Natural history and predictors of mortality of patients with Takotsubo syndrome☆
Introduction
Takotsubo syndrome, also known as stress cardiomyopathy, or apical ballooning syndrome was first reported in Japan in 1990 by Sato et al. [1]. Many reports have described clinical features and potential mechanisms, but the precise pathogenesis remains undefined. This is further complicated by the multiple clinical settings and triggers associated with Takotsubo syndrome. Major acute neurological injury such as cerebral hemorrhage, ischemic stroke has long been known to cause neurogenic myocardial stunning [2,3]. The entity of Takotsubo syndrome has extended this to include the syndrome precipitated by extreme emotional and non-neurological physical stressors in postmenopausal women [4,5]. The presence of a precipitating stressor suggests a significant role for the sympathetic nervous system. However, Takotsubo syndrome occurs in the absence of a stressor in as many as one-third cases. The heterogeneity in clinical presentation and incomplete understanding of the pathophysiology has resulted in the absence of the evidence base for guiding management strategy, and current practice is largely based on expert consensus. This includes the use of beta-blockers due to the hypothetical benefit as sympatholytic agents.
Early studies indicated that overall prognosis of Takotsubo syndrome patients was favorable with the long-term prognosis being similar to age, and sex-matched cohorts [6,7]. Recent reports describe less favorable prognosis, with similar survival to acute coronary syndrome [[8], [9], [10]]. Determining the prognosis in individual Takotsubo syndrome patient is uncertain due to limited data on predictive factors. Potential prognostic factors include presenting clinical features, co-morbidities, biomarker values, the severity of left ventricular dysfunction, and use of pharmacological interventions such as beta-blockers and those directed at treating any traditional cardiovascular risk factors.
The aim of this study was to determine the long-term mortality following Takotsubo syndrome and identify independent predictive risk factors associated with mortality and recurrence of Takotsubo syndrome.
Section snippets
Study population
We enrolled patients in the Mayo Clinic Apical Ballooning Syndrome prospective observational registry database from January 2002 through December 2016. This study was approved by the Mayo Foundation Institutional Review Board and informed consent was obtained from each patient. The diagnosis was made according to the Mayo Clinic diagnostic criteria for Takotsubo syndrome [11]. A total 265 patients who met the criteria were enrolled from our hospital registry. Coronary angiography was performed
Baseline clinical characteristics
Clinical characteristics of the 265 patients are described in Table 1. Mean age was 69.9 ± 11.8 years old. Among them, 252 (95%) were women and 77.7% were older than 60 years and 252 (95%) were living in Minnesota. A physical stressor led to the development of Takotsubo syndrome in 116 (45%) patients, more than those triggered by an emotional stressor (59, 23%). A trigger was not identified in 81 (32%) patients. At coronary angiography, 21% patients had one or more significant coronary stenosis
Discussion
Our study demonstrates that the prognosis of Takotsubo syndrome is not favorable, with an overall mortality rate of 34.6% during 5.8 mean follow-up years. The majority of mortality was not directly cardiac related, with non-cardiac co-morbidities being the most common, which could not be prevented by current treatment. The current study suggests a novel approach to preventing events for this high-risk population.
Conclusion
Apical ballooning syndrome is a challenging disease with an increasing incidence. Various clinical presentations and ill-defined pathogenesis lead to diverse outcomes. Our single center registry data with long-term follow-up duration showed high mortality rate associated with non-cardiac cause, which was more strongly related to the patient's underlying demographics and co-morbidities than previously published reports. Hypothetical medical therapy including beta-blockers and ACE inhibitors did
Funding sources
None.
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No conflict of interest.