COMparisons of Different Procedural endPoints in pAtients Who undeRgo Left Bundle Branch arEa Pacing: Direct Capture of Left Ventricular Conduction SYstem Versus Left veNtricular Septal Capture (COMPARE-SYNC): A Multicenter, Prospective, Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 300
- 主要终点
- Change from baseline in left ventricular ejection fraction (LVEF) at 12 months
研究概览
简要总结
This is a prospective, multicenter, randomized controlled trial designed to determine whether direct capture of the left ventricular conduction system must be achieved as the procedural endpoint of left bundle branch area pacing (LBBAP), or whether left ventricular septal capture alone is sufficient to obtain comparable clinical outcomes.
A total of 300 patients aged 19 years or older who have a guideline-based indication for permanent pacemaker implantation for bradyarrhythmia, an expected ventricular pacing burden of 40% or more, and a planned LBBAP procedure will be enrolled at 5 or more centers in the Republic of Korea. Participants will be randomly assigned in a 1:1 ratio, stratified by baseline left ventricular ejection fraction (LVEF <50% versus >=50%), to one of two procedural strategies:
- LBBP mandatory group - the implanting operator continues the procedure, repositioning the lead as required, until left bundle branch pacing (LBBP) or left fascicular pacing (LFP) is confirmed by at least one predefined conduction system capture criterion.
- LVSP enough group - the operator may complete the procedure at his or her discretion once left ventricular septal pacing (LVSP) is confirmed, irrespective of whether direct conduction system capture is achieved.
The same commercially approved lead and pulse generator platform is used in both groups, so the randomized variable is the procedural endpoint strategy rather than the device.
The primary outcome measure is the absolute change in LVEF from baseline to 12 months, adjudicated by a blinded central echocardiography core laboratory. Secondary outcome measures include echocardiographic response, pacing-induced cardiomyopathy, procedure-related major complications, procedure and fluoroscopy time, paced QRS duration, acute procedural success, achievement and long-term maintenance of conduction system capture, all-cause death, cardiovascular death, heart failure hospitalization, upgrade to cardiac resynchronization therapy, and new-onset atrial fibrillation.
All participants are followed for 12 months after implantation, with study visits at 2 weeks to 1 month, 6 months, and 12 months. The primary analysis follows the intention-to-treat principle, with a prespecified per-protocol analysis according to whether conduction system capture was actually achieved.
详细描述
- BACKGROUND AND RATIONALE
Conventional right ventricular (RV) pacing produces a heterogeneous, left bundle branch block-like pattern of ventricular depolarization that results in electromechanical dyssynchrony. Over the long term this is closely associated with pacing-induced cardiomyopathy (PICM), heart failure, atrial fibrillation, and increased mortality. Conduction system pacing (CSP), which directly stimulates the native conduction system, was developed to overcome these limitations and comprises His bundle pacing (HBP) and left bundle branch area pacing (LBBAP).
LBBAP, first described in 2017, has spread rapidly because it provides lower and more stable capture thresholds, superior sensing parameters, and a higher procedural success rate (approximately 91%) compared with HBP. LBBAP is an umbrella term for capture of the left ventricular subendocardial septal region and includes three subtypes:
- Left bundle branch pacing (LBBP): capture of the pre-divisional left bundle, activating all fascicles simultaneously; LBB potential-to-QRS interval 34 to 25 ms; stimulus to V6 R-wave peak time (S-V6RWPT) <75 ms.
- Left fascicular pacing (LFP): capture of an individual fascicle (left anterior, left septal, or left posterior) or its distal portion; potential-to-QRS interval <25 ms; paced QRS axis may change.
- Left ventricular septal pacing (LVSP): capture of left ventricular septal myocardium without direct activation of the left conduction system; terminal R-wave present in lead V1; conduction system capture criteria not met.
A substantial proportion of published LBBAP studies do not rigorously separate LBBP from LVSP, or define LBBAP success simply as reaching the septum, thereby mixing the two entities. In the Prague CSP trial (Heart Rhythm 2025), 12% of attempted LBBAP procedures resulted in deep septal pacing, and in the CSPOT study (Circ Arrhythm Electrophysiol 2024), 44% of procedures classified as successful LBBAP were in fact LVSP.
Mechanistically, LBBP guarantees physiological ventricular depolarization by directly activating the left conduction system, whereas LVSP depends on myocardial conduction and may not provide the same degree of electrical synchrony. Conversely, LVSP offers advantages in procedural simplicity, threshold stability, and shorter procedure time, and several studies have found no significant difference in clinical outcomes between LVSP and LBBP. A prospective randomized controlled trial is therefore required to determine whether direct conduction system capture must be mandated during LBBAP, or whether achieving LVSP alone is clinically sufficient. 2. OBJECTIVE
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
- Single (Outcomes Assessor)
盲法说明
The implanting operator cannot be blinded because allocation determines the procedural endpoint. Outcome assessment is blinded: all echocardiographic studies are read by a central echocardiography core laboratory whose readers are blinded to treatment allocation, participating site, and acquisition time point, with baseline and 12-month studies read as pairs in randomly ordered time points. All electrocardiograms and intracardiac electrograms are independently re-adjudicated by a central ECG committee blinded to allocation. Both core laboratories operate independently of the investigators and the sponsor.
