Epidemiology and pathophysiology of Takotsubo syndrome

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, and often in a circumferential apical, mid-ventricular or basal distribution. A number of pathophysiological explanations for this syndrome with its intriguing appearance have been proposed, and there is a growing awareness that these are not mutually exclusive, and that the reversible apical myocardial dysfunction observed could result from more than one pathophysiological phenomenon. The pathophysiology of takotsubo syndrome is complex, with integration of both neuroendocrine physiology involving the cognitive centres of the brain and hypothalamic-pituitary-adrenal axis, and the cardiovascular responses to the sudden sympathetic activation and surge in circulating catecholamines. The latter have been explored in detail, starting with the histological findings at biopsy, with the multiple morphological changes seen in the myocardium matching those seen after established catecholamine cardiotoxic effects. Clinically, both the acute prognosis and recurrence rate are unfortunately worse than previously reported. It is clear that the modern cardiology community has much still to learn regarding the epidemiology and the underlying pathophysiology of this fascinating condition in order to improve diagnostic and treatment pathways. 3 Key points Approximately 2% of all patients presenting to the hospitals with suspected acute coronary syndrome are usually identified with takotsubo syndrome. There is a predominance in post-menopausal women compared to men or younger women. Both the acute and long-term mortality are higher than previously recognized.The cumulative incidence of recurrence increased from 1.2% at first 6 months to nearly 5% at 6 years, and there is no current evidence to support treatment with any specific to prevent recurrence. Systemic surges in catecholamines may cause vascular effects including acute coronary vasospasm and severe acute hypertension due to acute peripheral vasospasm followed by later peripheral vasodilation and hypotension. In the clinical setting, profound hypotension and cardiogenic shock is a common complication, however, it is not solely related to the extent of impairment of left ventricular (LV) systolic function, and thus probably relates in part to inappropriate peripheral vasodilation. Biopsies during acute takotsubo syndrome are characterized by multiple morphological changes that are similar to those after catecholamine cardiotoxic effects supporting a direct effect in addition to the vascular influences. The apical myocardium of the left ventricle has the highest density of β-adrenergic receptors (βAR), and is therefore most sensitive to circulating catecholamines.

Role of echocardiography for takotsubo cardiomyopathy: clinical and prognostic implications

“…A meta-analysis published in 2014 has described that in a 2-year follow-up, 3-8% of TTC patients had recurring its symptoms; requiring particular attention for this fact (7,8,(69)(70)(71)(72). Different LV wall motion disorders in the same patient are also reported; that is, wall motion disorder patterns are not always the same (73,74).…”

“…Its onset is rare; however, its specific features play an important role in diagnosing the chest pain in clinical practice. Transient left ventricular (LV) wall motion abnormalities are peculiar in TTC and these abnormalities are not triggered by obstructive coronary artery disease (3)(4)(5)(6)(7). Post menopausal patients under emotional and physical stress predominantly suffer from this syndrome.…”

An uncommon cause for grade 3 primary graft dysfunction after lung transplantation: Takotsubo cardiomyopathy

“…[1][2][3][4] The dynamic ST/T alterations on ECG in the inferior and lateral leads without reciprocal ST depression in the other leads are the typical feature of TTC, in the absence of epicardial coronary artery disease, pheochromocytoma, or myocarditis. [1,2] Although the exact pathophysiological pathway of TTC still remains unclear, catecholamine-mediated myocardial stunning including an acute multi-vessel coronary spasm and coronary microcirculation dysfunction has been suggested to play a key role. [2] Exposure to emotional or physical stress and exaggerated sympathetic activity leads to secretion of excessive catecholamine production and, therefore, it has been suggested that those catecholamine molecules are directly related with myocardium injury.…”

“…[1,2] It is particularly important for the differential diagnosis of dynamic ECG alterations following lung transplantation (LuTx), due to common occurrence in patients in the intensive care unit, and is often mistaken for other acute cardiac syndromes with poor prognosis. [3] However, TTC associated with LuTx has been reported in a very limited number of patients to date.…”

Recurrence of Takotsubo Cardiomyopathy

“…1 The exact pathophysiology of TC is still unclear, although several hypotheses, such as multivessel coronary spasm, microvascular impairment, and direct catecholaminemediated myocardial stunning, have been proposed. 2 While the prognosis for TC patients is generally favorable, with complete recovery from LV wall motion abnormality, some patients experience recurrence of TC, once or sometimes multiple times. There is little information about the efficacy of chronic pharmacological therapy for preventing TC recurrence.…”