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

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.

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.

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.

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.