From Department of Cardiovascular Sciences, Sapienza University, Rome, Italy (F.P.); Molecular and Clinical Sciences Research Institute, St George's, University of London, UK (J.C.K.); Institute of Cardiology, Catholic University, Rome, Italy (F.C.); and Vita-Salute University and San Raffaele Hospital, Milan, Italy (P.G.C.).
Circulation. 2017 Jun 13;135(24):2426-2441. doi: 10.1161/CIRCULATIONAHA.116.027121.
Originally described by Japanese authors in the 1990s, Takotsubo syndrome (TTS) generally presents as an acute myocardial infarction characterized by severe left ventricular dysfunction. TTS, however, differs from an acute coronary syndrome because patients have generally a normal coronary angiogram and left ventricular dysfunction, which extends beyond the territory subtended by a single coronary artery and recovers within days or weeks. The prognosis was initially thought to be benign, but subsequent studies have demonstrated that both short-term mortality and long-term mortality are higher than previously recognized. Indeed, mortality reported during the acute phase in hospitalized patients is ≈4% to 5%, a figure comparable to that of ST-segment-elevation myocardial infarction in the era of primary percutaneous coronary interventions. Despite extensive research, the cause and pathogenesis of TTS remain incompletely understood. The aim of the present review is to discuss the pathophysiology of TTS with particular emphasis on the role of the central and autonomic nervous systems. Different emotional or psychological stressors have been identified to precede the onset of TTS. The anatomic structures that mediate the stress response are found in both the central and autonomic nervous systems. Acute stressors induce brain activation, increasing bioavailability of cortisol and catecholamine. Both circulating epinephrine and norepinephrine released from adrenal medullary chromaffin cells and norepinephrine released locally from sympathetic nerve terminals are significantly increased in the acute phase of TTS. This catecholamine surge leads, through multiple mechanisms, that is, direct catecholamine toxicity, adrenoceptor-mediated damage, epicardial and microvascular coronary vasoconstriction and/or spasm, and increased cardiac workload, to myocardial damage, which has a functional counterpart of transient apical left ventricular ballooning. The relative preponderance among postmenopausal women suggests that estrogen deprivation may play a facilitating role, probably mediated by endothelial dysfunction. Despite the substantial improvement in our understanding of the pathophysiology of TTS, a number of knowledge gaps remain.
最初由日本作者在 20 世纪 90 年代描述，Takotsubo 综合征（TTS）通常表现为急性心肌梗死，其特征为严重左心室功能障碍。然而，TTS 不同于急性冠状动脉综合征，因为患者通常有正常的冠状动脉造影和左心室功能障碍，其范围超出单个冠状动脉供血区域，并在数天或数周内恢复。最初认为预后良好，但随后的研究表明，短期死亡率和长期死亡率均高于先前认识。事实上，住院患者急性期的死亡率约为 4%至 5%，这一数字与经皮冠状动脉介入治疗时代 ST 段抬高型心肌梗死相当。尽管进行了广泛的研究，但 TTS 的病因和发病机制仍不完全清楚。本综述的目的是讨论 TTS 的病理生理学，特别强调中枢和自主神经系统的作用。已经确定不同的情绪或心理应激源会先于 TTS 发作。介导应激反应的解剖结构存在于中枢和自主神经系统中。急性应激源会诱导大脑激活，增加皮质醇和儿茶酚胺的生物利用度。在 TTS 的急性期，循环肾上腺素和去甲肾上腺素从肾上腺髓质嗜铬细胞释放，以及局部从交感神经末梢释放的去甲肾上腺素均显著增加。这种儿茶酚胺激增通过多种机制导致心肌损伤，即直接儿茶酚胺毒性、肾上腺素能受体介导的损伤、心外膜和微血管冠状动脉收缩和/或痉挛以及增加心脏工作量，这与短暂的左心室心尖球囊样变具有功能对应关系。绝经后妇女中相对居多的情况表明，雌激素缺乏可能发挥促进作用，可能通过内皮功能障碍介导。尽管我们对 TTS 病理生理学的理解有了实质性的提高，但仍存在一些知识空白。
