Abstract

Originally described by Japanese authors in the 1990s, Takotsubo Syndrome (TTS) generally presents as an acute myocardial infarction characterized by severe left ventricular (LV) dysfunction. TTS, however, differs from an acute coronary syndrome because patients have generally a normal coronary angiogram and LV 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 acute and long-term mortality are higher than previously recognized. Indeed, mortality reported during the acute phase in hospitalized patients is ~4-5%, a figure comparable to that of ST elevation myocardial infarction in the era of primary percutaneous coronary interventions. Despite extensive research, the etiology 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 anatomical structures that mediate the stress response are found both in 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 - i.e. direct catecholamine toxicity, adrenoceptor-mediated damage, epicardial and microvascular coronary vasoconstriction and/or spasm, and increased cardiac workload - to myocardial damage whose functional counterpart is the transient apical LV ballooning. The relative preponderance among post-menopausal 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 still remain.