Short- and long-term mortality in Takotsubo syndrome: a nationwide multicentre registry analysis

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. Nevertheless, although a reversible condition, complications such as heart failure, cardiogenic shock, ventricular arrhythmias, and thromboembolic events, occur with relative frequency and significantly impact both short- and long-term prognosis. Several studies have shown morbidity and mortality rates comparable even to those of acute coronary syndromes. Purpose The aim of our study is to evaluate the mortality of TTS in a large nationwide cohort. Methods It is a retrospective observational study based on the Spanish multicentre TTS registry (RETAKO). For this analysis, we included all eligible adult patients registered between January 2012 and May 2025. The primary outcome was all-cause mortality and the secondary outcomes were cardiovascular and non-cardiovascular mortality. Results 2,174 patients were included. The median age was 73 (64-80) years old 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 (147-1,798 days) from the index hospitalization; notably, more than 25% of patients had follow-up beyond 6 years. In-hospital all-cause mortality occurred in 64 patients (2.9%). All-cause mortality was 3.5% (n=76) at 14 days and 3.8% (n=83) at 30 days. During follow-up, mortality increased to 5.2% (n=114) at 6 months and 6.9% (n=150) at 1 year, reaching 12.7% (n=277) at 5 years. Of all deaths, 66 (17.6%) were attributed to cardiovascular causes, 235 (62.8%) to non-cardiovascular causes, and 77 (20.6%) to unknown causes. Among cardiovascular deaths, heart failure and/or cardiogenic shock was the leading cause (n=35, 53.0%), followed by ischemic stroke (n=11, 16.7%), acute coronary syndrome (n=3, 4.5%), bradyarrhythmia (n=2, 3.0%), tachyarrhythmia (n=2, 3.0%), pulmonary embolism (n=1, 1.5%), and other cardiovascular causes (n=12, 18.2%). Conclusion In this large nationwide real-world cohort of patients with Takotsubo syndrome, mortality was not negligible in the short-term and continued to increase during long-term follow-up. Although most deaths were non-cardiovascular, cardiovascular mortality was mainly driven by heart failure and cardiogenic shock. These findings highlight the clinical complexity of Takotsubo syndrome and the need for structured clinical follow-up in this population.All-cause mortality during follow-up.