Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registryResearch in context
Assem Aweimer,
Johannes W. Dietrich,
Francesco Santoro,
Mireia Camins Fàbregas,
Andreas Mügge,
Iván J. Núñez-Gil,
Ravi Vazirani,
Oscar Vedia,
Toni Pätz,
Ilaria Ragnatela,
Luca Arcari,
Massimo Volpe,
Miguel Corbì-Pascual,
Manuel Martinez-Selles,
Manuel Almendro-Delia,
Alessandro Sionis,
Aitor Uribarri,
Holger Thiele,
Natale Daniele Brunetti,
Ingo Eitel,
Thomas Stiermaier,
Nazha Hamdani,
Mohammad Abumayyaleh,
Ibrahim Akin,
Ibrahim El-Battrawy
Affiliations
Assem Aweimer
Cardiology and Angiology Department, Medical Hospital II, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, NRW, Germany; Corresponding author. Department of Cardiology and Angiology Bergmannsheil University Hospital, Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, Bochum 44789, Germany.
Johannes W. Dietrich
Diabetes, Endocrinology and Metabolism Section, Department of Medicine I, St. Josef University Hospital, Ruhr University of Bochum, Bochum, NRW, Germany; Diabetes Centre Bochum/Hattingen, St. Elisabeth Hospital Blankenstein, Im Vogelsang 5-11, Hattingen 45527, Germany; Centre for Rare Endocrine Diseases, Ruhr Centre for Rare Diseases (CeSER), Ruhr University Bochum and Witten/Herdecke University, Alexandrinenstr. 5, Bochum 44791, Germany; Centre for Diabetes Technology, Catholic Hospitals Bochum, Gudrunstr. 56, Bochum 44791, Germany; Centre for Thyroid Medicine, Catholic Hospitals Bochum, Gudrunstr. 56, Bochum 44791, Germany
Francesco Santoro
University of Foggia, Department of Medical and Surgical Sciences, Foggia, Italy
Mireia Camins Fàbregas
Diabetes, Endocrinology and Metabolism Section, Department of Medicine I, St. Josef University Hospital, Ruhr University of Bochum, Bochum, NRW, Germany; Diabetes Centre Bochum/Hattingen, St. Elisabeth Hospital Blankenstein, Im Vogelsang 5-11, Hattingen 45527, Germany; Centre for Rare Endocrine Diseases, Ruhr Centre for Rare Diseases (CeSER), Ruhr University Bochum and Witten/Herdecke University, Alexandrinenstr. 5, Bochum 44791, Germany; Centre for Diabetes Technology, Catholic Hospitals Bochum, Gudrunstr. 56, Bochum 44791, Germany; Centre for Thyroid Medicine, Catholic Hospitals Bochum, Gudrunstr. 56, Bochum 44791, Germany
Andreas Mügge
Cardiology and Angiology Department, Medical Hospital II, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, NRW, Germany
Iván J. Núñez-Gil
Hospital Clínico Universitario San Carlos, Interventional Cardiology, Cardiovascular Institute, Madrid, Spain
Ravi Vazirani
Hospital Clínico Universitario San Carlos, Interventional Cardiology, Cardiovascular Institute, Madrid, Spain
Oscar Vedia
Hospital Clínico Universitario San Carlos, Interventional Cardiology, Cardiovascular Institute, Madrid, Spain
Toni Pätz
University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) and German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
Ilaria Ragnatela
University of Foggia, Department of Medical and Surgical Sciences, Foggia, Italy
Luca Arcari
Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, Italy
Massimo Volpe
Department of Clinical and Molecular Medicine, University of Rome Sapienza and IRCCS San Raffaele Rome, Italy
Miguel Corbì-Pascual
Department of Cardiology, Complejo Hospitalario de Albacete, Albacete, Spain
Manuel Martinez-Selles
Department of Cardiology, Hospital General Universitario Gregorio Marañon, CIBERCV, Madrid, Spain; Universidad Europea, Universidad Complutense, Madrid, Spain
Manuel Almendro-Delia
Servicio de Cardiología, Hospital Virgen de la Macarena, Sevilla, Spain
Alessandro Sionis
Servicio de Cardiología, Hospital Virgen de la Macarena, Sevilla, Spain
Heart Center Leipzig at University of Leipzig and Leipzig Heart Science, Department of Internal Medicine/Cardiology, Leipzig, Germany
Natale Daniele Brunetti
University of Foggia, Department of Medical and Surgical Sciences, Foggia, Italy
Ingo Eitel
University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) and German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
Thomas Stiermaier
University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) and German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
Nazha Hamdani
Institut für Forschung und Lehre (IFL), Department of Molecular and Experimental Cardiology, Ruhr-University Bochum, Bochum, Germany; Institute of Physiology, Ruhr-University Bochum, Bochum, Germany
Mohammad Abumayyaleh
First Department of Medicine, Faculty of Medicine University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany
Ibrahim Akin
First Department of Medicine, Faculty of Medicine University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany
Ibrahim El-Battrawy
Cardiology and Angiology Department, Medical Hospital II, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, NRW, Germany
Summary: 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.
