Abstract Body (Do not enter title and authors here): Background:
Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction that is strongly triggered by acute emotional or physical stress, although its exact mechanism is unknown. Patients with TTS receive supportive heart failure treatment for the acute phase, however, the use of beta-blockers remains controversial in TTS. Owing to the pathophysiological correlation of catecholamine excess and sympathetic overdrive, the use of beta-blockers does seem logical. No randomized controlled trial has evaluated the efficacy of beta-blockers in TTS; hence, this real-world analysis aims to compare clinical outcomes with beta-blocker use in patients with TTS.

Methods:
Using data from the TriNetX Global Collaborative Network, we identified patients aged ≥18 years with TTS. Patients were categorized into two groups based on their use of beta blockers following TTS diagnosis, and were followed for 1 year, 3 years, and 5 years. 1:1 Propensity-score matching (PSM) was done for 70 baseline variables, including age, sex, race, comorbidities, medications, BMI, laboratory data, and LVEF. The TriNetX platform (TriNetX, LLC, Cambridge, MA) uses logistic regression using “greedy nearest-neighbor matching” with a caliper of 0.1 pooled SDs. Covariates were considered well-balanced when the standardized mean difference (SMD) was less than 0.1. The primary outcome was all-cause mortality. Kaplan-Meier survival curves with log-rank tests were conducted to estimate survival probabilities.

Results:
After PSM, both cohorts had 15,221 patients. Most patients were females (78%) and of white race (72%). Beta blocker use was associated with a significant reduction in all-cause mortality at 1-year [RR: 0.65; 95% CI: 0.61, 0.69; p<0.001], 3-year [RR: 0.74; 95% CI: 0.70, 0.78; p<0.001], and 5-year follow-up [RR: 0.77; 95% CI: 0.73, 0.81; p<0.001].

Conclusion:
Beta blocker use in patients with TTS is associated with a lower risk of all-cause mortality at 1-, 3-, and 5-year follow-ups. Future prospective randomized evidence is necessary to establish the use of beta blockers in patients with TTS.