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REVIEW ARTICLE

Risk stratification in takotsubo syndrome and its atypical association with diabetes mellitus: A review of current evidence

Javeria Taj1 ,  Moiz Shah Khan2 ,  Hermann Yokolo3* ,  Amer Hammad4 ,  Haris Muhammad5 ,  Aparna Iyer6 ,  Oghenetejir Gbegbaje4 ,  Syeda Hafsa Qadri7 ,  Hafeez Hassan Virk8
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1 Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Sindh, Pakistan
2 Department of Internal Medicine, Ziauddin University, Karachi, Pakistan
3 Department of Research, Medical Research Circle (MedReC), Goma, North Kivu, Democratic Republic of the Congo
4 Department of Internal Medicine, Englewood Medical Center, Englewood, New Jersey, United States of America
5 Department of Cardiology, Newark Beth Israel Medical Center, Newark, New Jersey, United States of America
6 Department of Internal Medicine, Maimonides Medical Center, New York, United States of America
7 Department of Internal Medicine, Dow University of Health Sciences, Karachi, Sindh, Pakistan
8 Department of Cardiology, Adena Greenfield Medical Center, Chillicothe, Ohio, United States of America
Brain & Heart, 025370050 https://doi.org/10.36922/BH025370050
Received: 11 September 2025 | Revised: 11 November 2025 | Accepted: 14 November 2025 | Published online: 2 January 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Takotsubo syndrome (TTS), also known as broken heart syndrome, is an acute cardiac condition with a poorly understood pathophysiology due to its relative rarity. Once considered benign, it is now recognized as a serious disorder with severe complications and a mortality rate comparable to or exceeding that of acute coronary syndrome. This narrative review aims to summarize current knowledge on the prognostic factors associated with TTS, with a particular focus on its relationship with diabetes mellitus (DM). A thorough analysis of 57 relevant studies, selected from over 98,000 articles retrieved from PubMed and Google Scholar, was conducted based on strict inclusion criteria. The findings indicate that advanced age, female sex, pre-existing cardiovascular diseases, and systemic disorders significantly influence the prognosis and mortality of patients with the syndrome. DM plays a paradoxical role, being associated with increased long-term mortality risk while potentially providing a protective effect during the acute phase of the syndrome, possibly by modulating stress responses involved in its onset. Therefore, a deeper understanding of the prognostic implications of TTS and its interaction with diabetes is crucial for developing appropriate risk stratification tools and improving clinical management of patients.

Keywords
Takotsubo syndrome
Atypical association
Diabetes mellitus
Current evidence
Broken-heart syndrome
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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