Age- and sex-based risk stratification in takotsubo syndrome: a Japanese nationwide registry study

Q: What are the key findings of this study?

Male sex (OR 1.59) and older age (OR 1.32 per 5-year increase) were independently associated with higher in-hospital mortality in patients with takotsubo syndrome.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Takotsubo syndrome (n=13585). Intervention: Male sex and older age vs. Female sex and younger age. Primary outcome: In-hospital mortality (OR 1.59, 95% CI 1.30-1.95, p=<0.001).

Q: What does this research mean for the field?

Male sex and older age are independently associated with higher in-hospital mortality and severe adverse events in patients with takotsubo syndrome. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To elucidate age- and sex-specific differences in clinical characteristics, in-hospital management, and mortality outcomes among patients presenting with takotsubo syndrome.

Tomohiro Hayashi; Kazuaki Negishi; Takato Kobayashi; Koshiro Kanaoka; Hozuka Akita; Yuto Shinkura; Ryo Nishio; Kensuke Matsumoto; Masahiko Hoshijima; Satoru Kawasaki; Hogara Nishisaki; Masanobu Okayama; Tsuneaki Kenzaka

doi:10.3389/fcvm.2026.1852892

July 1, 2026Frontiers in Cardiovascular MedicineOpen Access

Age- and sex-based risk stratification in takotsubo syndrome: a Japanese nationwide registry study

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Key result

Male sex linked to ~59% higher in-hospital mortality in takotsubo syndrome.

OR 1.59
95% CI 1.30-1.95
P<0.001
n=13,585

Figures

Why the study?

The prognostic significance of age in takotsubo syndrome remains debated, and evidence regarding male patients is limited.

Do older age and male sex independently predict higher in-hospital mortality in patients with takotsubo syndrome?

Key Points

To elucidate age- and sex-specific differences in clinical characteristics, in-hospital management, and mortality outcomes among patients presenting with takotsubo syndrome.
Analyzed 13,585 patients with a first takotsubo syndrome episode undergoing coronary angiography and meeting Mayo Clinic diagnostic criteria from the nationwide Japanese Registry of All Cardiac and Vascular Diseases–Diagnosis Procedure Combination database (2012–2022).
Stratified the cohort across sex and three age categories (≤50, 51–74, and ≥75 years) to evaluate clinical features and in-hospital management.
Identified independent predictors of in-hospital mortality using multivariable logistic regression analysis.
In-hospital mortality was higher in men than in women across all age groups: ≤50 years (3.0% vs. 1.5%), 51–74 years (4.3% vs. 1.5%), and ≥75 years (8.2% vs. 4.6%).
Multivariable analysis identified older age (OR 1.32 per 5 years; 95% CI 1.26–1.39; P < 0.001) and male sex (OR 1.59; 95% CI 1.30–1.95; P < 0.001) as independent predictors of in-hospital mortality.
Men more frequently presented with comorbidities such as chronic kidney disease and malignancies, and more often required intensive care interventions including catecholamines, mechanical circulatory support, and ventilatory assistance.

Study Design

Type

Cohort (n=13,585)

Multicenter

Yes

Structured PICO

Do older age and male sex independently predict higher in-hospital mortality in patients with takotsubo syndrome?

P

Population

13,585 patients (81.2% female) hospitalized with a first episode of takotsubo syndrome who underwent coronary angiography, evaluated for in-hospital mortality.

O

Outcome

In-hospital mortalityhard clinical

Main Result

Odds Ratio: 1.59 (95% CI 1.3–1.95)

p-value: p=<0.001

In patients with takotsubo syndrome, older age and male sex are independent predictors of in-hospital mortality and are associated with a higher burden of comorbidities and need for intensive care.

Limitations

Retrospective observational study subject to inherent biases.
Administrative database lacking detailed clinical data such as vital signs, laboratory measurements, and echocardiographic findings.
Unable to assess triggering factors or differentiate between primary and secondary forms of TTS.
Could not distinguish cardiovascular from non-cardiovascular mortality.
Post-discharge information was unavailable, precluding evaluation of long-term outcomes.
Absence of detailed clinical variables in the database (e.g., left ventricular ejection fraction, biomarkers, trigger type, presence of left ventricular outflow tract obstruction, and TTS anatomical subtype)
Potential residual confounding
Inability to differentiate between primary and secondary TTS

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

May inform risk stratification by sex and age in takotsubo syndrome; hypothesis-generating pending prospective validation.

Abstract

Background Despite sex-related differences in the clinical presentation and outcomes of takotsubo syndrome (TTS), the prognostic significance of age remains debated, and evidence on male patients is limited. This study elucidated age- and sex-specific differences in clinical characteristics and outcomes of patients with TTS using a large nationwide Japanese registry. Methods We conducted a retrospective cohort study using the nationwide Japanese Registry of All Cardiac and Vascular Diseases–Diagnosis Procedure Combination database (2012–2022). Patients with the first TTS episode, identified by the International Classification of Diseases, 10th Revision codes, who underwent coronary angiography and met the Mayo Clinic diagnostic criteria were included. Clinical characteristics, in-hospital management, and outcomes were compared across age groups (≤50, 51–74, ≥75 years) and sex. Independent in-hospital mortality predictors were assessed using multivariable logistic regression. Results Among 13,585 patients, 2,558 (18.8%) were men, and 523 (3.8%), 5,354 (39.4%), and 7,708 (56.7%) were aged ≤50, 51–74, and ≥75 years, respectively. Men more frequently had comorbidities (chronic kidney disease, chronic obstructive pulmonary disease, malignancies) and required intensive care, including catecholamine administration, mechanical circulatory support, and ventilatory assistance, compared with women. Adverse events increased with age in both sexes. Across age groups, in-hospital mortality was higher in men (≤50 years: 3.0%; 51–74 years: 4.3%; ≥75 years: 8.2%) than in women (≤50 years: 1.5%; 51–74 years: 1.5%; ≥75 years: 4.6%). Multivariable analysis identified older age [odds ratio (OR) 1.32 per 5 years; 95% confidence interval (CI) 1.26–1.39; P < 0.001] and male sex (OR 1.59; 95% CI 1.30–1.95; P < 0.001) as independent in-hospital mortality predictors. Conclusion Older age and male sex were independent predictors of in-hospital mortality in patients with TTS. These findings may help guide risk assessment and clinical monitoring in TTS according to age and sex, although further prospective validation is warranted.

Discussion

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Cite This Study

Hayashi et al. (2026) conducted a cohort in Takotsubo syndrome (n=13,585). Male sex and older age vs. Female sex and younger age was evaluated on In-hospital mortality (OR 1.59, 95% CI 1.30-1.95, p=<0.001). Male sex (OR 1.59) and older age (OR 1.32 per 5-year increase) were independently associated with higher in-hospital mortality in patients with takotsubo syndrome.

synapsesocial.com/papers/6a6caaa1f44fa9f079db5573 https://doi.org/10.3389/fcvm.2026.1852892

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Age- and sex-based risk stratification in takotsubo syndrome: a Japanese nationwide registry study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Age- and sex-based risk stratification in takotsubo syndrome: a Japanese nationwide registry study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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