Epidemiology, pathogenesis, and management of takotsubo syndrome

Abstract

Takotsubo syndrome is a recently recognized acute cardiac disease entity with a clinical presentation resembling that of an acute coronary syndrome. The typical takotsubo syndrome patient has a unique circumferential left (bi-) ventricular contraction abnormality profile that extends beyond a coronary artery supply territory and appears to follow the anatomical cardiac sympathetic innervation. The syndrome predominantly affects postmenopausal women and is often preceded by emotional or physical stress. Patients with predisposing factors such as malignancy and other chronic comorbidities are more prone to suffer from takotsubo syndrome. The pathogenesis of takotsubo syndrome is elusive. Several pathophysiological mechanisms involving myocardial ischemia (multivessel coronary artery spasm, microvascular dysfunction, aborted myocardial infarction), left ventricular outlet tract obstruction, blood-borne catecholamine myocardial toxicity, epinephrine-induced switch in signal trafficking, and autonomic nervous system dysfunction have been proposed. The syndrome is usually reversible; nevertheless, during the acute stage, a substantial number of patients develop severe complications such as arrhythmias, heart failure including pulmonary edema and cardiogenic shock, thromboembolism, cardiac arrest, and rupture. Treatment of precipitating factors, predisposing diseases, and complications is fundamental during the acute stage of the disease. The epidemiology, pathogenesis, and management of takotsubo syndrome are reviewed in this paper.

Keywords: Acute coronary syndrome; Broken heart syndrome; Left ventricle ballooning; Neurogenic stunned myocardium; Takotsubo.

Fig. 1

Left ventriculography during the acute stage of takotsubo syndrome shows typical midapical ballooning during systole (a diastole; b systole). Cardiac magnetic resonance imaging 4 days after left ventriculography shows complete normalization of the left ventricular function (c diastole; d systole)

Fig. 2

An emotional or a physical trigger in predisposed individuals may result in diverse left ventricular contraction patterns (midapical, apical, midventricular, midbasal, basal, focal, and global). The figure is modified from Y-Hassan S and De Palma R [1] with copyright permission

Fig. 3

Trends in reported incidence of takotsubo syndrome from 2006 to 2012. Modified from a table by Minhas AS, Hughey AB, Kolias TJ [13]

Fig. 4

Illustration of cardiac sympathetic hyperactivation disruption at the cardiac sympathetic neurone synapse. Under normal physiologic conditions, when a cardiac sympathetic nerve is stimulated, norepinephrine stored in granules in the presynaptic nerve terminals is released into the synaptic cleft. Norepinephrine stimulates postsynaptic alpha and beta adrenergic receptors on cardiac myocytes, activating downstream effector pathways. In takotsubo syndrome, local cardiac sympathetic overactivation-disruption results in excess and spillover of norepinephrine, causing regional myocardial stunning, as depicted by left ventriculography of two cases showing midapical and midventricular TS. Norepinephrine excess may also inhibit the uptake-1 region, leading to a decrease of norepinephrine reuptake and increase wash-out of norepinephrine into the circulation. The figure is modified from Y-Hassan S. and De Palma R. [1] with copyright permission

Fig. 5

Management of takotsubo syndrome. ATII angiotensin II, CAG coronary angiography, COPD chronic obstructive pulmonary disease, ECG electrocardiogram, IABP intra-aortic balloon pump, HF heart failure, LV left ventricular, LVAD left ventricular assist device, LVD left ventricular dysfunction, LVOTO left ventricular outlet tract obstruction, TdP Torsades de pointes, TS takotsubo syndrome, TTE transthoracic echocardiography, VA-ECMO venoarterial-extracorporeal membrane oxygenation, VF ventricular fibrillation, VT ventricular tachycardia