Article

Global Coronary Flow Reserve Is Associated With Adverse Cardiovascular Events Independently of Luminal Angiographic Severity and Modifies the Effect of Early Revascularization

Viviany R. TaquetiFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofRory HachamovitchFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofVenkatesh L. MurthyFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofMasanao NayaFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofCourtney FosterFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofJon HainerFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofSharmila DorbalaFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofRon BlanksteinFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions ofMarcelo F. Di CarliFrom the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (V.R.T., M.N., C.R.F., J.H., S.D., R.B., M.F.D.C.); Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH (R.H.); and Divisions of

2014en

ABI

Abstract

BACKGROUND: Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease (CAD), identifies patients at risk for cardiac death. We sought to determine the association between CFR, angiographic CAD, and cardiovascular outcomes. METHODS AND RESULTS: Consecutive patients (n=329) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography were followed (median 3.1 years) for cardiovascular death and heart failure admission. The extent and severity of angiographic disease were estimated with the use of the CAD prognostic index, and CFR was measured noninvasively by positron emission tomography. A modest inverse correlation was seen between CFR and CAD prognostic index (r=-0.26; P<0.0001). After adjustment for clinical risk score, ejection fraction, global ischemia, and early revascularization, CFR and CAD prognostic index were independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% confidence interval, 1.20-3.40; P=0.008; hazard ratio for 10-U increase in CAD prognostic index, 1.17; 95% confidence interval, 1.01-1.34; P=0.032). Subjects with low CFR experienced rates of events similar to those of subjects with high angiographic scores, and those with low CFR or high CAD prognostic index showed the highest risk of events (P=0.001). There was a significant interaction (P=0.039) between CFR and early revascularization by coronary artery bypass grafting, such that patients with low CFR who underwent coronary artery bypass grafting, but not percutaneous coronary intervention, experienced event rates comparable to those with preserved CFR, independently of revascularization. CONCLUSIONS: CFR was associated with outcomes independently of angiographic CAD and modified the effect of early revascularization. Diffuse atherosclerosis and associated microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact the outcomes of revascularization.

Identifiers

DOI: 10.1161/circulationaha.114.011939

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