中文摘要

左束支区域起搏（left bundle branch area pacing, LBBAP）是一项由我国原创的新型生理性起搏技术，近年来受到国内外的广泛关注。LBBAP通过直接夺获左束支区域，跨越传导阻滞位点，纠正左束支传导阻滞（left bundle branch block, LBBB），改善或恢复心脏电机械同步性，进而提高心功能。

已有大量临床研究证实，对于具有常规心脏再同步化治疗（cardiac resynchronization therapy, CRT）适应症的心衰患者，即临床指南中Ⅰ类推荐，左心室射血分数（left ventricular ejection fraction, LVEF）小于或者等于35%，同时合并LBBB，QRS波宽度大于或者等于150ms的心衰患者，LBBAP能够显著改善心功能，并降低临床不良事件的发生率。值得注意的是，临床上还存在一部分心衰患者，虽不完全符合常规CRT植入适应症，但其病理生理特征仍提示存在显著的电机械失同步风险，具体表现为持续的心功能不全、预期高起搏比例或心室电机械不同步。这部分患者被指南归入CRT植入的Ⅱa类指征范畴，提示在严格筛选和个体化评估基础上，接受CRT治疗可能带来临床获益。然而，由于现有随机对照研究多聚焦于经典适应症人群，目前关于LBBAP对这类非常规CRT适应症的心衰患者的临床疗效和安全性方面尚不明确，临床证据仍较为有限。

因此，为了填补这一研究空白，进一步探索LBBAP在这部分患者中的临床效果，本研究开展了以下三个方面的分析：第一部分：针对心衰伴LBBB，但LVEF介于36%～50%的轻度收缩功能障碍患者。这类人群因不符合现行指南的CRT强适应症标准，往往错失早期干预时机。我们通过前瞻性、观察性研究，探讨在常规药物治疗基础上，早期接受LBBAP是否能够进一步改善心功能及临床预后。第二部分：针对因长期右室起搏而导致的起搏诱导性心肌病（pacing-induced cardiomyopathy, PICM）患者，比较升级至LBBAP与BiVP在改善心功能和临床预后方面的差异。第三部分：针对合并非LBBB的心衰患者，包括右束支传导阻滞（right bundle branch block, RBBB）或室内阻滞（intraventricular conduction delay, IVCD），评估并对比LBBAP与BiVP治疗对电同步性与心功能的作用。

第一部分：轻度收缩功能障碍合并左束支传导阻滞患者早期接受

左束支起搏的临床疗效

目的：旨在探讨明确在左心室射血分数（left ventricular ejection fraction，LVEF）在35%～50%的轻度收缩功能障碍合并左束支传导阻滞(left bundle branch block, LBBB)的患者中，早期实施左束支起搏（left bundle branch pacing, LBBP）联合指南推荐药物治疗（guideline directed medical therapy, GDMT）的临床疗效，并与单纯GDMT治疗进行比较。

方法：本研究前瞻性连续纳入LVEF在35%～50%、心电图表现为典型LBBB且纽约心功能分级（New York Heart Association, NYHA）II～IV级的轻度收缩功能障碍患者。依据临床决策，患者被分为早期LBBP联合GDMT组（早期LBBP组）和单纯GDMT组。所有患者均接受最大耐受剂量的GDMT。研究终点包括随访6个月时的LVEF、左室舒张末期直径（left ventricular end-diastolic diameter, LVEDD）、NYHA心功能分级，及N末端脑钠肽前体（NT-proBNP）较基线的变化，以及心力衰竭再住院或晕厥等临床事件。对于部分接受了心脏磁共振检查的患者进行亚组分析，依据是否存在合并症或心脏磁共振是否提示晚期钆增强（late gadolinium enhancement, LGE），将早期LBBP组进一步分为“单纯LBBB组”（无其他明确的心肌病病因且LGE阴性）与“LBBB合并组”（伴有缺血性心肌病、房颤、瓣膜病或慢性肾病或LGE阳性），并对比两组接受LBBP的疗效。

