Early Heparin Initiation Is Associated With Improved Outcomes in Sepsis‑Induced Myocardial Injury: A Target Trial Emulation and Experimental Study
Xiaofei Yin, Xuyang Ji, Zhen Yu, Ruochuan Li, Hao Zhang, Shuxing Wei, Yiming Dong, Yuguo ChenBackground:
The efficacy of heparin therapy in sepsis remains uncertain.
Objective:
To investigate the association between early heparin use and outcomes in patients with sepsis-induced myocardial injury (SIMI) and to explore potential cardioprotective mechanisms in experimental models.
Methods:
The present study employed a target trial emulation (TTE) using data from the MIMIC-IV database to investigate intensive care unit (ICU) patients with SIMI. The cloning-censoring-weighting (CCW) method was used to address immortal time bias. Early heparin use was defined as administration within 72 h of ICU admission. Weighted Cox proportional hazards models were applied to assess its association with 28-day, 90-day, and 365-day all-cause mortality, with sensitivity analyses conducted in the propensity score-matched (PSM) cohort. In parallel, murine SIMI models induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) were used to explore the potential cardioprotective effects of heparin.
Results:
A total of 2,550 patients with SIMI were included. In the TTE analysis, early heparin initiation was associated with lower 28-day mortality (hazard ratio [HR] = 0.786, 95% confidence interval [CI]: 0.700-0.883,
Conclusions:
Early heparin use was associated with reduced mortality in patients with SIMI, while experimental studies suggested potential cardioprotective effects in septic mice.