Myocardial recovery and critical course in takotsubo syndrome

Background Takotsubo syndrome (TTS) has long been deemed a benign condition of acute reversible cardiac dysfunction with favorable long-term prognosis. This assumption has since been questioned, as TTS has shown outcomes similar to matched ST-segment elevation myocardial infarction cohorts.1 Though acute cardiac dysfunction is often quickly reversible, not all patients recover swiftly and identification of vulnerable TTS patients susceptible to critical in-hospital course remains difficult. Purpose This multicenter analysis of TTS patients aimed to (I) investigate factors associated with short-term recovery of systolic function and wall motion abnormalities (WMAs) and (II) identify vulnerable patients susceptible to critical in-hospital outcomes. Methods Patients diagnosed with TTS between January 2013 and December 2024 were retrospectively analyzed across 13 German tertiary care centers. Stratification by severity of left ventricular (LV) dysfunction at admission (LVEF <40%, 40-49%, and >50%) was undertaken to compare three systolic phenotypes. Conditional on a set of confounders, propensity scores and inverse probability weights (IPW) for LV systolic phenotype (LVEF <40%, 40-49%, or >50%) as an outcome were estimated using multinomial logistic regression models. Multivariable mixed-effects logistic regression models were then fitted to analyze three binary outcomes: (I) in-hospital recovery of LV systolic function and (II) wall motion abnormalities (WMAs) from baseline, as well as (III) critical in-hospital course. Critical course was defined by in-hospital mortality, need for inotropic support, mechanical ventilation, development of cardiogenic shock, or requirement of mechanical circulatory support. Results 488 patients with diagnosed TTS were included for analysis. Median LVEF at admission was 40% [IQR 35, 50]. Apical WMAs (echocardiography (85%), ventriculography (82%), MRI (76%)) were more common than non-apical WMAs (echocardiography (29%), ventriculography (29%), MRI (51%)). 34% of patients achieved recovery of initially recorded WMAs to discharge. In patients with an admission LVEF <40%, only 39% achieved recovery of systolic function (LVEF >50%) to discharge. Factors independently associated with WMA reversal to discharge were higher LVEF at admission and atypical TTS. Higher age was associated with lower odds of LV systolic recovery to discharge. Higher odds of critical in-hospital course were seen in patients with lower admission LVEF, younger age, lower pH, and acute neurologic disease. Conclusion Severity of systolic impairment at presentation is a dominant determinant of both limited early recovery and critical in-hospital course. These findings challenge the assumption of uniform reversibility in TTS and emphasize the need for early risk stratification and awareness for high-risk features and variation in presentations.