Prognostic performance of the InterTAK Score in a nationwide Takotsubo syndrome registry

Introduction Takotsubo syndrome (TTS) is characterized by transient regional systolic dysfunction, dilatation, and oedema involving most frequently left ventricular apex and/or mid-ventricle in the absence of obstructive coronary disease. It frequently mimics acute coronary syndromes and is associated with significant morbidity and mortality. In 2019, Wischnewsky et al. developed the InterTAK Prognostic Score for the prediction of short- and long-term mortality in this population. However, external validation of the InterTAK Prognostic Score in large nationwide cohorts remains limited. Purpose The aim of our study is to evaluate the prognostic value of InterTAK Prognostic Score in a large nationwide cohort. Methods It is a retrospective cohort study based on the Spanish multicentre TTS registry (RETAKO). For this analysis, we included all eligible patients registered between January 2012 to May 2025. The InterTAK Score was applied at admission following its definition (variables considered consist of: TTS secondary to neurologic disorders; TTS secondary to physical activities, medical conditions or procedures; age; systolic blood pressure; diabetes mellitus; left ventricular ejection fraction; sex; heart rate; and TTS without triggering factor). The discriminative ability of the score was assessed by receiver-operating characteristic (ROC) curves and the area under the curve (AUC). Results 2,174 patients were included. The median age was 73±9 years and 85.5% were women. Cardiovascular risk factors were highly prevalent: hypertension (66.4%), dyslipidaemia (50.9%) and diabetes mellitus (24.4%); though obesity (14.1%) and active smoking (13.5%) were less common. Chronic comorbidities included chronic kidney disease (10.3%), chronic obstructive pulmonary disease (8.6%) and neurological diseases (9.9%). Patients were followed for a median of 657 days (IQR: 147-1,798 days) from the index hospitalization; more than 25% of patients had follow-up extending beyond 6 years. InterTAK score showed poor discrimination for in-hospital mortality (64 deaths, AUC 0.649, Figure 1A), with an optimal cut-off of 22.5 (sensitivity 56%, specificity 70%; OR 3.04, 95% CI 1.84-5.03; p <0.001). In addition, considering 5-year mortality, InterTAK again showed poor performance (277 deaths, AUC 0.629, Figure 1B); the optimal cut-off identified was 16.5 (sensitivity 71%, specificity 53%; OR 2.23, 95% CI 1.72-2.88; p <0.001). Furthermore, in time-to-event analysis (Cox regression), the score InterTAK >16.5 was not significantly associated with 5-year mortality (HR 1.22, 95% CI 0.93-1.60; p = 0.14, Figure 2). Conclusion In this large nationwide real-world cohort, the InterTAK Prognostic Score showed poor discrimination for both short- and long-term mortality and did not independently predict long-term mortality. These findings question its utility for risk stratification in contemporary TTS patients and highlight the need for improved prognostic models.