Unfractionated Heparin and the Clinical Outcomes in Takotsubo Syndrome: A Nationwide Cohort Study

Objective Takotsubo syndrome is characterized by transient left ventricular dysfunction, and prophylactic heparin is recommended for high-risk patients to prevent thrombotic events. Although a recent Swedish registry study reported a reduced 30-day mortality with heparin use, the analysis did not consider treatment timing and potential confounders. This study aimed to examine the association between the early administration of unfractionated heparin and the short-term outcomes in patients with Takotsubo syndrome. Methods We conducted an observational study using the Diagnostic Procedure Combination database in Japan from April 2010 to March 2022. Patients Patients diagnosed with Takotsubo syndrome were categorized into two groups: those who received unfractionated heparin initiated within the first 2 days and continued until day 2, and those who did not. The primary outcome was 30-day in-hospital mortality. The secondary outcomes were ischemic events, bleeding events, and blood transfusions. A Cox regression model with inverse probability of treatment weighting (IPTW) adjustment was used to estimate the hazard ratios for the outcomes. Results Among 9,920 eligible patients, 4,127 received unfractionated heparin, and 5,793 who did not were considered as controls. After IPTW adjustment, heparin therapy was associated with a lower risk of 30-day mortality (3.3% vs. 4.3%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.53-0.84; p<0.001). The proportions of ischemic and bleeding complications did not differ between the groups. Conclusion Unfractionated heparin use was associated with a reduced 30-day in-hospital mortality in Takotsubo syndrome without increasing the risk of ischemic or bleeding complications. Further investigation of heparin use in Takotsubo syndrome is therefore warranted.