Elsevier

International Journal of Cardiology

Volume 267, 15 September 2018, Pages 22-27
International Journal of Cardiology

Natural history and predictors of mortality of patients with Takotsubo syndrome

https://doi.org/10.1016/j.ijcard.2018.04.139Get rights and content

Highlights

  • The prognosis of Takotsubo syndrome is not benign, shows poor outcomes.

  • The prognosis is worse than age- and sex-matched the normal population.

  • The important factor that determines the prognosis is underlying co-morbidity.

  • Cancer is the most important factor affecting prognosis.

  • Treatment with beta blockers and ACE inhibitors do not affect the prognosis.

Abstract

Background

Takotsubo syndrome is a unique transient cardiomyopathy. The pathogenesis, management, and long-term prognosis of Takotsubo syndrome are incompletely understood. The study was designed to evaluate the natural history and determinants of outcomes in patients with Takotsubo syndrome patients.

Methods

We analyzed 265 patients in the Mayo Clinic Takotsubo syndrome registry for clinical presentation, treatment, and long-term outcomes with a focus on identifying prognostic factors for mortality and recurrence.

Results

95% of patients were women with a mean age of 70 ± 11.8 years. Among 257 patients discharged alive, there were 89 (34.6%) deaths, 18 (6.8%) non-fatal myocardial infarction, 12 (4.7%) cerebrovascular accidents and 23 (8.9%) re-hospitalization for heart failure over a mean follow-up of 5.8 ± 3.6 years. Only 4 (5%) patients died from cardiac causes. Cancer was the single leading cause of death. Overall 1-year survival rate was 94.2%. Independent prognostic predictors of mortality were a history of cancer (HR 2.004, 1.334–3.012, p = 0.004), physical stress as precipitating factors (HR 1.882, 1.256–2.822, p = 0.012), history of depression (HR 1.622, 1.085–2.425, p = 0.009) and increased age (HR 1.059, 1.037–1.081, p < 0.001) after multivariate analysis. Beta-blockers and ACE inhibitors at discharge were not significant predictors. There were 24 (9.1%) recurrences during follow-up, but there were no significant differences in medical therapy compared to patients without recurrence.

Conclusion

The high mortality rate is related to non-cardiac co-morbidities such as cancer. Additional determinants include physical stressors, increased age, and history of depression. Use of beta-blockers and ACE inhibitors did not affect development, prognosis or recurrence.

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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