Coronary microvascular dysfunction in takotsubo syndrome: An interventional perspective on pathophysiology, diagnostic workflow and prognosis

Takotsubo syndrome (TTS) is an acute, usually reversible left ventricular dysfunction mimicking acute coronary syndrome without a culprit epicardial lesion. Once considered benign, it carries in-hospital mortality comparable to ST-segment elevation myocardial infarction. Coronary microvascular dysfunction (CMD) is frequently observed during the acute phase, but its relationship to TTS remains uncertain: it may be a predisposing substrate, a mediator of catecholamine-induced injury, or a consequence of edema, extravascular compression, altered loading conditions, and ventricular dysfunction, and human evidence shows association rather than mechanism. The index of microcirculatory resistance (IMR) is an established invasive measure of hyperemic microvascular resistance. In TTS, IMR is frequently elevated during the acute phase, and microvascular function appears to improve as left ventricular function recovers, although often incompletely. In a pooled analysis of individual patient data from 166 patients, acute-phase IMR was the only invasive index that remained associated with mortality after adjustment. The cutoff of 54 used in that analysis is an exploratory, hypothesis-generating prognostic threshold: derived within the same dataset, it requires external validation and should be distinguished from the diagnostic threshold of ≥25 used in CMD algorithms that have not been validated in acute conditions such as TTS. Wire-based IMR remains the gold standard; angiography-derived IMR is promising, but available software platforms remain investigational. This review examines proposed mechanisms, measurement methods and their validation, prognostic evidence, and management, and outlines a workflow for future research. We conclude that the clinical utility and optimal timing of invasive coronary function testing in TTS remain uncertain.