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Multicenter Study
. 2024 Apr:102:105063.
doi: 10.1016/j.ebiom.2024.105063. Epub 2024 Mar 18.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry

Assem Aweimer  1 , Johannes W Dietrich  2 , Francesco Santoro  3 , Mireia Camins Fàbregas  2 , Andreas Mügge  4 , Iván J Núñez-Gil  5 , Ravi Vazirani  5 , Oscar Vedia  5 , Toni Pätz  6 , Ilaria Ragnatela  3 , Luca Arcari  7 , Massimo Volpe  8 , Miguel Corbì-Pascual  9 , Manuel Martinez-Selles  10 , Manuel Almendro-Delia  11 , Alessandro Sionis  11 , Aitor Uribarri  12 , Holger Thiele  13 , Natale Daniele Brunetti  3 , Ingo Eitel  6 , Thomas Stiermaier  6 , Nazha Hamdani  14 , Mohammad Abumayyaleh  15 , Ibrahim Akin  15 , Ibrahim El-Battrawy  4
Affiliations
Multicenter Study

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry

Assem Aweimer et al. EBioMedicine. 2024 Apr.

Abstract

Background: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry.

Methods: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids).

Findings: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF).

Interpretation: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options.

Funding: This research was not funded by any public, commercial, or not-for-profit agencies.

Keywords: Stress cardiomyopathy; Takotsubo syndrome; Thyroid; Thyrotoxicosis.

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Conflict of interest statement

Declaration of interests JWD received funding and personal fees from Novo Nordisk, VitalAire, Abbott, Medtronic, Oviva, Egetis Therapeutics, myhomecare, aidhere, Ascensia Diabetes Care, Sanofi-Henning, Hexal AG, Bristol-Myers Squibb, and Pfizer, and is the co-owner of the intellectual property rights for the patent “System and Method for Deriving Parameters for Homeostatic Feedback Control of an Individual” (Singapore Institute for Clinical Sciences, Biomedical Sciences Institutes, Application Number 201208940-5, WIPO number WO/2014/088516). IE received funding from Else-Kröner-Fresenius Foundation (No. 2022_EKES.48) and Innovationforum (No. IF-034-22). All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow chart of screened and included cases.
Fig. 2
Fig. 2
Definition of clusters. Thyroid response and pituitary response curves denote the median of thyroid’s secretory capacity (SPINA-GT) and empirical thyrotropic pituitary response.
Fig. 3
Fig. 3
Kaplan–Meier survival curves based on cutoff values derived from phi statistics.
Fig. 4
Fig. 4
Association of clusters with total fatality (left) and time-course of survival (right).
See this image and copyright information in PMC

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