Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome: A Systematic Review and Meta-Regression Study

Objectives: This study assessed the incidence of long-term adverse outcomes in patients with Takotsubo syndrome (TTS). Background: The long-term prognosis of TTS is controversial. It is also unclear whether presenting characteristics are associated with the subsequent long-term prognosis. Methods: We searched the PubMed, Embase, and Cochrane databases and reviewed cited references up to March 31, 2018 to identify studies with >6 months of follow-up data. Results: Overall, we selected 54 studies that included a total of 4,679 patients (4,077 women and 602 men). Death during admission occurred in 112 patients (2.4%), yielding a frequency of 1.8% (95% confidence interval [CI]: 1.2% to 2.5%), with significant heterogeneity (I² = 78%; p < 0.001). During a median follow-up of 28 months (interquartile range: 23 to 34 months), 464 of 4,567 patients who the survived index admission died (103 because of cardiac causes and 351 because of noncardiac issues). The annual rate of total mortality was 3.5% (95% CI: 2.6% to 4.5%), with significant heterogeneity (I² = 74%; p < 0.001). Overall, 104 cases of recurrence of TTS were detected during follow-up, yielding a 1.0% annual rate of recurrence (95% CI: 0.7% to 1.3%), without significant heterogeneity (I² = 39%; p = 0.898). Meta-regression analysis showed that long-term total mortality in each study was significantly associated with older age (p = 0.05), physical stressor (p = 0.0001), and the atypical ballooning form of TTS (p = 0.009). Conclusions: Our update analysis of patients discharged alive after TTS showed that long-term rates of overall mortality and recurrence were not trivial, and that some presenting features (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long-term prognosis.