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Epidemiology and pathophysiology of Takotsubo syndrome

This article has been updated

Key Points

  • Approximately 2% of patients who present to hospital with suspected acute coronary syndrome have Takotsubo syndrome, with a predominance in postmenopausal women

  • Mortality is higher than initially thought, and recurrence is seen in 1.2% of patients within 6 months and nearly 5% at 6 years, with no preventive therapy currently available

  • Systemic catecholamine surges can cause acute coronary and peripheral vasospasm followed by peripheral vasodilation; a common complication is cardiogenic shock, due at least in part to left ventricular systolic dysfunction

  • Biopsy samples taken during the acute phase of Takotsubo syndrome show morphological changes similar to those after catecholamine-induced cardiotoxic effects, supporting direct effects as well as vascular influences

  • The apical myocardium of the left ventricle has a high density of β-adrenoceptors and, therefore, is the region most sensitive to circulating catecholamines

  • During extreme stress, excessive epinephrine levels cause a switch from the Gsα stimulatory to the cardioprotective Giα cardioinhibitory secondary messenger pathway within cardiomyocytes, thereby acting as a positive inotrope

Abstract

Takotsubo syndrome is an acute cardiac syndrome first described in 1990 and characterized by transient left ventricular dysfunction affecting more than one coronary artery territory, often in a circumferential apical, mid-ventricular, or basal distribution. Several pathophysiological explanations have been proposed for this syndrome and its intriguing appearance, and awareness is growing that these explanations might not be mutually exclusive. The reversible apical myocardial dysfunction observed might result from more than one pathophysiological phenomenon. The pathophysiology of Takotsubo syndrome is complex and integrates neuroendocrine physiology, potentially involving the cognitive centres of the brain, and including the hypothalamic–pituitary–adrenal axis. Cardiovascular responses are caused by the sudden sympathetic activation and surge in concentrations of circulating catecholamines. The multiple morphological changes seen in the myocardium match those seen after catecholamine-induced cardiotoxicity. The acute prognosis and recurrence rate are now known to be worse than initially thought, and much still needs to be learned about the epidemiology and the underlying pathophysiology of this fascinating condition in order to improve diagnostic and treatment pathways.

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Figure 1: Histopathological features of Takotsubo syndrome.
Figure 2: Integrated pathophysiological model for acute apical dysfunction in Takotsubo syndrome.

Change history

  • 08 June 2015

    In the version of this Review published online ahead of print, the details of the author contributions were missing. The author contributions are now included in the HTML and PDF versions of the article.

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Y.J.A. is supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science.

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Y.J.A. researched data for the article. All authors substantially contributed to discussion of content, wrote, and reviewed and edited the manuscript before submission.

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Correspondence to Yoshihiro J. Akashi.

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Akashi, Y., Nef, H. & Lyon, A. Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 12, 387–397 (2015). https://doi.org/10.1038/nrcardio.2015.39

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