Risk stratification after Takotsubo syndrome: long-term prognostic predictors

Introduction Takotsubo syndrome (TTS) is an acute and reversible form of heart failure, but patients remain at risk for late cardiovascular events. Our aim was to evaluate long-term outcomes after TTS and determine the predictors associated with adverse events. Methods We conducted a retrospective observational study including all patients diagnosed with TTS at a tertiary centre between June 2012 and December 2024. Clinical, laboratory, and echocardiographic data were collected. The primary endpoint was a composite of death from any cause and hospitalization for cardiovascular causes. Predictors of adverse events were evaluated using univariable and multivariable regression analyses. Results We included 124 patients (84.5% women) with a mean age of 72.9±12.9 years. Clinical baseline characteristics are in table 1. At admission, 89.5% of patients were in sinus rhythm, the mean QTc was 467.6±46.4 ms and 47.0% had ST elevation. Also, the most frequent TTS type was apical (86.3), the mean left ventricular ejection fraction (LVEF) was 40.4 ± 10.4% and almost all patients recovered LVEF at discharge (mean LVEF 50.5 ± 11.8%). During hospitalization, 58.9% received angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), 25.0% beta blockers (BB), 13.7% calcium channel blockers (CCB), 36.3% aspirin, 13.7% P2Y12 inhibitors and 18.5% statins. At discharge, ACEi/ARB were prescribed in 83.9%, BB in 65.9%, CCB in 12.9%, aspirin in 45.2%, and statins in 70.2% After a mean follow-up of 3 years, the primary composite endpoint occurred in 25.8% (32 events: 10 hospitalizations for cardiovascular cause and 22 deaths). In univariate analysis (non-parametric), lower haemoglobin at discharge (12.7 vs 11.1), lower peak C reactive protein (2.76 vs 6.5), lower discharge creatinine (0.84 vs 1.22), lower discharge urea (43 vs 55) and lower peak NT-proBNP (4187 vs 15294) were associated with fewer long-term events (p < 0.05 for all)- table 2. No continuous variable was normally distributed. Among categorical variables, BB at discharge reduced risk (HR 0.369, 95%CI 0.146–0.931; p=0.031). In multivariate analysis (adjusted for age, sex, NYHA and admission LVEF), BB therapy remained protective (HR 0.273, 95%CI 0.098–0.763; p=0.013)- graph 1 Discharge urea was an independent predictor (HR 1.026, 95%CI 1.007–1.045; p=0.006)- table 3.However, the number of events was low, so overfitting cannot be excluded. Conclusion In this cohort of TTS patients, discharge beta-blockers reduced 3-year risk of death or CV hospitalization, while higher discharge urea predicted worse outcomes. Results suggest optimizing therapy and monitoring renal function.