Impact of surgical revascularization strategy on left ventricular function, myocardial perfusion and clinical outcomes

Project Summary Coronary artery disease (CAD) is a leading cause of morbidity and mortality: revascularization via coronary artery bypass grafting (CABG) is a common therapy for CAD, which is performed via either single arterial graft (SAG) or multiple arterial grafting (MAG) strategies. Whereas arterial grafts have better long-term patency than vein grafts, data indicates that patients receiving MAG may experience higher perioperative risk. Cardiac function is known to predict prognosis after CABG, but the impact of different revascularization approaches on cardiac performance and consequences on clinical outcomes are incompletely understood. In this re- submission K23 proposal, I will build on my background in cardiothoracic anesthesia and advanced echo imaging to elucidate the effect of the two different revascularization strategies (SAG vs. MAG) on cardiac function immediately after CABG and subsequent clinical outcomes, in order to provide a framework for perioperative management of CABG patients. In Aim 1, I will examine the impact of CABG revascularization strategy on the change in cardiac function defined by echo strain. I will identify if MAG will result in lower cardiac performance as quantified by transesophageal echocardiography from baseline to after the operation. I will also evaluate whether the change echo strain will be associated with medications need to support hemodynamics. In Aim 2, I will determine the mechanism by which echo strain decreases after CABG. Myocardial perfusion on contrast-enhanced echo and flowmeter will be utilized to test the association with cardiac functional change (echo strain). I will also evaluate if MAG will result in lower myocardial perfusion than will SAG-based revascularization. In Aim 3, I will determine whether the decrease in echo strain predicts clinical outcomes at 6 months better than conventional imaging indices. By studying the link between revascularization techniques, cardiac function and physiology, I will lay the groundwork for a research career translating new insights regarding underlying mechanisms of cardiac dysfunction into meaningful anesthetic interventions that improve clinical outcomes. Under my strong mentorship team of Drs. Devereux (extensive expertise in cardiovascular imaging trials and cardiac outcomes research), Gaudino (internationally renowned cardiac surgeon with a focus on multi-arterial grafting and designing randomized clinical trials and m-PI of the funded parent trial ROMA), and Weinsaft (an expert in quantitative cardiac imaging and translational research), I will be able to enhance my clinical research skills while obtaining new technical skills advanced echocardiography and translational research that will allow me to become an independent investigator. In addition, new skills obtained from my K23 will directly guide the design of a planned R01 to (a) to assess LV response to vasoactive medications designed to improve arterial graft flow in CABG patients and (b) test vasodilator therapy to improve clinical outcomes in patients with MAG.