Prospective Validation that Vulnerable Plaque Associated with Major Adverse Outcomes Have Larger Plaque Volume, Less Dense Calcium, and More Non-Calcified Plaque by Quantitative, Three-Dimensional Measurements Using Intravascular Ultrasound with Radiofrequency Backscatter Analysis
Results from the ATLANTA I Study
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Jesus G. Vazquez-Figueroa
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Sarah Rinehart
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Zhen Qian
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Parag H. Joshi
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Abhinav Sharma
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James Lee
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Hunt Anderson
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Laura Murrieta
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Charles Wilmer
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Harold Carlson
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Kenneth Taylor
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William Ballard
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Dimitri Karmpaliotis
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Anna Kalynych
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Charles Brown III
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Szilard Voros
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J. G. Vazquez-Figueroa (
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Work was conducted while at Piedmont Heart Institute
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) Integrated Cardiovascular Research Group
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Atlanta, GA, USA
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S. Voros Stony Brook University Medical Center
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NY, USA
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P. H. Joshi Johns Hopkins School of Medicine
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Baltimore, MD, USA
Whether quantitative, two-dimensional, and threedimensional plaque measurements by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) are different between intermediate lesions with or without major adverse cardiovascular events (MACE) is unknown. IVUS/VH-derived parameters were compared in 60 patients with an intermediate coronary lesion (40-70 %) between lesions that did or did not result in MACE over 12 months. IVUS/VH measurements were done at the site of the minimal lumen area (MLA) and on a per-plaque basis, defined by 40 % plaque burden. Prespecified, adjudicated MACE events occurred in 5 of 60 patients (8.3 %). MACE lesions had larger plaque burden (65 % vs. 53 %, p= 0.004), less dense calcium (6.6 % vs. 14.7 %, p = 0.05), and more non-calcified plaque, mostly fibrofatty kind (17.6 % vs. 10 %, p=0.02). Intermediate coronary lesions associated with MACE at 12 months have more plaque, less dense calcium, and more non-calcified plaque, particularly fibrofatty tissue by IVUS/VH.
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Atherosclerotic coronary artery disease (CAD) remains the
leading cause of morbidity and mortality in the USA, and
accordingly, approximately 1,350,000 patients suffer an
acute coronary syndrome (ACS) each year [1]. Moreover,
approximately 20 % of patients who suffered an initial event
will have a recurrent event within a year [2, 3].
Atherosclerosis progresses through a series of molecular
and cellular processes resulting in a series of geometrical and
compositional changes that can be detected by imaging
modalities [4]. The vulnerable plaque paradigm hypothesizes
that certain histopathological features of coronary
atherosclerotic plaques are associated with plaque rupture [5] and
include mildmoderate luminal stenosis, large plaque burden,
more lipid pool and lipid-rich necrotic core, more
inflammation, and less calcification. Moreover, thin-cap fibroatheromas
(TCFA) are the most predominant morphology found in
autopsy series of ruptured plaques [613]. However, prospective
validation of such features in vivo has been challenging in the
absence of a reliable imaging method.
Recently, gray-scale intravascular ultrasound (IVUS) and
IVUS with radiofrequency backscatter analysis (IVUS/VH)
have been utilized as an invasive means of visualizing human
coronary arterial plaques in vivo [14]. Several retrospective
IVUS/VH studies demonstrated that plaques associated with
events had larger plaque burden, more necrotic core, less
calcification, and the presence of IVUS/VH defined TCFA
(VH-TCFA) [15]. Furthermore, a recent, large, prospective
study (PROSPECT: A prospective natural-history study of
coronary atherosclerosis) utilizing three-vessel IVUS/VH
based on cross-sectional luminal analysis showed that
minimal lumen area (MLA) plaque burden and the presence of
VH-TCFA were independent predictors of major adverse
cardiovascular events (MACE) [16]. However, features of
nonobstructive plaques that resulted in MACE prospectively over
a 12-month period have not been investigated before in
threedimension (3D) on a per-plaque basis. Accordingly, we
hypothesized that plaques associated with MACE over a
12month period will have larger plaque burden, more
noncalcified plaque, more necrotic core, and less dense calcium
compared to lesions that were not associated with MACE,
based on 3D IVUS/VH measurements on a per-plaque basis.
General Study Design
The ATLANTA (Assessment of Tissue characteristics, Lesion
morphology and hemodynamics by Angiography with
fractional flow reserve, intravascular ultrasound and virtual histology
and Non-invasive computed Tomography in Atherosclerotic
plaques) study was a prospective, single-center,
investigatorinitiated study approved by the Institutional Review Board of
Piedmont Healthcare. The overall study design has been
published previously [15] and is shown in Fig. 1. Patients with
intermediate coronary arterial lesions who presented with signs
or symptoms suggestive of myocardial ischemia and who
qualified for the study based on enrollment criteria were included
either from the cardiac catheterization laboratory or from the
cardiovascular computed tomography laboratory. Main
inclusion criteria included the following: adults ages 1870, no
known or prior CAD, symptoms suggestive of myocardial
ischemia (...truncated)