Long-term prognosis in Takotsubo Syndrome compared to Heart Failure: Observations from a global federated research network.

INTRODUCTION: To compare long-term outcomes of patients with Takotsubo syndrome (TTS) and heart failure (HF). METHODS: This retrospective observational study used the TriNetX global federated research network. Adult patients (≥18 years) discharged with a diagnosis of TTS (ICD-10-CM I51.81) or HF (I50.x) between 2018 and 2022 were identified. Primary outcomes were 3-year risk of all-cause death, major adverse cardiovascular events (MACE; myocardial infarction or ischaemic stroke), and acute HF. Secondary outcomes included myocardial infarction, ischaemic stroke, ventricular arrhythmias (ventricular tachycardia), malignant arrhythmias (ventricular fibrillation or cardiac arrest), and new-onset atrial fibrillation (AF). Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) before and after 1:1 propensity score matching (PSM). Subgroup analyses were performed by HF phenotype, age (≥65 vs <65 years), and mental health status. RESULTS: The study included 2240 patients with TTS (mean age 62.6 ± 17.3 years; 73.7% female) and 265 564 patients with HF (69.3 ± 14.7 years; 45.8% female). After PSM, TTS was associated with a lower risk of acute HF (HR 0.622, 95% CI 0.539-0.717), ventricular arrhythmias (HR 0.637, 95% CI 0.441-0.919), malignant arrhythmias (HR 0.656, 95% CI 0.571-0.754), new-onset AF (HR 0.672, 95% CI 0.517-0.875), and myocardial infarction (HR 0.818, 95% CI 0.687-0.974), with no significant differences in the remaining outcomes. Differences were greater when TTS was compared with heart failure with reduced ejection fraction. CONCLUSIONS: TTS is associated with lower risk of adverse events than HF. Further research is needed on mental health in its pathogenesis and prognosis.