心脏淀粉样变性：猝死

Cardiac Amyloidosis: Sudden Cardiac Death

摘要: 轻链型心脏淀粉样变性(AL-CA)是心脏淀粉样变性中最具侵袭性的类型，其特点是疾病进展迅速，心源性猝死率异常高。其病理生理机制涉及双重途径：淀粉样纤维对心肌的机械性浸润，以及循环游离轻链对心肌细胞的直接细胞毒性作用。希氏束–浦肯野传导系统的优先受累，使患者易发生致命性心律失常和传导异常。尽管血液系统治疗取得了进展(包括基于达雷妥尤单抗的方案显著提高了缓解率)，但即使采取预防性器械干预，猝死仍是患者的主要死亡原因。非特异性的临床表现导致诊断延迟，大多数患者就诊时已处于疾病晚期，且已发生不可逆的心脏损伤。通过系统性多器官评估、心脏生物标志物检测及先进影像学技术实现早期识别，对改善预后至关重要。目前的预防策略包括快速实现血液学缓解、合理使用心脏器械以及精细化血流动力学管理。然而，干预的最佳时机和患者选择标准仍未完全明确。本综述总结了目前对AL-CA猝死机制的认知，评估了循证预防策略，强调迫切需要建立早期诊断流程和个体化治疗方案，以降低心源性猝死对此类患者的严重影响。

Abstract: Light-chain cardiac amyloidosis (AL-CA) represents the most aggressive form of cardiac amyloidosis, characterized by rapid disease progression and exceptionally high sudden cardiac death rates. The pathophysiology involves dual mechanisms: mechanical myocardial infiltration by amyloid fibrils and direct cytotoxic effects of circulating free light chains on cardiomyocytes. Preferential involvement of the His-Purkinje conduction system predisposes patients to fatal arrhythmias and conduction abnormalities. Despite advances in hematologic therapies, including daratumumab-based regimens achieving improved remission rates, sudden death remains the predominant cause of mortality even with prophylactic device interventions. The non-specific clinical presentation results in delayed diagnosis, with most patients presenting at advanced stages when irreversible cardiac damage has occurred. Early recognition through systematic multi-organ assessment, cardiac biomarkers, and advanced imaging techniques is crucial for improving outcomes. Current prevention strategies encompass rapid achievement of hematologic remission, judicious use of cardiac devices, and meticulous hemodynamic management. However, the optimal timing of interventions and patient selection criteria remain incompletely defined. This review synthesizes current understanding of sudden death mechanisms in AL-CA and evaluates evidence-based prevention strategies, highlighting the urgent need for early diagnostic algorithms and individualized treatment approaches to reduce the devastating impact of sudden cardiac death in this population.