin being on all 4 drug classes after enrollment, including a beta-blocker (BB), a RAS inhibitor (ACEI, ARB) or ARNI (preferred), an MRA, and an SGLT2i. The appeal drugs should be gradually uptitrated to the maximum tolerated dose within the first 3-6 months. Ivabradine will be added to the patients whose resting heart rates remain above 70 beats per minute (bpm) after adequate medical treatment, including a BB at maximum tolerated dose.

Drug: Guideline-Directed Medical Therapy(GDMT)

LBBP+GDMT group

EXPERIMENTAL

In this arm, medications are the same as the GDMT group. The LBBP lead is introduced into the right ventricle (RV) and is placed on the right side of the interventricular septum (IVS). The lead is advanced deeply into the IVS until reaching the LV septal subendocardium and right bundle branch block (RBBB) morphology of the paced QRS complex is observed in electrocardiogram (ECG) lead V1. If LBBP fails, his bundle pacing (HBP) should be considered when HBP could correct LBBB. If both of LBBP and HBP fail, conventional BiVP-CRT could be the last option.

Combination Product: left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)

Interventions

Guideline-Directed Medical Therapy(GDMT) DRUG

Quadruple anti-heart failure drug therapy: BB, ACEI/ARB/ARNI, MRA, and SGLT2i. If the initial dose according to guidelines is tolerated, the protocol would then direct the uptitration of medication dose over time to a specified target dose, unless not well tolerated. \*Criteria for \<3 months of optimized (complete) GDMT: 1) according to the latest management of HF, any of the "new quadruple therapy" is not used if the condition allowed; Or 2) the dose of any drug dose not reach the maximum tolerated target; Or 3) under the maximum tolerated dose of BB, ivabradine is not added with a heart rate still ≥70 bpm at rest.

Also known as: Optimal Medical Therapy(OMT)

GDMT group

left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT) COMBINATION_PRODUCT

GDMT is the same as Drug intervention. LBBP is confirmed when: 1) the LBBB morphology disappeared and the paced RBBB pattern (typical or atypical) is observed in V1; and 2) LVAT is ≤100 ms at low output(≤3 V/0.5 ms); and at least 1 of the following is achieved: a) abrupt shortening of LVAT by \>10 ms during mid/deep septal lead placement with a RBBB pattern in V1 at high output, which then remains short and constant at high and low output with further advancement of the lead to the final position; b) transition from nonselective to selective LBBP (QRS morphology transition from atypical RBBB to typical rsR' pattern in V1 and wide/large S-wave in V6 , with the appearance of an isoelectric segment and no LVAT change at high and low outputs); and c) transition from nonselective LBBP to LV septal pacing (lengthening of LVAT by at least 10 ms with or without obvious QRS morphology transition during threshold testing). HBP or BiVP is attempted using the standard-of-care technique.

LBBP+GDMT group

Eligibility Criteria

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

You may qualify if:

• Non-ischemic cardiomyopathy with LVEF≤35% as assessed by echocardiography, NYHA class II-III, and less than 3 months of optimized (complete) GDMT\*;
• Sinus rhythm (paroxysmal atrial fibrillation may be present) with complete left bundle branch block meeting STRAUSS's criteria;
• Between the ages of 18 and 80;
• With informed consent signed.

You may not qualify if:

• After mechanical tricuspid valve replacement;
• Ischemic cardiomyopathy;
• Persistent AF without AV node ablation;
• History of unexplained syncope or indications for pacemaker implantation;
• Indications for ICD implantation such as a history of sustained ventricular tachycardia or sudden cardiac arrest;
• Unstable angina, acute MI, CABG or PCI within the past 3 months;
• Enrollment in any other study；
• A life expectancy of less than 12 months;
• Pregnant or with child-bearing potential;
• History of heart transplantation.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• The First Affiliated Hospital of Dalian Medical University: collaborator
• West China Hospital: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Fujian Medical University Union Hospital: collaborator
• Chinese Academy of Medical Sciences, Fuwai Hospital: collaborator

Study Sites (6)

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

NOT YET RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

NOT YET RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

NOT YET RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

NOT YET RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

NOT YET RECRUITING

Related Publications (5)

• 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.

  PMID: 29173611 BACKGROUND

• 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.

  PMID: 36137670 BACKGROUND

• Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.

  PMID: 31096064 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.

  PMID: 35363499 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Bundle-Branch Block

Condition Hierarchy (Ancestors)

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

Study Officials

• Jiangang Zou, MD,Ph.D

  First Affiliated Hospital, Nanjing Medical University

  PRINCIPAL INVESTIGATOR

• Xiaofeng Hou, MD

  First Affiliated Hospital, Nanjing Medical University

  PRINCIPAL INVESTIGATOR

• Yunlong Xia, MD

  The First Affiliated Hospital of Dalian Medical University

  PRINCIPAL INVESTIGATOR

• Yingxue Dong, MD

  The First Affiliated Hospital of Dalian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiangang Zou, MD,Ph.D

CONTACT

86-13605191407; jgzou@njmu.edu.cn

Xiaofeng Hou, MD

CONTACT

86-13770609205; doctorhou@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: October 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)