Abstract Body (Do not enter title and authors here): Background
Takotsubo cardiomyopathy (TTS) is a transient cardiac dysfunction often triggered by emotional or physical stress. While sodium-glucose cotransporter-2 (SGLT-2) inhibitors have shown cardioprotective effects in various cardiovascular conditions, their impact on TTS remains unclear. This study aimed to evaluate the long-term outcomes of TTS patients treated with SGLT-2 inhibitors compared to those who were not.

Methods
A retrospective cohort study was conducted using the United States TriNetX platform from 66 healthcare organizations. Patients diagnosed with TTS between 2012 and 2023 were identified and stratified into those initiated on SGLT-2 inhibitors within 14 days of diagnosis and those who were not. Propensity score matching (PSM) was performed on baseline characteristics to balance the cohorts (n=1,318 each). The primary outcomes included all-cause mortality. Secondary outcomes included left ventricular ejection fraction (LVEF) improvement and major adverse cardiovascular events (MACE). Predictors of mortality and LVEF improvement were also analyzed using the Cox proportional hazards model.

Results
After PSM, the TTS-SGLT2 cohort exhibited a significantly lower all-cause mortality rate compared to the TTS-NoSGLT2 cohort (HR=0.741, 95% CI 0.57 - 0.96, p 0.008). LVEF improvement was observed in TTS-SGLT patients (HR 1.55, 95% CI 1.09 - 2.203, p 0.04). Rates of heart failure hospitalizations, cardiogenic shock, and MACE were similar between the groups. Predictors of mortality included male sex, advanced age, diabetes mellitus, chronic kidney disease, hepatic fibrosis, convulsions, peripheral vascular disease, atrial fibrillation, and dementia, whereas predictors of LVEF improvement included younger age, and obesity.

Conclusion
The use of SGLT-2 inhibitors in patients with TTS was associated with a significant reduction in all-cause mortality and a positive impact on LVEF recovery. Further prospective studies are needed to validate these findings and explore the underlying mechanisms.