Role of coronary microvascular dysfunction in takotsubo syndrome

Takotsubo syndrome (TTS) is an acute and reversible form of heart failure characterised by transient left ventricular (LV) dysfunction in the absence of obstructive coronary artery disease and often triggered by emotional or physical stress. Although the clinical presentation may mimic acute coronary syndrome, the underlying mechanisms remain incompletely understood. Recent evidence highlights coronary microvascular dysfunction (CMD) as a key factor contributing to myocardial ischaemia and transient LV dysfunction in TTS.CMD in TTS appears multifactorial, involving autonomic dysregulation, endothelial dysfunction, inflammation and myocardial oedema, all contributing to transient impairment of myocardial perfusion. Invasive studies consistently demonstrate elevated microvascular resistance and reduced coronary flow reserve during the acute phase, with gradual recovery and improvement in LV function. CMD in TTS has also been associated with adverse prognosis, including higher mortality and persistent LV dysfunction.This narrative review summarises current evidence supporting the pivotal role of CMD in the pathophysiology and prognosis of TTS. We discuss the invasive and non-invasive techniques used to assess CMD, explore the neuro-immune-cardiac interplay underlying TTS and discuss ongoing clinical trials that may refine future diagnostic and therapeutic strategies targeting CMD in TTS.

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Publication Details

Journal
Heart
Published
2026-03-31
DOI
https://doi.org/10.1136/heartjnl-2025-326929
Primary Topic
Takotsubo Cardiomyopathy and Associated Phenomena
Type
article
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article

Role of coronary microvascular dysfunction in takotsubo syndrome

Tim P. van de Hoef, Hilal Khan, Mohamed El Farissi, B Yosofi et al.
Heart
Takotsubo Cardiomyopathy and Associated Phenomena
article

Role of coronary microvascular dysfunction in takotsubo syndrome

Tim P. van de Hoef, Hilal Khan, Mohamed El Farissi, B Yosofi, Rob Eerdekens, Angela H.E.M. Maas, Frederik M. Zimmermann, P Damman, Dana Dawson, Guus de Waard, Robin Nijveldt
article en

Abstract

Takotsubo syndrome (TTS) is an acute and reversible form of heart failure characterised by transient left ventricular (LV) dysfunction in the absence of obstructive coronary artery disease and often triggered by emotional or physical stress. Although the clinical presentation may mimic acute coronary syndrome, the underlying mechanisms remain incompletely understood. Recent evidence highlights coronary microvascular dysfunction (CMD) as a key factor contributing to myocardial ischaemia and transient LV dysfunction in TTS.CMD in TTS appears multifactorial, involving autonomic dysregulation, endothelial dysfunction, inflammation and myocardial oedema, all contributing to transient impairment of myocardial perfusion. Invasive studies consistently demonstrate elevated microvascular resistance and reduced coronary flow reserve during the acute phase, with gradual recovery and improvement in LV function. CMD in TTS has also been associated with adverse prognosis, including higher mortality and persistent LV dysfunction.This narrative review summarises current evidence supporting the pivotal role of CMD in the pathophysiology and prognosis of TTS. We discuss the invasive and non-invasive techniques used to assess CMD, explore the neuro-immune-cardiac interplay underlying TTS and discuss ongoing clinical trials that may refine future diagnostic and therapeutic strategies targeting CMD in TTS.

Heart
Radboud University Nijmegen (NL), University of Aberdeen (GB), Catharina Ziekenhuis (NL), Radboud University Medical Center (NL), University Medical Center Utrecht (NL), St. Antonius Ziekenhuis (NL)
Good health and well-being
Openalex Percentile: Top 27%
Takotsubo Cardiomyopathy and Associated Phenomena
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