Coronarybypassgraftsurgery(CABG)improvesthelivesofpatientswithcoronarydisease(CAD)asagroup, but20%ofpatientsremainsymptomaticoneyearaftersurgery.InclinicalpracticeCABGdecisionsarelargely drivenbystenosisseveritydeterminedfrominvasiveangiographydespitetheknownrelevanceoffunctional CAD parameters. This practical impasse will continue to exist without clinically available, high-resolution, quantitativefunctionalimaging,andabetterunderstandingoftheclinicaloutcomesinrelationtoanatomical (angiography) and functional (ischemia, scar tissue) factors. The long-term goal is to improve outcome of CABG through personalized imaging-guided care. The overall objective of this proposal is to identify determinants of myocardial flow restoration (ischemia reduction), and develop integrated imaging tools for individualized, lesion-specific CABG decision-making, and computational flow simulations based on the patient?s anatomy and function to predict the hemodynamic outcome. Supported by studies using invasive FFR-guided CABG, the rationale for the proposed research is that integration of anatomical (angiography) andfunctionalinformation(ischemia,scartissue)willidentifyindividualcoronaryvesselsthatwillbenefitfrom revascularization,andindividualoptimizationofsurgicalproceduresbyflowsimulationswillmaximizeclinical benefit of CABG for patients with CAD. Supported by promising preliminary data, three specific aims are proposed: 1) Prospectively identify angiographic, functional and clinical baseline determinants of outcome afterCABG,definedasimprovementofmyocardialperfusion(ischemiareduction)andanginasymptoms;?2) Develop and validate a comprehensive imaging strategy and clinically applicable tool that integrate high- resolution angiographic and quantitative functional information (ischemia, viability) for per-vessel/lesion revascularization decisions;? 3) Develop and validate new multi-parametric computational flow simulations, withincorporationoffunctionalimagingdata,whichallowsforpredictionofindividualhemodynamicoutcome and ultimately surgical optimization based on virtual hemodynamic results. This approach is innovative because new imaging techniques will advance the field?s understanding of CABG physiology, and new clinicallyapplicabletoolswillbedevelopedforcomprehensiveclinicaldecision-makingandoptimizedsurgical planning.Theacquiredknowledgeanddevelopedtoolsareapplicabletoothervascularcontexts,andmay also be instrumental for new therapeutic innovations. The proposed research is significant because identification of CABG outcome determinants, and new solutions for comprehensive decision-making and procedural guidance, have the potential to improve the effectiveness (by complete functional revascularization) and efficiency of CABG (by avoiding futile grafts). For a large group of patients, these innovations willimprove thepatient-valued benefit of CABG(complications,symptoms), andalsodecrease costbyimprovedefficiencyofcare.
TheproposedresearchisrelevanttothepublichealthbecauseidentificationofCABGoutcomedeterminants, and development of diagnostic solutions for comprehensive decision-making and procedural guidance of CABG surgery, can help achieve complete functional revascularization and restoration of myocardial blood flow in more patients. Thus, the proposed research is relevant to the NIH?s mission that pertains to the discoveryoffundamentalknowledgeaboutthenatureandbehavioroflivingsystemsandtheapplicationof thatknowledgetoenhancehealth,lengthenlife,andreduceillnessanddisability.