LAUSR

Takotsubo was initially reported as heart syndrome exhibiting acute onset with chest pain, ST elevation or depression at electrocardiography, transient apical left ventricular dysfunction, minimal enzymatic release, mimicking acute myocardial infarction, in patients without angiographic stenosis at coronary angiography.1 Initially described by Satoh et al.,2 it was named ‘takotsubo’-shaped cardiomyopathy, due to the short neck, round, flash like left ventricular (LV) apical ballooning resembling the Japanese octopus pot tako-tsubo.3 Despite takotsubo presenting as an acute coronary syndrome, it was initially reported as cardiomyopathy, given the main feature of reversible myocardial dysfunction in the presence of normal coronary arteries and myocardial damage similar to catecholamine-induced cardiomyopathy.4 Furthermore, takotsubo syndrome was also assimilated to a clinical model of stress-related sudden death, since either an internal (emotional) trigger, usually characterized by loss, fear or anger, or an external (physical) trigger, due to exacerbated disorders, procedural, perioperative, acute cerebrovascular accidents, endocrine crisis of pheochromocytoma, could precipitate the syndrome. Therefore, in the first large international registry, the authors named the syndrome ‘takotsubo (stress) cardiomyopathy’.5 However, reversible myocardial dysfunction in the absence of coronary stenosis in a clinical setting resembling acute coronary syndrome may be due to direct myocyte injury with activation of cell survival cascade, but it might also be the result of myocardial stunning due to temporary ischaemia caused by reversible microvascular spasm. Therefore, we performed a pivotal study in women with takotsubo syndrome due to emotional trigger, undergoing myocardial contrast echocardiography 24 h after the acute event and at discharge, both at rest and during adenosine stimulation. We demonstrated a constricted microvascular network within the dysfunctional area that resolved during adenosine challenge along with myocardial dysfunction.6 Thus, at least in these emotional triggered takotsubo patients, reversible microvascular dysfunction is the pathogenetic mechanism of the syndrome, given the predominance of endothelin receptor type A and α1-receptors in the coronary microvasculature, where catecholamine and endothelin exert their vasoconstrictor effect. Since then, takotsubo syndrome has been largely recognized worldwide in several categories of patients, according to Mayo Clinic diagnostic criteria, such as: 1. the presence of a transient abnormality in LV wall motion beyond a single epicardial coronary artery perfusion territory, the absence of obstructive coronary artery disease or angiographic evidence of acute plaque rupture, the presence of new electrocardiographic abnormalities or elevation in cardiac troponin level, and the absence of pheocromocytoma or myocarditis.7 Since a definite trigger cannot be found in almost 30% of cases, emotional or physical stress was not included as a diagnostic criterion. Moreover, absence of reported triggers, especially emotional ones, does not necessarily exclude their occurrence, since they might be either negated or not reported by the patients, or not asked about or overlooked by physician. Nevertheless, in the original report of the international InterTAK registry, apart from takotsubo patients diagnosed according with Mayo Clinic criteria, patients with presence of coronary artery disease, with wall motion abnormalities congruent with a single coronary artery territory and death during the acute phase before wall motion recovery were included.5 In this takotsubo patient series, not only severe in-hospital complications including shock and death were similar to patients with acute coronary syndrome, but also the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year and the rate of death was 5.6% per patientyear. Interestingly, physical triggers, acute neurologic or psychiatric disease, high troponin levels and low ejection Primary and secondary takotsubo syndrome: Pathophysiological determinant and prognosis