Background: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized.

Objectives: The aim of the present study is to describe TTS sex differences.

Methods: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger.

Results: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; p= 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; p= 0.01; pulmonary diseases 21% vs 15%; p= 0.006; malignancies 25% vs 13%; p< 0.001) and physical trigger (55 vs 32% p< 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both p< 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: p< 0.001; matched: p= 0.001); mortality rate after 60 days was higher in men in the overall (p= 0.002) but not in the matched cohort (p= 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52). Conclusions: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.