结果：研究共纳入54例患者，其中早期LBBP组37例，单纯GDMT组15例，失访2例。6个月随访结果显示，与单纯GDMT组相比，早期LBBP组在LVEF（+14.75±7.37% vs -2.42±2.84%; P < 0.001）, LVEDD（-7.51±5.40mm vs -0.87±4.36mm; P < 0.001）以及NYHA分级（-0.84±0.76 vs -0.13±0.74; P = 0.004）均有显著改善。两组在NT-proBNP水平下降方面差异无统计学意义（-408.83±920.29 pg/ml vs -229.05±1579.17 pg/ml; P = 0.610）。在平均20.68±13.55个月的随访期间，早期LBBP组未出现任何复合临床事件，而单纯GDMT组的事件发生率高达40.0%（P < 0.001）。亚组分析显示，单纯LBBB组患者在LVEF改善和LVEDD降低方面获益更为显著，优于伴有其他合并症或LGE阳性的LBBB合并组。

结论：对于轻度收缩功能障碍合并LBBB的心力衰竭患者，早期实施LBBP联合GDMT较单纯GDMT可显著改善心脏功能，促进心室逆转重塑，并降低心力衰竭再住院及其他不良临床事件的发生率。

第二部分：右心室起搏诱发心肌病患者升级左束支区域起搏与

双心室起搏的疗效比较

目的：起搏诱导性心肌病（pacing-induced cardiomyopathy，PICM）常见于需要高比例右心室起搏（right ventricular pacing, RVP）的患者。目前左束支区域起搏（left bundle branch area pacing, LBBAP），包括左束支起搏（left bundle branch pacing, LBBP）和左心室间隔起搏（left ventricular septal pacing, LVSP），是否在临床疗效上优于传统的双心室起搏心脏再同步化治疗（biventricular pacing - cardiac resynchronization therapy, BiVP-CRT）尚不明确。本研究旨在评估PICM患者中LBBAP与BiVP升级治疗的疗效差异。

方法：本前瞻性、双中心、观察性研究连续纳入接受LBBAP或BiVP升级的PICM患者。将LBBAP组又进一步细分为LBBP和LVSP。随访期间评估超声心动图参数、NT-proBNP水平、纽约心功能分级（New York Heart Association, NYHA）及临床事件（全因死亡、心力衰竭住院、恶性室性心律失常）进行了评估。

结果：研究最终纳入并分析78例患者，其中LBBAP组40例（LBBP 30例，LVSP 10例），BiVP组38例。在6个月随访时，LBBAP组患者的左心室射血分数（left ventricular ejection fraction, LVEF）改善显著优于BiVP组（9.59±7.48% vs 4.91±7.73%; P = 0.008），且LBBP组改善幅度较LVSP组更大（10.62±7.28% vs 6.47±7.57%; P = 0.002）。在平均20.5±12.5个月随访期间，两组临床事件发生率无显著差异。亚组Kaplan-Meier分析显示，与LBBP组相比，BiVP组（调整后风险比adjusted hazard ratio, aHR = 5.56 [1.16-26.71], P = 0.032）及LVSP组（aHR = 12.20 [2.19-68.04], P = 0.004）的全因死亡或心力衰竭住院风险，以及BiVP（aHR = 8.60 [1.13-65.40], P = 0.038）和LVSP（aHR = 15.33 [1.68-139.67], P = 0.015）的心力衰竭住院风险均较LBBP组更高。

结论：PICM患者升级为LBBAP或BiVP后具有相似的临床结局，但升级至LBBP的临床疗效优于BiVP和LVSP。

第三部分：左束支区域起搏与双心室起搏在心衰合并非左束支传导阻滞的

宽QRS波患者中的临床疗效对比

目的：左束支区域起搏（left bundle branch area pacing, LBBAP）作为生理性起搏技术，在心衰合并左束支传导阻滞（left bundle branch block, LBBB）患者中的疗效已得到证实。然而，其在心衰合并非左束支传导阻滞（non-LBBB）的宽QRS波患者中的作用仍缺乏足够循证支持。本研究旨在评估并对比LBBAP与双心室起搏（biventricular pacing, BiVP）在此类人群中的临床疗效及安全性。

