Dying from Takotsubo syndrome at a young age: the crucial role of brain-heart interactions

Takotsubo syndrome (TTS) is characterized by severe left ventricular dysfunction that typically recovers spontaneously within days or weeks [1]. TTS is typically described in association with sudden and severe emotional or physical stressors [2]. Symptoms, clinical signs, and echocardiographic and electrocardiographic findings in TTS patients are suggestive of an acute coronary syndrome [3]. At presentation, patients usually complain of chest pain and dyspnea, but TTS can also present as syncope and pulmonary edema. Cardiac arrest, cardiogenic shock, and serious ventricular arrhythmias occur more rarely in TTS patients. The most frequent finding on the admission electrocardiogram is ST-segment elevation, which most often is present in the precordial leads. Typically, TTS patients manifest modest increases in creatine kinase-MB and cardiac troponin concentrations as compared to myocardial infarction patients. Of interest, in TTS, there is a disparity between the degree of biomarker elevation and extent of myocardial dysfunction observed on left ventriculography. Diagnostic coronary angiography shows normal coronary arteries or non-obstructive coronary artery disease in the vast majority of patients [4]. Different patterns of LV dysfunction have been reported in TTS, including the classical apical variant, a mid-ventricular variant, a basal or inverted variant and regional variants. The prognosis of TTS was initially thought to be benign. Subsequent series, however, 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 frequency comparable to that of ST-elevation myocardial infarction in the era of primary percutaneous coronary interventions. A recent meta-analysis of clinical correlates of acute mortality in TTS reported that the average in-hospital mortality is 4.5% [5]. Japanese investigators have recently pointed out that TTS is associated with an elevated in-hospital mortality due to co-existing chronic comorbidities and acute medical illnesses [6]. Of note, major adverse events, including cardiogenic shock, cardiac arrest and mortality, are more frequent in women than in men with TTS.
About 90% of patients with TTS are post-menopausal females with a similar prevalence across ethnic groups [7]. Conversely, the occurrence of TTS in the young is very uncommon. Recently, Urbinati et al. performed a systematic review of...


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