Objective: To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM) patients based on cluster analysis, and to explore the risk factors for cardiovascular composite events. Methods: This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024. These patients were divided into two clusters using cluster analysis, based on genetic information, demographic information and clinical information. During the follow-up period, cardiovascular composite events were defined as all-cause death and hospitalization for heart failure. Both cardiovascular composite events and all-cause death were the endpoints. Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the incidence of cardiovascular composite events. Results: A total of 43 patients were included in this study, 30 were male (69.8%). In cluster 1 (n=27), whose age of onset was (49.9±13.9) years old, 24(88.9%) of them started with neuropathy or gastrointestinal symptoms, and all clinical phenotypes were mixed type (neurological and cardiac). In cluster 2 (n=16), whose age of onset was (59.0±10.6) years old, 15(93.8%) of them started with heart failure symptoms, and 13(81.3%) were pure cardiomyopathy. During the median follow-up time of 2.6 years, a total of 16 patients (37.2%) experienced composite cardiovascular events, and a total of 12 patients (27.9%) died. Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events (log-rank P=0.04) and all-cause death (log-rank P=0.04) in cluster 2 than in cluster 1. Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate, left ventricular ejection fraction≤40%, and moderate to severe mitral regurgitation were risk factors for vascular composite events (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40% was an independent risk factor (P<0.01). Conclusions: Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM. Cluster 2, which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period. The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%. Cluster analysis is helpful for clinical identification of high-risk groups.
目的： 基于聚类分析探讨遗传型转甲状腺素蛋白淀粉样变心肌病（hATTR-CM）患者的临床特征及预后评估，并分析其发生心血管复合终点事件的危险因素。 方法： 本研究为回顾性队列研究，纳入2000年1月至2024年1月就诊于北京协和医院且被确诊为hATTR-CM的患者。采用聚类分析，根据遗传信息、人口统计学信息以及临床信息将患者分成2类。随访期间心血管复合事件包括全因死亡和心力衰竭住院，以心血管复合事件或全因死亡作为终点事件，绘制Kaplan-Meier生存曲线并采用log-rank法比较聚类分析亚组对不良预后的预测意义。采用单因素和多因素Cox比例风险回归模型分析心血管复合终点事件的相关危险因素。 结果： 本研究共纳入43例患者，男性30例（69.8%）。第1类患者共27例，发病年龄（49.9±13.9）岁，24例（88.9%）以神经病变/消化道症状起病，临床表型均为混合型（心肌病变+周围神经病变）；第2类患者共16例，发病年龄（59.0±10.6）岁，15例（93.8%）以心力衰竭症状起病，13例（81.3%）临床表型为单纯心肌病型。中位随访时间2.6年，共16例（37.2%）患者发生心血管复合事件，12例（27.9%）患者死亡。Kaplan-Meier生存曲线显示，第2类患者以心血管复合事件（log-rank P=0.04）和全因死亡（log-rank P=0.04）为终点的累积生存率低于第1类患者。单因素Cox比例风险回归模型分析显示，估算的肾小球滤过率减低、左心室射血分数≤40%、中重度二尖瓣反流是hATTR-CM患者发生心血管复合事件的危险因素（P均<0.05）。多因素Cox比例风险回归模型分析显示左心室射血分数≤40%是hATTR-CM患者发生心血管复合事件的独立危险因素（P<0.01）。 结论： 聚类分析对hATTR-CM患者预后具有较好的预测价值，第2类hATTR-CM患者（发病较晚且以心力衰竭症状起病）的心脏结构和功能破坏更重，预后更差。hATTR-CM患者发生心血管复合事件与左心室射血分数≤40%相关，聚类分析有助于临床识别高危人群。.