Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization.
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.


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.
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Viviany R
VR
Taqueti
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Rory
R
Hachamovitch
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Venkatesh L
VL
Murthy
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Masanao
M
Naya
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Courtney R
CR
Foster
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Jon
J
Hainer
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Sharmila
S
Dorbala
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
Ron
R
Blankstein
From 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 Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.). mdicarli@partners.org.
Marcelo F
MF
Di Carli
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000503:physiopathology / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D062645:Percutaneous Coronary Intervention; D049268:Positron-Emission Tomography; D011379:Prognosis; D012039:Regional Blood Flow / Q000502:physiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
angiography; coronary artery disease; ischemia; positron emission tomography; revascularization