PracticeUpdate Cardiology March 2019

EDITOR’S PICKS 8

Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome JACC: Heart Failure

COMMENT By Francesco Pelliccia MD, PhD P atients with takotsubo syndrome (TTS) are commonly believed to have a good long-term outcome after the index episode. However, a new meta-analysis demonstrates that long-term rates of overall mortality and recurrence in patients discharged after TTS hospitalization are not trivial. The interesting new and important findings of this pooled analysis of 54 studies involving a total of 4679 patients with TTS were that the annual rate of total mortality was 3.5%, with a 1.0% annual rate of recurrence. In addition, meta- regression analysis showed that some presenting features (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long-term prognosis. This study, therefore, will be very useful to clinicians because it will help to iden- tify the subset of patients discharged alive after an episode of TTS who are more likely to experience a worse out- come in the long term. On the basis of the results of the new study, the possi- bility exists that stronger triggers (eg, physical stressor) that occur in more vul- nerable patients (eg, older adults) might result in a larger extent of myocardial damage, which, in turn, could lead to global left ventricular stunning in the acute phase (eg, atypical ballooning) and eventually to a worse outcome in the long term. episode of TTS who are more likely to experience a worse outcome in the long term. " " This study…will help to identify the subset of patients discharged alive after an

Take-home message • This systematic review and meta-regression analysis used data from 4679 patients with takotsubo syndrome (TTS) to examine long-term outcomes. The median fol- low-up was 28 months, and most (4077) of the patients were women. Although only 2.4% of patients died during the index admission, approximately 10% of surviving patients (464) died during the follow-up. The majority of deaths (351) after the index admission were due to noncardiac causes. The annual rate of recurrence was 1.0%. The yearly mortality rate did not vary significantly by length of follow-up, and there was a 3.5% annual rate of total long-term mortality. There were associations between the presence of a physical stressor, older age, and having atypical bal- looning and an increased risk of long-term mortality. • Although TTS is often considered benign, these findings suggest that it may have non-trivial risks of long-term mortality and recurrence that should be the subject of future prospective studies.

Abstract 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 pre- senting 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 stud- ies 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). Dur- ing a median follow-up of 28months (interquartile range: 23 to 34months), 464 of 4,567 patients who the survived index admission died (103 because of cardiac causes and 351 because of noncar- diac 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 heter- ogeneity (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 fea- tures (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long-term prognosis. Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome: A Systematic Review and Meta-Regression Study. JACC Heart Fail 2019 Jan 02;[EPub Ahead of Print], F Pelliccia, V Pasceri, G Patti, et al. www.practiceupdate.com/c/78280

Dr. Pelliccia is Professor of Cardiology at Sapienza University School of Medicine in Rome, Italy.

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