Dr Brian Steffen

Coronary artery bypass graft surgery (CABG) is one of the most widely used cardiac procedures in the U.S., yet there is a considerable residual risk of developing postoperative complications (PoCs) and a relative dearth of studies that have aimed to elucidate their potential mechanisms. The long-term goal of this research is to reduce incident PoCs and improve outcomes among CABG patients by identifying mechanisms of PoC development and actionable targets for prophylaxis and patient monitoring. The objectives of the research are to identify components of the plasma proteome and their associated pathways that discriminate risk of PoCs and adverse post-discharge events in a multi-site prospective cohort of CABG patients. The central hypothesis is that plasma proteome components will discriminate risks of PoCs and post-hospital discharge outcomes that are independent of known risk factors and may further play causal roles in the development of these adverse outcomes.

This study's objectives will be accomplished by pursuing three specific aims:

• Identify preoperative plasma proteome liabilities that discriminate risk of: new-onset atrial fibrillation, acute kidney injury, renal failure, prolonged ventilation (>24 hrs), bleeding, reoperation, major adverse cardiovascular events, and death among CABG patients; near-term adverse outcomes up to 30 months following hospital discharge among CABG patients including any major adverse cardiovascular event, reoperation, all-cause hospital readmission, and all-cause mortality. Where feasible, enrichment analyses will identify associated pathways and networks, and a contingent Mendelian randomization analysis will be conducted to assess causality between proteins and the corresponding PoC or near-term event.
• Identify pre- to 2-day postoperative changes in the plasma proteome and associated pathways that discriminate risk of subsequent PoCs enumerated above, and serious adverse outcomes following hospital discharge (≤30 months).
• Identify the protein architecture that mediates associations between known PoC risk factors and corresponding PoC outcomes. Known PoC risk exposure variables will include preoperative body mass index, left ventricular ejection fraction, and dialysis treatment as well as operative blood product administration and cardiopulmonary bypass time.

This research is innovative because it will be the first prospective study conducted in a surgical cohort to identify proteomic signatures of PoCs and post-discharge outcomes, will identify associated pathways and networks of disease development, and will evaluate the potential causality of identified protein targets. It is significant because it will provide the requisite steps toward accelerating the precision medicine of cardiothoracic surgery and advancing prevention and patient monitoring at all operative stages. The knowledge gained with the execution of the above aims will offer critical insights for reducing these potentially debilitating and fatal conditions.