TakoTsubo Syndrome: First an Acute Coronary Vasculitis and Then Prolonged Myocarditis?

Abstract

Since its initial description by Japanese investigators 30 years ago, TakoTsubo Syndrome (TTS) has variously been regarded as a form of acute coronary syndrome and also as a form of cardiomyopathy (or more accurately, a myocarditis). There is actually good evidence that TTS embodies both of these concepts, and the main purpose of this review is to present data that they occur sequentially. The initial phase of the disorder (over perhaps the first 48 hours post onset of symptoms) represents a form of vasculitis, with associated damage to the endothelial glycocalyx and associated permeabilization of blood vessels. This is followed by a more prolonged phase of myocardial inflammation and oedema, associated with inflammatory activation and energetic impairment within the entire myocardium. Although this phase subsides after several months, it may be followed by longstanding impairment of myocardial function, reflecting residual fibrosis. Understanding of this gradual transition in TTS pathogenesis from vasculature towards myocardium remains an important limitation of patient management, especially as many patients are still told that their hearts have "recovered" within 1-2 weeks. A number of important uncertainties remain. These include development of specific early and ongoing therapeutic strategies to be used to match the sequential pathogenesis of TTS. "And so these men of Indostan Disputed loud and long, Each in his own opinion Exceeding stiff and strong, Though each was partly in the right,

Pivotal role of early coronary microvascular dysfunction in Takotsubo Syndrome

“…The issue of coronary vasculitis as a basis for subsequent myocardial dysfunction in TTS has been appreciated in two previous studies, independent of our previous postulate of sequential pathogenesis (21). In 2020, Montone et al demonstrated in a cohort of 101 TTS patients, that acute coronary flow retardation (TIMI-2 flow) was associated with an increased risk of in-hospital acute heart failure (37).…”

“…Very recently, we have proposed that TTS begins as an acute coronary vasculitis, and evolves into a myocarditis of variable severity and duration (21). However, little has been done to determine whether the putative second phase results from the first.…”

“…TTS therefore appears to present as an acute coronary "vasculitis", and then a subsequent and prolonged myocarditis (21). If this is the case, it is possible, although currently unproven, that the extent of acute coronary vasculitis is a determinant of both severity of subsequent myocarditis (and associated LV systolic dysfunction) and of the risk of severe acute hypotension.…”