Myocardial edema and microvascular dysfunction in takotsubo syndrome - insights from cardiac magnetic resonance imaging and invasive coronary physiology

Background: takotsubo syndrome (TTS) is a transient heart failure condition. Its pathophysiology is not fully elucidated, and the role of microvascular dysfunction (MD) is debated. Methods: the project has been divided into two propaedeutic steps including i) systematic review of the literature on MD and TTS performed according to PRISMA guidelines and ii) a retrospective analysis of our institutional TTS registry to investigate myocardial injury in relation to systolic dysfunction, myocardial and systemic inflammation. Later, we performed a prospective study jointly analyzing MD and myocardial edema during the acute phase. MD was assessed invasively at the time of coronary angiography with the calculation of the index of microvascular resistance (IMR). CMR within in-hospital stay was used to assess myocardial edema through parametric imaging (T2 mapping). Results: the systematic review was performed analyzing n=35 studies and highlighted the nonubiquitous presence of MD in TTS, ranging from 35% to 100%, and its association with left ventricular ejection fraction (LVEF) and long-term prognosis. The retrospective study identified admission LVEF (β=-0.524, p<0.001), T2 mapping (β=0.171, p=0.045), Neutrophil-to-lymphocyte ratio (β=0.262, p=0.032), and lymphocyte-to-monocyte ratio (β=-0.282, p=0.033) as independent correlates of troponin release in n=94 patients. In the prospective study we assessed invasive coronary physiology in n=8 patients. IMR was >25 in 3 patients only, and correlated with LVEF (rho= -0.731, p=-0.040). Non-significant relationships were observed between IMR, myocardial edema, injury nor surrogate markers of systemic inflammation. Conclusions: systolic dysfunction is at the core of TTS pathophysiology, strongly interconnecting with all others key markers including myocardial injury, MD and myocardial edema that could be identified as secondary epiphenomenon of the disease.