Near-Infrared Spectroscopy Enhances Intravascular Ultrasound Assessment of Vulnerable Coronary Plaque: A Combined Pathological and In Vivo Study.
OBJECTIVE
Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries.


RESULTS
Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo.


CONCLUSIONS
Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma.
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Rishi
R
Puri
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Ryan D
RD
Madder
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Sean P
SP
Madden
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Stephen T
ST
Sum
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Kathy
K
Wolski
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
James E
JE
Muller
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Jordan
J
Andrews
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Karilane L
KL
King
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Yu
Y
Kataoka
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Kiyoko
K
Uno
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Samir R
SR
Kapadia
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
E Murat
EM
Tuzcu
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Steven E
SE
Nissen
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Renu
R
Virmani
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Akiko
A
Maehara
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.).
Gary S
GS
Mintz
From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., K.W., K.L.K., K.U., S.E.N.), and Department of Cardiovascular Medicine (R.P., S.R.K., E.M.T., S.E.N.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, South Australia (R.P., S.J.N.); Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI (R.D.M.); InfraRedX Inc., Burlington, MA (S.P.M., S.T.S., J.E.M.); South Australian Health and Medical Research Institute, Adelaide, South Australia (J.A., Y.K., S.J.N.); CVPath Institute, Gaithersburg, MD (R.V.); and Cardiovascular Research Foundation, New York, NY (A.M., G.S.M.). stephen.nicholls@sahmri.com.
Stephen J
SJ
Nicholls
D000368:Aged; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011379:Prognosis; D019265:Spectroscopy, Near-Infrared; D018084:Ultrasonography, Interventional; D066253:Vascular Remodeling
D015415:Biomarkers; D008055:Lipids
artherosclerotic plaque; coronary artery disease; intravascular imaging; remodeling; vulnerable plaque