Left Bundle Branch Pacing as Initial Therapy in Patients With Non-ischemic Heart Failure and Left Bundle Branch Block (LIT-HF Study)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD)
研究概览
简要总结
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.
详细描述
Therapies currently approved to treat heart failure with reduced ejection fraction (HFrEF) have generally shown significant benefit on morbidity and mortality, resulting in strong recommendations in treatment guidelines. Four standard drugs classes, composed of beta-blockers, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor (ACE-I/ARB/ARNI), mineralocorticoid receptor antagonist (MRA) and sodium-glucose co-transporter 2 inhibitor (SGLT2i), have already been standard background therapy in HFrEF. Cardiac resynchronization therapy with pacemaker/Cardiac resynchronization therapy with defibrillation (CRT-P/CRT-D) is an established treatment to HF patients, especially in LVEF ≤35%, sinus rhythm, CLBBB with a QRS duration (QRSd) ≥150 ms, and symptoms on 3-6 months of GDMT. Both the 2021 ESC and the 2022 AHA/ACC/HFSA guidelines for HF included LVEF≤35% after 3-6 months of GDMT as a strong indication for ICD implantation in non-ischemic heart disease.
The traditional biventricular pacing (BiVP) could correct the cardiac dyssynchrony to improve clinical symptoms and reduce all-cause mortality in HF. However, almost 30%-40% of patients with successful implantation show no response and BiVP just corrects the mechanical dyssynchrony caused by LBBB not corrects the LBBB. His Purkinje conduction system pacing (HPCSP) technology has made significant progress in recent five years. His bundle pacing (HBP) and left bundle branch pacing(LBBP) can correct LBBB and achieve physiological cardiac resynchronization only by ordinary single-chamber or dual-chamber pacemaker. LBBP has been reported to produce stable pacing thresholds, adequately sensed R-wave amplitude, and higher likelihood to correct LBBB by pacing more distal to the site of conduction block compared with HBP. The feasibility and efficacy of LBBP for CRT in HF patients with LBBB was demonstrated by previous observational studies showing that LBBP-CRT achieves a narrower QRSd, higher percentage of super responders, and lower pacing thresholds than BiVP-CRT. The LBBP-RESYNC study showed that LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in HF patients with NICM and LBBB.
It remains unclear as to the following questions: 1. After 3-6 months of GDMT, what is the percentage of patients with LVEFs improvement from ≤35% to >35% in HFrEF patients with NICM and CLBBB, and what are the absolute values of the increase in LVEFs; 2. How is the long-term prognosis of those patients with LVEF increased to >35% after GDMT. Whether these patients still need an ICD/CRT-D since they do not fall within the recommendations for primary prevention of sudden cardiac death (SCD); 3. What are the differences of LVEFs changes if LBBP is added to the medical treatment at the beginning.
There are to date no randomized studies comparing GDMT and LBBP combined with GDMT (LBBP+GDMT) as the initial therapy in HFrEF patients with NICM and CLBBB. The purpose of this study is to compare the therapeutic effects of LBBP+GDMT and GDMT on LV function and clinical endpoints in such patients. The present study will randomize about 50 patients in multiple centres to LBBP+GDMT group or GDMT group.
The study is divided into two phases:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
LBBP+GDMT group
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.
干预措施: left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT) (Combination Product)
GDMT group
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.
干预措施: Guideline-Directed Medical Therapy(GDMT) (Drug)
结局指标
主要结局
Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD)
时间窗: 6-month follow-up
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.
次要结局
- Changes in LVEDV(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)
- 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 concentration of NT-proBNP in blood between baseline and follow-up(Baseline; 3-month, 6-month, 12-month, and 18-month follow-up)
- Changes in New York Heart Association Heart Function Classification between baseline and follow-up(Baseline; 3-month, 6-month, 12-month, and 18-month follow-up)
- Change in Quality Of Life Questionnaire score between baseline and follow-up(Baseline; 3-month, 6-month, 12-month, and 18-month follow-up)
- Incidence of clinical adverse events(Baseline; 3-month, 6-month, 12-month, and 18-month follow-up)