Characterizing contemporary practices in the approach to elevated troponin I levels during sepsis

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PROJECT SUMMARY/ABSTRACT I propose the “Characterizing contemporary practices in the approach to elevated troponin I levels during sepsis” study to develop an evidenced-based approach to the management of elevated serum troponin levels during sepsis and to advance my skillset in clinical design, data science methodology, statistical programming and professional development in order to become an independent clinical investigator. Sepsis is the result of life-threatening organ dysfunction due to infection and is associated with significant long-term cardiovascular morbidity. Serum troponin levels are frequently elevated during sepsis and are prognostic for post-sepsis cardiovascular complications. Despite its prognostic significance and regular presence during sepsis, there is no standardized management approach to patients with elevated serum troponin levels during sepsis. Decisions regarding cardiovascular diagnostic testing and use of potential cardio-protective medications among these patients are left to the discretion of the treating clinician, resulting in diverse practice approaches with unclear impact on patient outcomes. I propose two essential foundational steps needed to develop a standardized management approach to patients with elevated serum troponin levels during sepsis through the use of a large, observational critical care database: 1) evaluate current practices in cardiovascular diagnostic and therapeutic management of patients with elevated serum troponin levels during sepsis, and 2) assess the risks and benefits associated with use of anti-platelet and anticoagulation strategies as potential cardio- protective treatment agents, among the same sepsis cohort. The first objective will be achieved through practice variation analysis using risk-adjusted hierarchical models to identify the patient-, physician-, and hospital-level factors contributing to cardiac management approach variation. The second objective will be completed through a targeted trial approach using marginal structural models to estimate the average treatment effect of each treatment strategy on clinical outcomes. Completion of this proposal will fill knowledge gaps in current practice strategies as well as assess the risks and benefits of two classes of potential cardio- protective medications employed in management of patients with elevated serum troponin levels during sepsis. This work with inform my future application for a mentored Career Development Award geared toward randomized comparative effectiveness studies of potential cardio-protective medications with the goal of reducing cardiovascular complications following sepsis hospitalization. This proposal will serve as the foundation to my career as a leading physician-scientist in critical care health services and comparative effectiveness research with a focus on the management of the cardiovascular complications of non-cardiac critical illness.