Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis

Abstract

: The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart, lack of coronary artery obstruction, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.6 - 2.5% of patients with acute coronary syndrome. The occurrence of takotsubo syndrome is 9 times higher in women, who are aged 60-70 years old , than in men. The hospital mortality among patients with TS corresponds to 3.5% - 12%. In many patients with TS, but not in all, physical or emotional stress precedes the disease. Many patients with TS, but not all, have neurological or mental illnesses. The level of catecholamines is increased in patients with TS, therefore, the occurrence of TS is associated with the excessive activation of the adrenergic system. The negative inotropic effect of catecholamines is associated with the activation of β2 adrenergic receptors. An important role of the adrenergic system in the pathogenesis of TS is confirmed by studies which were performed using 125I-metaiodobenzylguanidine (125I –MIBG). TS causes edema and inflammation of the myocardium. The inflammatory response in TS is systemic. TS causes impaired coronary microcirculation and reduces coronary reserve. There is reason to believe that an increase in blood viscosity may play an important role in the pathogenesis of microcirculatory dysfunction in patients with TS. Epicardial coronary artery spasm is not obligatory for the occurrence of TS. Cortisol, endothelin-1 and microRNAs are challengers for the role of TS triggers. A decrease in estrogen levels is a factor contributing to the onset of TS. The central nervous system appears to play an important role in the pathogenesis of TS.

Catecholamine-Induced Secondary Takotsubo Syndrome in Children With Severe Enterovirus 71 Infection and Acute Heart Failure: A 20-year Experience of a Single Institute

“…Biopsy samples obtained from patients in the acute phase of TTS are similar to those resulting from the direct effects observed after catecholamine-induced cardiotoxicity (16). Evidence from clinical studies supports the hypothesis that excess catecholamine serves as triggers for TTS (15,16,(19)(20)(21). Paur et al (24) reported an animal study concerning TTS that revealed a high epinephrine concentration can induce LV apical ballooning by injecting an exogenously high-dose of epinephrine.…”

“…Catecholamines seem to play an important role in the pathogenesis of TTS, reflecting the comprehensive response of the cardiovascular system to either a sudden increase in the concentration of endogenous catecholamines, which is usually related to acute severe stress, or exogenous catecholamines (15,16,(19)(20)(21). Cases can be classified as primary or secondary TTS (23).…”

“…The pathogenesis of TTS remains largely uncertain. Catecholamine-mediated cardiac stunning may be the main cause ( 15 , 16 , 19 – 21 ). The pathophysiology of TTS appears to be similar to the hypothesis of hypercatecholaminemia-related AHF in severe EV71 infection.…”

SARS-CoV-2-associated Takotsubo is not necessarily triggered by the infection

“…A shortcoming of the study is that no coronary angiography had been carried out. Diagnosing TTS according to the Mayo Clinic criteria requires exclusion of coronary heart disease [2] .…”

“…TTS may be complicated by heart failure [2] , ventricular arrhythmias [2] , or sudden cardiac death [3] . Why was a patient with symptomatic SARS-CoV-2 infection and TTS discharged to home isolation?…”