DESCRIPTION (provided by applicant): One of the most devastating complications of coronary artery bypass surgery (CABG) is postoperative stroke. While the etiology of stroke after CABG is multifactorial, atheroemboli generated during aortic manipulation is believed to account for most cerebral embolic events. Manipulation of the aorta during CABG occurs during aortic cannulation, institution and maintenance of cardiopulmonary bypass, and during aortic clamping and unclamping with either a cross-clamp, partial-occluding clamp, or both. One operative strategy to minimize aortic manipulation is to avoid cardiopulmonary bypass altogether by using off-pump techniques (OPCAB). Another method is to avoid the use of aortic clamps and to construct proximal aortocoronary anastomoses with facilitating devices that do not require aortic clamping. The effect of these strategies on reducing cerebral embolic events and the underlying mechanism for this reduction are not well-defined. This study will test the hypothesis that an off-pump (OPCAB) approach and facilitating devices to perform clampless proximal anastomoses will result in the least amount of aortic manipulation and therefore the lowest incidence and frequency of cerebral embolic events. The approach associated with the lowest incidence of TCD-detected cerebral embolic events will also result in the lowest incidence and severity of postoperative neurocognitive decline. Transcranial Doppler ultrasonography is an established method to detect cerebral embolic signals during cardiac surgery and will be utilized to detect cerebral embolic events during the operation. After an on- or off-pump strategy is selected, patients will be subsequently randomized to one of two clamping strategies. There will be 4 groups of patients: 1) OPCAB patients randomized to no clamping (facilitating device); 2) OPCAB patients randomized to partial clamping; 3) on-pump patients randomized to double clamping; and 4) on-pump patients randomized to a single clamp strategy. As part of the "Mentored Patient-Oriented Research Career Development Award" I will enroll in and complete an established, formal didactic curriculum leading to a Master of Science Degree in Clinical Research. This is an NIH-sponsored (NIH K30 CTSA) joint program offered by the Graduate School of Arts and Sciences at Emory University and the Atlanta Clinical and Translational Research Institute. This training will provide defined credentials and a body of knowledge which will provide me with the necessary skills to pursue a career in clinical research investigation. Mentorship will be provided during weekly meetings with the Division of Cardiothoracic Surgery's Clinical Research Unit, directed by my mentor, John D. Puskas, MD, as well as regularly scheduled meetings with my co-mentors and other members of the mentoring team. I will receive the appropriate training and supervision necessary to become an independent investigator conducting patient-centered clinical research. This has been my firm career goal since the start of my training in cardiothoracic surgery; I am committed to achieving this goal.

Project Narrative The proposed research plan has a high probability of significantly impacting public health by providing surgeons clear guidance in choosing surgical techniques that will reduce the incidence of cerebral embolic events during coronary artery bypass surgery. These techniques, including the use of off-pump techniques and clampless anastomotic devices are all presently available to surgeons nationwide, but are infrequently utilized due to lack of compelling comparative effectiveness studies. More commonly, other strategies that result in a higher incidence of aortic manipulation are used during coronary artery bypass surgery.