Physical Triggers in Takotsubo Syndrome: A High-Risk Phenotype? Insights from the EVOLUTION Registry

Background Physical triggers (PT) are increasingly recognized as important determinants of outcomes in Takotsubo syndrome (TS). This multicenter study investigated the prevalence, clinical features, cardiovascular magnetic resonance (CMR) findings, and prognostic impact of PT in patients with TS Methods and results In this retrospective registry, 399 TS patients (mean age 70.1 ± 11.8 years, 91% female) were included with a median follow-up of 26.7 months. A PT was identified in 30.5% of cases, an emotional trigger in 38.8%, and no trigger in 30.5%. Patients with PT showed higher C-reactive protein levels (p=0.008), lower troponin values (p=0.018), less frequent and less extensive T2-STIR abnormalities (p=0.007 and p=0.005, respectively) and LGE (p=0.002 and p=0.005, respectively), longer hospital stays (p=0.002), and more frequent in-hospital complications (p=0.001). Kaplan–Meier analysis demonstrated significantly lower event-free survival in the PT group compared with patients in the emotional or no-trigger groups (log-rank p=0.003). In multivariable Cox regression analysis, the presence of a physical trigger (p=0.037) and pre-existing neurological disease (p=0.027) were independently associated with a higher risk of all-cause mortality and post-discharge adverse events. Conclusion TS patients with PT represent a high-risk subgroup with worse in-hospital outcomes and increased post-discharge events. Careful identification of the trigger type may therefore help stratify risk, allowing for closer monitoring during hospitalization and more vigilant long-term management in the outpatient setting.