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a guideline-based indication for permanent pacemaker implantation for bradyarrhythmia and an expected ventricular pacing burden (VP) of 40% or more.
- •Patients in whom a left bundle branch area pacing (LBBAP) procedure is planned in accordance with the above indication.
- •Age 19 years or older.
- •Provision of written informed consent to participate in the study.
排除标准
- •Inability to understand the study or unwillingness to consent to participation.
- •History of mechanical tricuspid valve replacement.
- •History of myocardial infarction involving the interventricular septum.
- •Life expectancy of 12 months or less.
- •Inability to complete 12 months of follow-up for any reason.
- •History of cardiac transplantation.
- •Indication for cardiac resynchronization therapy (CRT), defined as LVEF <=35% and QRS duration >=130 ms with left bundle branch block and NYHA functional class II to IV. This population is the subject of a separate randomized CRT trial and is distinct from the non-CRT pacemaker population studied here.
- •Presence of an existing permanent pacemaker, implantable cardioverter-defibrillator, or CRT device (procedures performed for device replacement are not eligible).
研究组 & 干预措施
LVSP enough group
Participants undergo LBBAP in which left ventricular septal capture alone is accepted as the procedural endpoint. Once deep septal placement within the left ventricular subendocardial region is confirmed together with a terminal R-wave in lead V1 (LVSP), the operator may complete the procedure at his or her discretion irrespective of whether direct conduction system capture is achieved. Voluntary additional lead advancement in an attempt to obtain conduction system capture is permitted but not required.
干预措施: LBBAP with left ventricular septal capture as the accepted procedural endpoint (LVSP) (Procedure)
LBBP mandatory group
Participants undergo LBBAP in which direct capture of the left ventricular conduction system is mandatory. The procedure continues until left bundle branch pacing (LBBP) or left fascicular pacing (LFP) is confirmed by at least one predefined conduction system capture criterion. If conduction system capture cannot be obtained at the initial site, the lead is repositioned and the attempt repeated; more than three attempts are generally not recommended, with the final decision left to the operator. Failure to achieve conduction system capture is recorded as a protocol deviation.
干预措施: LBBAP with mandatory left ventricular conduction system capture (LBBP or LFP) (Procedure)
结局指标
主要结局
Change from baseline in left ventricular ejection fraction (LVEF) at 12 months
时间窗: Baseline and 12 months (±3 months) after implantation
Absolute change in LVEF (percentage points) from baseline to 12 months, compared between the LBBP mandatory group and the LVSP enough group. LVEF is measured by the Simpson biplane method on transthoracic echocardiography and is determined by a central echocardiography core laboratory whose readers are blinded to treatment allocation, participating site, and acquisition time point. Baseline and 12-month studies are read as pairs by the same reader with the time point order randomly presented, in order to minimise measurement error in the change score. Only core laboratory values are used in the analysis; values reported by the enrolling site are collected for reference only. The primary analysis is an analysis of covariance with 12-month LVEF as the dependent variable and treatment group, baseline LVEF, and the stratification factor as covariates.
次要结局
- Echocardiographic response rate at 12 months (proportion achieving LVESV reduction >=15%)(Baseline and 12 months (±3 months))
- Incidence of pacing-induced cardiomyopathy (PICM), composite definition(Baseline and 12 months (±3 months))
- Incidence of procedure-related major complications(From procedure through 12 months)
- Procedure time (min)(Day of procedure (intraprocedural))
- Fluoroscopy time (min)(Day of procedure (intraprocedural))
- Paced QRS duration at 12 months (ms)(12 months (±3 months))
- Acute procedural success rate of LBBAP(Day of procedure (intraprocedural))
- Rate of achieved left bundle branch (conduction system) capture, both groups(Day of procedure (intraprocedural))
- Long-term maintenance of LBBAP and of conduction system capture through 12 months(Immediately post-procedure, 6 months (±3 months), and 12 months (±3 months))
- All-cause death(From procedure through 12 months)
- Cardiovascular death(From procedure through 12 months)
- Heart failure hospitalization (HFH)(From procedure through 12 months)
- Upgrade to cardiac resynchronization therapy (CRT)(From procedure through 12 months)
- New-onset atrial fibrillation(From procedure through 12 months)
- Learning curve of procedure time and fluoroscopy time by operator experience(From first to last enrolled participant, up to 24 months of enrollment)