Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy

https://doi.org/10.1016/j.ijcard.2014.04.221Get rights and content

Highlights

  • Takotsubo cardiomyopathy is associated with only 1.5% annual recurrence rate.

  • ACE inhibitors and angiotensin receptor blockers reduce risk of recurrence.

  • Beta-blocker therapy did not appear to influence recurrence rate.

  • Recurrence occurs more commonly in severe cases of Takotsubo cardiomyopathy.

Abstract

Aim

Takotsubo cardiomyopathy (TTC) is a disorder of myocardial inflammation induced by high catecholamine levels and is associated with acute complications. In the long-term TTC is associated with a risk of single or multiple recurrences, but risk of such occurrences is not clear. We performed a systematic review and meta-analysis to identify and consolidate the evidence on the incidence and clinical correlates of cases of TTC recurrence.

Methods

A comprehensive search of four major databases (EMBASE, OVID Medline, PubMed and Google Scholar) was performed from their inception to first week of Jan 2014. We included original research studies, recruiting ≥ 5 participants, with ≥ 3 months follow-up, published in English language that reported data on recurrence in patients with TTC.

Results

Out of 298 studies searched, 31 cohorts (1664 TTC patients) were included in the analyses. Out of 74 cases of recurrence, with a mean follow-up of 24.5 months (95% CI, 19.3 to 33 months), extensive recurrence data were available for 23 cases. Cumulative incidence of recurrence was approximately 5% at 6 years. Annual rate of recurrence was approximately 1.5%. Furthermore, 14% of cases had recurrent chest pain and 11% reported dyspnea without definite evidence of recurrent TTC. Discharge medications at index admission included β-adrenoceptor antagonists (BB) in 66.8% and ACE inhibitors (ACEi) and ARB in 67.4%. Recurrence rate was independent of clinic utilization of BB prescription, but inversely correlated (r =  0.45, p = 0.016) with ACEi/ARB prescription. Patients with severe TTC at index admission were noted to have more recurrences.

Conclusions

(1) TTC is associated with only 1–2% annual recurrence rate but substantially greater frequency of ongoing symptoms. (2) ACEi/ARB rather than BB may reduce risk of recurrence.

Introduction

Takotsubo cardiomyopathy (TTC) is now a well-known cardiac condition that predominantly affects women and can be associated with acute and chronic complications. Interestingly, TTC was first reported only 25 years ago in Japan and one of the earliest descriptions in humans was even more recent [1]. The acute stage of the disease can be complicated by hypotension, shock, arrhythmias, heart failure and death [2]. While our understanding of acute complication is clear, the knowledge of the natural history and long term TTC complications is limited because of relatively small number and limited follow-up of the patients. Recurrence of TTC is common and is a well reported long term issue in TTC cohort [3]. However, the exact incidence and correlates of recurrence are not known. We therefore performed a meta-analysis and systematic review to determine the global incidence of recurrence of TTC and to consolidate the evidence.

In the current study, we sought to determine utilizing a systematic review/meta-analysis approach the incidence of recurrence of TTC episodes and cause of its variability. We also prospectively evaluated the impact of discharge medications, left ventricular ejection fraction (LVEF) and type of stressor during initial episode on recurrence.

Section snippets

Methods

This systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. We included comparative studies of any design (randomized control trials, cohort, case control and cross sectional). Eligible studies needed to have ≥ 5 patients and a minimum follow-up of 3 months with confirmed documentation of recurrence of TTC. Inclusion of studies was limited to English language and foreign studies where

Results

The literature search on TTC and recurrence yielded 298 citations. The abstracts of all the 298 citations were reviewed and 58 articles were chosen for full text review. Of the 58 articles chosen for the full text review, 34 were selected as per the inclusion and exclusion criteria. Six out of 34 studies were noted to be duplicated (from the same group with overlapping patient data sets) and were excluded. Additional 3 articles were found on the hand search leading to a total of 31 [23], [24],

Discussion

There is general agreement that TTC is usually precipitated by exposure to a “pulse” of released or administered catecholamines [6], [7] and that individual susceptibility varies, being greater in aging females [8]. Furthermore, recurrence of TTC has been noted to be a problem from the earliest series [9] and definite management strategies regarding preventive treatment are awaiting appropriately designed trials. The complex nature of this disorder and lack of clear knowledge of pathogenesis

Acknowledgment

This work was supported in part by research grants from the National Health and Medical Research Council of Australia Grant Number APP 565404. Kuljit Singh and Ranjit Shah are supported in part by PhD scholarship from the University of Adelaide. J. Horowitz is co-inventor of a patent entitled: “Method for preventing and/or treating a stress induced cardiomyopathy” filed by the University of Adelaide.

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    Disclosures: None.

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