方法：本研究回顾性纳入2018年12月到2023年12月期间于我院成功接受LBBAP或BiVP的心衰合并non-LBBB的宽QRS波患者。比较LBBAP组及BiVP组患者基线与术后6个月的超声参数、纽约心功能（New York Heart Association， NYHA）分级、NT-proBNP水平及起搏参数，并记录复合临床事件（全因死亡、心衰再住院或恶性室性心律失常事件）。

结果：共纳入47例患者，包括13例LBBAP组患者与34例BiVP组患者。LBBAP组患者中5例（38.5%）成功实现左束支起搏（left bundle branch pacing, LBBP），另8例（61.5%）证实为左室间隔部起搏（left ventricular septal pacing, LVSP）。LBBAP组患者术后起搏QRS波宽度显著缩窄（167.8±29.0 vs 142.3±20.1ms，P=0.006）。与基线相比，LBBAP组患者术后6个月NT-proBNP水平较前明显下降（1962.5±3219.8 pg/ml vs 4654.2±4595.8 pg/ml, P = 0.002），左心室射血分数（left ventricular ejection fraction, LVEF）显著提升（36.0±7.4% vs 42.9±9.1%, P = 0.012），且三尖瓣返流程度得到改善（0.9±0.8 vs 1.6±0.9, P < 0.001），但左心室舒张末径（left ventricular end-diastolic diameter, LVEDD）、及NYHA分级等指标无显著差异。经逆概率处理加权（inverse probability of treatment weighting, IPTW）校正后，两组患者基线特征大致相当，而术后6个月时LBBAP组患者的LVEF更高（42.9±9.1% vs 33.3±8.8%, P = 0.002），两组在LVEDD、NYHA分级、NT-proBNP水平、三尖瓣返流等方面无显著差异。随访期间患者起搏参数（起搏阈值、感知及阻抗）保持稳定。LBBAP组患者经过22.5±13.4个月的随访共6例（46.2%）发生复合临床事件，无手术或器械相关并发症发生。BiVP组患者经过25.3±15.8个月随访共12 例(35.3)发生复合临床事件，其中4名患者出现5例并发症。

结论：在非LBBB的宽QRS波心衰患者中，LBBAP能够缩短起搏QRS波宽度，实现电同步优化，并改善左室收缩功能，且安全性良好，有望成为传统BiVP的有效补充策略。

Abstract

In recent years, left bundle branch area pacing (LBBAP), an innovative physiological pacing technique pioneered in China, has garnered significant attention. By directly capturing the left bundle branch area, LBBAP bypasses conduction block sites, corrects left bundle branch block (LBBB), and improves or restores electromechanical synchrony, thereby enhancing cardiac function.

Numerous clinical studies have demonstrated that for heart failure patients meeting conventional cardiac resynchronization therapy (CRT) indications—specifically, those with a Class I guideline recommendation, left ventricular ejection fraction (LVEF) ≤35%, LBBB, and QRS duration ≥150 ms—LBBAP significantly improves cardiac function and reduces adverse clinical events. Notably, a subset of heart failure patients exists who do not fully meet conventional CRT implantation criteria but exhibit pathophysiological features indicating significant electromechanical dyssynchrony, such as persistent cardiac dysfunction, anticipated high pacing burden, or ventricular electromechanical dyssynchrony. These patients fall under the Class IIa indication for CRT implantation in current guidelines, suggesting potential clinical benefits with CRT therapy following rigorous screening and individualized assessment. However, as existing randomized controlled trials predominantly focus on populations with classic indications, evidence regarding the clinical efficacy and safety of LBBAP in heart failure patients with non-conventional CRT indications remains limited.

