Investigating the Impact of Early Valve Surgery on Survival in Staphylococcus aureus Infective Endocarditis Using a Marginal Structural Model Approach: Results of a Large, Prospectively Evaluated Cohort

Background: The impact of valve surgery on outcomes of Staphylococcus aureus infective endocarditis (SAIE) remains controversial. We tested the hypothesis that early valve surgery (EVS) improves survival by using a novel approach that allows for inclusion of major confounders in a time-dependent way. Methods: EVS was defined as valve surgery within 60 days. Univariable and multivariable Cox regression analyses were performed. To account for treatment selection bias we additionally used a weighted Cox model (marginal structural model, MSM) that accounts for time-dynamic imbalances between treatment groups. To address survivor bias EVS was included as time-dependent variable. Follow-up of patients was one year. Results: 203 patients were included in the analysis, fifty patients underwent EVS. All-cause mortality at day 30 was 26%. In the conventional multivariable Cox regression model the effect of EVS on the death hazard was 0.85 (95% CI 0.47-1.52). Using the weighted cox model the death hazard rate of EVS was 0.71 (95% CI 0.34-1.49. In subgroup analyses no survival benefit was observed in patients with septic shock (HR 0.80 [CI 0.26-2.46]), in NVIE (HR 0.76 [CI 0.33-1.71]) or PVIE (HR 1.02 [CI 0.29-3.54]) or in patients with EVS within 14 days (HR 0.97 [CI 0.46-2.07]). Conclusions: Using both a conventional Cox regression model and a weighted Cox model (MSM), we did not find a survival benefit for patients who underwent EVS in our cohort. Until results of randomized controlled trials are available, EVS in SAIE should be based on individualized decisions of an experienced multidisciplinary team.