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Background: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS)., Methods: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis., Results: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001)., Conclusion: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality., Objectives: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS., Methods: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period., Results: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150)., Conclusions: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Templin has received institutional grants from Abbott Vascular, Medtronic, and SMT; and has received consulting grants from Biotronik, Microport, and Innova. Dr Airaksinen has received grants or has contracts with the Finnish Foundation for Cardiovascular Research; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Pfizer, Boehringer Ingelheim, and AstraZeneca. Dr Bauersachs has received grants from or has contracts with Abiomed, CVRx, Norgine, Roche, and Zoll; holds patents PCT/EP2007/008772 and PCT/EP2009/051986 for microRNA and downstream targets for diagnostics and therapeutic purposes; has received consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche, and Vifor; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, CVRx, Norgine, Novartis, Pfizer, and Vifor. Dr Boehm has received grants from or has contracts with Deutsche Forschungsgemeinschaft research support (DFG, SFB-TTR 219, S-01); has received speaker honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Novartis, Servier, and Vifor; and is on the advisory board of Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Pfizer, ReCor, Servier, and Vifor. Dr Ferreira has received payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from A Menarini, Medinfar, Bayer, AstraZeneca, Biotronik, and Medtronic; and has received payments for participation on a Data Safety Monitoring Board or Advisory Board from Medtronic. Dr Dichtl has received consulting fees from Reata. Dr Kaiser has received consulting fees from the Swiss Federal Office of Public Health; and has received support for attending meetings and/or travel from Medtronic, Abbott, and Europa Organization. Dr Kobza has received institutional grants on behalf of the Luzerner Kantonsspital from Biosense Webster, Boston Scientific, Biotronik, Medtronik, and Sis-Medical; and has received consulting fees from Biosense Webster, Biotronik, and Medtronic. Dr Koenig has received grants and provision of reagents to the institution from Singulex, Dr.Beckmann Pharma, Abbott, and Roche Diagnostics; has received consulting fees from AstraZeneca, Novartis, Amgen, Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, OMEICOS, Daiichi-Sankyo, Novo Nordisk, New Amsterdam Pharma, TenSixteen Bio, Esperion, and Genentech; and has received lecture fees from Bristol Myers Squibb, Novartis, Amgen, Berlin-Chemie, Sanofi, and AstraZeneca. Dr Lüscher has received research or educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi, and Vifor; is the president elect of the European Society of Cardiology; is chairman of the research committee of the Swiss Heart Foundation; is President of the Board of the Zurich Heart House; and is Trustee of the London Heart House. Dr Karakas has received grants or has contracts with Vifor Pharma and Daiichi-Sankyo; has received consulting fees or payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Vifor, Pharmacosmos, and Sphingotec; and has received equipment, materials, drugs, medical writing, gifts or other services from Sphingotec and Vifor Pharma. Dr Niederseer has received consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Gerson Lehmann Group (GLG) Consulting, Novo Nordisk, Pfizer and Zoll; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, and Pfizer; and has received support for attending meetings and/or travel from Abbott, Amgen, Bayer, and Novo Nordisk. Dr Roffi has received institutional research grants from Boston Scientific, Cordis, Terumo, Biotronik, and Medtronic. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; the Department of Cardiology (University Hospital of Zurich/University of Zurich), however, reports research, educational, and/or travel grants from Abbott, Abiomed, Alexion, Amgen, AstraZeneca, At the Limits Ltd, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Concept Medical, Corteria, CSL, Daiichi-Sankyo, Diatools AG, Edwards Lifesciences, Guidant Europe NV, Hamilton Health Sciences, IHF, Innosuisse, Johnson/Johnson, Kaneka Corporation, Kantar, Kiniksa, Labormedizinisches Zentrum, MedAlliance, Medical Education Global Solutions, Medtronic, MicroPort, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, Sorin CRM SAS, SSS International Clinical Research, Stromal, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL. Prof Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; remuneration for the time spent in the following consulting activities were made directly to the University of Zurich and do not impact on his personal remuneration: AstraZeneca (IMC), Bayer, Boehringer Ingelheim, Citi Research, Klub Class, Novo Nordisk, Radcliffe Group, Stiftung Pfizer Forschungspreis, and Vifor; remuneration for the following lectures were made directly to the University of Zurich and do not impact on his personal remuneration: Abbott, Amgen, AstraZeneca (A+ Science AB), Bayer (At the Limits), Boehringer Ingelheim, Boston Scientific (CCE Services), Brigham and Women’s Hospital Boston, C.T.I GmbH, FomF, Hôpitaux Universitaires des Genève (GECORE), Luzerner Kantonsspital, Sanofi-Aventis, Servier, Medcon, Medscape (WebMD), Medtronic, Medworld, Novartis, Roche, Ruwag, Swiss Heart Failure Academy, The Hong Kong Heart Failure Society, Trama Solutions SL, Inselspital Bern, Charité–Universitätsmedizin Berlin (Medical Education Global Solutions), Romanian Society of Cardiology, ÖKG Österreichische Gesellschaft für Kardiologie, and Zoll; has received support for attending meetings and/or travel from AstraZeneca (IMC/A+ Science AB), Boehringer Ingelheim, Centro Hospitaler de Vila Nova de Gaia, C.T.I. GmbH (Universitätsklinikum Düsseldorf), European Society of Cardiology, Monocle, Novartis, Spektar Putovanja, Austrian Heart Failure Association, and Heart Failure Association of the ESC; remuneration for following Advisory Boards were made directly to the University of Zurich and do not impact on his personal remuneration: Bayer, Roche, IMC/AstraZeneca, and Amgen; and he has received secretarial and administrative support of the HFA for his role as President/Past-President for 2018 to 2020. Dr Schunkert has received consulting fees from Amgen, Daiichi-Sankyo, Merck Sharp and Dohme, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Servier; has received honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and support for attending meetings and/or travel from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharp and Dohme, Novartis, Sanofi Aventis, Servier, and Synlab; and has received honoraria for his participation on a Data Safety Monitoring Board or Advisory Board of Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Amgen. Dr Wolfrum has received consulting fees from NVT/Biosensors as well as payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NVT/Biosensors; and has equities in Hi-D Imaging, Winterthur, Switzerland. Dr Crea has received personal fees from Amgen, AstraZeneca, Abbott, Menarini, Chiesi, and Daiichi-Sankyo, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)