Department of Ultrasound Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
Department of Cardiology, Jiangyin People's Hospital, Jiangyin, People's Republic of China.
Heart Rhythm. 2024 Aug;21(8):1370-1379. doi: 10.1016/j.hrthm.2024.03.012. Epub 2024 Mar 13.
Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive.
This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM.
LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation.
LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines.
LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM.
左束支传导阻滞（LBBB）是一种常见的传导系统障碍。尽管它广泛存在，但仍存在一个持续的难题，即其与潜在心肌病的复杂关系及其在扩张型心肌病发病中的关键作用。与 LBBB 引起的心肌病（LBBB-CM）相关的病理改变仍不清楚。
本研究旨在探讨 LBBB 致左心室功能障碍的时间动态变化及 LBBB-CM 的病理机制。
通过主左束支干消融建立 14 只犬的 LBBB 模型。所有 LBBB 犬在消融前、消融后 1 个月、3 个月、6 个月和 12 个月进行经食管超声心动图和心电图检查。在 12 个月时进行单光子发射计算机断层扫描成像。然后，从所有 LBBB 犬和 14 只健康成年犬中取出心脏作为正常对照进行解剖观察、浦肯野纤维染色、组织学染色和连接蛋白 43 蛋白表达定量。
LBBB 诱导引起心内膜和心肌中层的显著纤维化改变。浦肯野纤维表现出脂肪变性、空泡化和纤维化，同时连接蛋白 43 蛋白表达下调。在 12 个月的随访中，左心室功能障碍逐渐恶化，在观察期结束时达到峰值。在受 LBBB 影响的犬中观察到心肌功能障碍、灌注不足和纤维化之间的关联。
LBBB 除了传导障碍作用外，还可能导致严重的心肌损伤。左心室功能障碍的时间进展和观察到的病理改变揭示了 LBBB 与心肌病之间的复杂关系。这些发现为 LBBB-CM 的潜在机制和临床意义提供了启示。
