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

Siegbert Rieg; Maja von Cube; Achim J Kaasch; Bastian Bonaventura; Wolfgang Bothe; Martin Wolkewitz; Gabriele Peyerl-Hoffmann; Antje-Christin Deppe; Thorsten Wahlers; Friedhelm Beyersdorf; Harald Seifert; Winfried V Kern

doi:10.1093/cid/ciy908

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

Clin Infect Dis. 2019 Jul 18;69(3):487-494. doi: 10.1093/cid/ciy908.

Authors

Affiliations

¹ Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine and Medical Center.
² Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg.
³ Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf.
⁴ Department of Cardiovascular Surgery, Heart Center, Medical Center, University of Freiburg.
⁵ Department of Cardiothoracic Surgery, University Hospital of Cologne.
⁶ Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne.
⁷ German Centre for Infection Research, Partner Site Bonn-Cologne, Germany.

PMID: 30346527
DOI: 10.1093/cid/ciy908

Abstract

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) that accounts for time-dynamic imbalances between treatment groups. To address survivor bias, EVS was included as a time-dependent variable. Follow-up of patients was 1 year.

Results: Two hundred and three patients were included in the analysis; 50 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% confidence interval [CI], .47-1.52). Using the weighted Cox model, the death hazard rate (HR) of EVS was 0.71 (95% CI, .34-1.49). In subgroup analyses, no survival benefit was observed in patients with septic shock (HR, 0.80 [CI, .26-2.46]), in NVIE (HR, 0.76 [CI, .33-1.71]) or PVIE (HR, 1.02 [CI, .29-3.54]), or in patients with EVS within 14 days (HR, 0.97 [CI, .46-2.07]).

Conclusions: Using both a conventional Cox regression model and a weighted Cox model, 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.

Clinical trials registration: German Clinical Trials registry (DRKS00005045).

Keywords: Staphylococcus aureus; early valve surgery; infectious diseases consultation; infective endocarditis; marginal structural model.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Endocarditis, Bacterial / mortality*
Endocarditis, Bacterial / surgery*
Female
Heart Valves / microbiology
Heart Valves / surgery*
Hospital Mortality
Humans
Male
Middle Aged
Proportional Hazards Models
Prospective Studies
Risk Factors
Selection Bias
Staphylococcal Infections / complications*
Staphylococcal Infections / mortality*
Staphylococcus aureus

Associated data

DRKS/DRKS00005045