Coronary Microvascular Dysfunction in Stress Cardiomyopathy: At the Heart of the Problem

Takotsubo syndrome (TTS) is an acute disorder characterized by transient left ventricular dysfunction with typical regional wall motion abnormalities, most commonly apical ballooning. It accounts for 1-3% of all suspected acute coronary syndromes and up to 5-6% in women presenting with ST-segment elevation myocardial infarction requiring coronary angiography to exclude obstructive coronary artery disease. The pathophysiology of TTS is complex and not fully elucidated, with sympathetic hyperactivation playing a central role through calcium dysregulation, oxidative stress, and metabolic alterations. Both clinical and experimental data demonstrate the importance of inflammation, with cell infiltration and persistent immune activation exceeding the acute phase. Increasing evidence highlights the impact of coronary microvascular disfunction (CMVD) as a secondary phenomenon, with some findings that support its role as a causative substrate. Beyond well-known predisposing conditions such as female sex, postmenopausal age, and neurological and psychiatric disorders with the trigger of a physical or psychological event, numerous case reports associate the syndrome with chronic autoimmune diseases, even if clear experimental evidence remains poor and worthy of further study. Echocardiography and advanced imaging techniques, including cardiac magnetic resonance and positron emission tomography, have provided insights into transient CMVD, reversible myocardial edema, and metabolic impairment, strengthening our knowledge of the syndrome as a dynamic process. It is also of growing interest to perform invasive hemodynamic assessment to explain the increase in microvascular resistance. This review offers a comprehensive and up-to-date overview of these techniques in the context of TTS. Since clinically, TTS may be associated with significant morbidity and mortality, with some unexplained cases of long-term myocardial disfunction or even recurrence, a deeper understanding of the interplay between catecholamines, inflammation, immune substrate, and CMVD may improve risk stratification and lead to the development of targeted therapeutic strategies.