To address this research gap and further explore the clinical utility of LBBAP in these populations, this study conducted analyses across three key dimensions: Part I: Focused on heart failure patients with LBBB and LVEF of 36%–50% (mild left ventricular systolic dysfunction). These patients often miss early intervention opportunities due to not meeting current guideline criteria for CRT Class I indications. Through a prospective observational study, we investigated whether early LBBAP combined with guideline-directed medical therapy could further improve cardiac function and clinical outcomes. Part II: Examined the differences between upgrading to LBBAP versus BiVP in patients with pacing-induced cardiomyopathy (PICM) secondary to long-term right ventricular pacing, focusing on improvements in cardiac function and clinical outcomes. Part III: Evaluated the effects of LBBAP on electromechanical synchrony and cardiac function in heart failure patients with non-LBBB wide QRS complexes, including those with right bundle branch block (RBBB) or intraventricular conduction delay (IVCD). This comprehensive investigation aims to expand the clinical application scope of LBBAP and refine patient selection strategies for diverse heart failure populations.

Part I: Early left bundle branch pacing in heart failure with mild left ventricular systolic dysfunction and left bundle branch block

Objective: To investigate the clinical efficacy of early left bundle branch pacing (LBBP) combined with guideline-directed medical therapy (GDMT) compared with GDMT alone in patients with heart failure with mild left ventricular systolic dysfunction and left bundle branch block (LBBB).

Methods: This study prospectively and consecutively enrolled patients with left ventricular ejection fraction (LVEF) of 35%–50%, typical LBBB on electrocardiogram, and New York Heart Association (NYHA) class II–IV. Based on clinical decision-making, patients were divided into an early LBBP combined with GDMT group (early LBBP group) and a GDMT-alone group. All patients received maximally tolerated GDMT. Study endpoints included changes in LVEF, left ventricular end-diastolic diameter (LVEDD), NYHA class, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline at 6-month follow-up, as well as clinical events such as heart failure rehospitalization or syncope. Subgroup analysis was performed in patients who underwent cardiac magnetic resonance imaging (CMR), categorizing the early LBBP group into a "pure LBBB subgroup" (no identifiable cardiomyopathy etiology and negative late gadolinium enhancement [LGE]) and an "LBBB-comorbidity subgroup" (with ischemic cardiomyopathy, atrial fibrillation, valvular disease, chronic kidney disease, or positive LGE) to compare therapeutic outcomes.

Results: A total of 54 patients were enrolled, including 37 in the early LBBP group, 15 in the GDMT-alone group, and 2 were lost to follow-up. At 6-month follow-up, the early LBBP group demonstrated significant improvements in LVEF (+14.75±7.37% vs. -2.42±2.84%; P<0.001), LVEDD (-7.51±5.40 mm vs. -0.87±4.36 mm; P<0.001), and NYHA class (-0.84±0.76 vs. -0.13±0.74; P=0.004) compared to the GDMT-alone group. No significant difference was observed in NT-proBNP reduction (-408.83±920.29 pg/ml vs. -229.05±1579.17 pg/ml; P=0.610). During a mean follow-up of 20.68±13.55 months, no composite clinical events occurred in the early LBBP group, whereas the GDMT-alone group had an event rate of 40.0% (P<0.001). Subgroup analysis revealed that the pure LBBB subgroup exhibited greater improvements in LVEF and LVEDD reduction compared to the LBBB-comorbidity subgroup.

Conclusion: Early LBBP combined with GDMT significantly improves cardiac function, promotes ventricular reverse remodeling, and reduces heart failure rehospitalization and adverse clinical events in patients with mild left ventricular systolic dysfunction and LBBB compared to GDMT alone.

Part II: Effectiveness of upgrading to Left Bundle Branch Area Pacing compared with Biventricular Pacing in Patients with Right Ventricular Pacing-Induced Cardiomyopathy

Objective: Pacing-induced cardiomyopathy (PICM) is common in patients requiring high-burden right ventricular pacing (RVP). The efficacy of left bundle branch area pacing (LBBAP), including left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP), compared to traditional biventricular pacing cardiac resynchronization therapy (BiVP-CRT) remains unclear. This study aimed to evaluate the therapeutic differences between LBBAP and BiVP upgrade in PICM patients.

