Impact of beta-blockers on long-term mortality in takotsubo syndrome

Background Elevated catecholamine levels are considered a key mechanism in takotsubo syndrome (TTS). Although beta-blockers are commonly prescribed, their impact on long-term prognosis remains controversial. Purpose To evaluate the association between beta-blocker therapy at discharge and long-term mortality in patients with TTS. Methods We retrospectively analyzed patients with TTS enrolled in the JapanTAK registry between 2010 and 2021. Among 447 patients, 33 who died during hospitalization and 74 with missing follow-up data were excluded. The remaining 340 patients were classified according to beta-blocker use at discharge. Propensity score matching (1:1) was performed using a multivariable logistic regression model including demographic factors, comorbidities, in-hospital complications, left ventricular ejection fraction, and discharge medications. The primary endpoint was all-cause mortality. Results During a mean follow-up of 3.4 years, 66 patients (19.4%) died. Patients receiving beta-blockers at discharge (n=95, 27.9%) had a higher prevalence of hypertension (66.3% vs. 50.6%, p=0.011) and cardiovascular disease (33.7% vs. 11.4%, p<0.001). In the unmatched cohort, beta-blocker therapy was not associated with long-term mortality (HR 0.87, 95% CI 0.49–1.55; p=0.63). After propensity score matching (50 pairs, 19 events), beta-blocker therapy showed a trend toward lower mortality (HR 0.45, 95% CI 0.17–1.18; p=0.10). Conclusions Beta-blocker therapy at discharge was not significantly associated with improved long-term mortality in TTS. However, propensity score matching suggested a potential reduction in mortality, although the analysis may have been underpowered due to the limited number of events. These findings warrant further investigation in larger prospective studies.