Microvascular dysfunction in Takotsubo syndrome: a systematic review

Background Microvascular dysfunction (MD) is advocated as one of the main pathogenic mechanisms of Takotsubo syndrome (TTS). Several studies investigated MD in TTS using different techniques; however, no systematic review of these data is currently available.Methods We searched the main scientific database (Embase, Medline, Scopus, PubMed) for articles written in English language using the following keywords: (‘takotsubo’ OR ‘broken heart’ OR ‘apical ballooning’ OR ‘stress cardiomyopathy’) AND (‘microvascular’). Case reports: studies not performed in human subjects or investigating microvascular function in organs other than the heart were excluded.Results 35 studies matched the inclusion criteria. Microvascular function was assessed by standard coronary angiography-derived indexes (n = 17), invasive measurement (n = 10, index of microcirculatory resistance (IMR) in n = 7), echocardiography (n = 5), nuclear medicine (n = 3), and cardiac magnetic resonance imaging (CMR) in n = 2, with some studies applying more than 1 technique. When established cutoff values were used, MD prevalence largely varied (35% to 100%). Although comprehensive clinical correlates were scarcely reported, MD was consistently associated with higher systolic impairment. Blood-based inflammatory biomarkers analysis was performed in one study only, providing inconclusive results. Clinical outcomes associated with MD were reported in four studies including higher rates of major cardiovascular events and long-term mortality.Conclusions MD in TTS has a variable prevalence. It is absent in a relevant proportion of the cases, making it questionable as it should be considered a pre-requisite for disease onset. The presence and extent of MD in TTS is a promising prognostic marker; no data in humans currently confirm its role as a therapeutic target.