Methods: This prospective, dual-center, observational study consecutively enrolled PICM patients upgraded to LBBAP or BiVP. The LBBAP group was further subdivided into LBBP and LVSP. Echocardiographic parameters, NT-proBNP levels, NYHA class, and clinical events (all-cause mortality, heart failure hospitalization, malignant ventricular arrhythmias) were assessed during follow-up.

Results: A total of 78 patients were analyzed, including 40 in the LBBAP group (30 LBBP, 10 LVSP) and 38 in the BiVP group. At 6-month follow-up, LVEF improvement was significantly greater in the LBBAP group than in the BiVP group (9.59±7.48% vs. 4.91±7.73%; P=0.008), with the LBBP subgroup showing greater improvement than the LVSP subgroup (10.62±7.28% vs. 6.47±7.57%; P=0.002). During a mean follow-up of 20.5±12.5 months, no significant difference in clinical event rates was observed. Subgroup Kaplan-Meier analysis demonstrated that BiVP (adjusted hazard ratio [aHR]=5.56 [1.16–26.71], P=0.032) and LVSP (aHR=12.20 [2.19–68.04], P=0.004) were associated with higher risks of all-cause mortality or heart failure hospitalization compared to LBBP. Similarly, BiVP (aHR=8.60 [1.13–65.40], P=0.038) and LVSP (aHR=15.33 [1.68–139.67], P=0.015) showed higher risks of heart failure hospitalization than LBBP.

Conclusion: LBBAP and BiVP upgrades yield similar clinical outcomes in PICM patients, but LBBP demonstrates superior efficacy compared to BiVP and LVSP.

Part III: Comparison of Efficacy between Left Bundle Branch Area Pacing and Biventricular Pacing in Heart Failure Patients with Non-LBBB

Objective: Left bundle branch area pacing (LBBAP), a physiological pacing technique, has proven effective in heart failure patients with LBBB. However, its role in heart failure patients with non-LBBB wide QRS complexes remains understudied. This study evaluated the clinical efficacy and safety of LBBAP in this population.

Methods: This retrospective study included heart failure patients with non-LBBB wide QRS complexes who successfully underwent LBBAP or biventricular pacing (BiVP) at our institution between December 2018 and December 2023. Echocardiographic parameters, NYHA class, NT-proBNP levels, pacing metrics, and composite clinical events (all-cause mortality, heart failure rehospitalization, malignant ventricular arrhythmias) were compared between baseline and 6-month follow-up.

Results: 47 patients were enrolled, including 13 in the LBBAP group and 34 in the BiVP group. Among LBBAP patients, 5 (38.5%) achieved left bundle branch pacing (LBBP) and 8 (61.5%) had left ventricular septal pacing (LVSP). LBBAP significantly reduced paced QRS duration (167.8 ± 29.0 ms vs. 142.3 ± 20.1 ms, P = 0.006). At 6 months, LBBAP also reduced NT-proBNP levels (1962.5 ± 3219.8 pg/ml vs. 4654.2 ± 4595.8 pg/ml, P = 0.002), improved LVEF (36.0 ± 7.4% vs. 42.9 ± 9.1%, P = 0.012), and reduced tricuspid regurgitation (0.9 ± 0.8 vs. 1.6 ± 0.9, P < 0.001), with no significant changes in LVEDD or NYHA class. After IPTW adjustment, baseline characteristics were comparable. At 6 months, LBBAP showed higher LVEF than BiVP (42.9 ± 9.1% vs. 33.3 ± 8.8%, P = 0.002), with no significant differences in LVEDD, NYHA class, NT-proBNP, or tricuspid regurgitation. Pacing parameters remained stable. During follow-up (22.5 ± 13.4 months for LBBAP, 25.3 ± 15.8 months for BiVP), composite events occurred in 6 LBBAP patients (46.2%) and 12 BiVP patients (35.3%), with no procedure-related complications in LBBAP and 5 complications in 4 BiVP patients.

Conclusion: In heart failure patients with non-LBBB wide QRS, LBBAP narrows paced QRS duration, optimizes electrical synchrony, improves left ventricular systolic function, and demonstrates favorable safety, positioning it as a potential complement to traditional biventricular pacing.