Noninvasive Detection of Subclinical
Coronary Atherosclerosis Coupled With
Assessment of Changes in Plaque Characteristics
Using Novel Invasive Imaging Modalities
The Integrated Biomarker and Imaging Study (IBIS)
Carlos A. G. Van Mieghem, MD,* Eugène P. McFadden, MBC
H
B, MD, FRCPI, FACC,*
Pim J. de Feyter, MD, P
H
D, FACC,* Nico Bruining, P
H
D,* Johannes A. Schaar, MD,*
Nico R. Mollet, MD,* Filippo Cademartiri, MD,* Dick Goedhart, MS
C
,† Sebastiaan de Winter, BS
C
,*
Gaston Rodriguez Granillo, MD,* Marco Valgimigli, MD,* Frits Mastik,* Anton F. van der Steen, P
H
D,*
Willem J. van der Giessen, MD, P
H
D,* Georgios Sianos, MD, P
H
D,* Bianca Backx, P
H
D,†
Marie-Angèle M. Morel, BS
C
,† Gerrit-Anne van Es, P
H
D,† Andrew Zalewski, MD, P
H
D,‡§
Patrick W. Serruys, MD, P
H
D, FACC*
Rotterdam, the Netherlands; and Philadelphia, Pennsylvania
OBJECTIVES Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and
to examine novel invasive modalities to describe prevalence and temporal changes in putative
characteristics of “high-risk” plaques.
BACKGROUND Conventional coronary imaging cannot identify “high-risk” lesions.
METHODS Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel
imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline
and 6 months later in 67 patients with diverse clinical presentations. Different imaging
techniques were compared within a common segment defined by multislice computed
tomography (MSCT).
RESULTS Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value
of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In
coronary arteries with Ͻ50% stenosis, there were no temporal changes in luminal and plaque
dimensions measured by quantitative coronary angiography or IVUS; however, a significant
reduction in abnormal strain pattern was detected on palpography (density high strain
spots/cm: 1.6 Ϯ 1.5 vs. 1.2 Ϯ 1.4, p ϭ 0.0123. These changes were mainly related to
significant changes in patients who presented with ST-segment elevation myocardial
infarction. The assessment of plaque echogenicity showed no temporal changes. There were
no correlations between circulating biomarkers and quantifiable imaging parameters.
CONCLUSIONS Mild angiographic disease is associated with large atherosclerotic plaques on MSCT.
Conventional invasive coronary imaging reveals static luminal and plaque dimensions on
standard medical therapy with plaque hypoechogenicity remaining unchanged over the
6-month period. By contrast, palpography measurements of strain correlate with clinical
presentation and significantly decrease on standard medical therapy. Novel imaging modal-
ities, such as palpography, might provide insights into plaque biology and might eventually
serve as intermediate end points in interventional trials. (J Am Coll Cardiol 2006;47:
1134–42) © 2006 by the American College of Cardiology Foundation
Atherosclerosis is a systemic disease in which the clinical
sequelae only weakly correlate with its extent or severity.
Furthermore, sudden death or acute coronary syndromes are
frequently the first manifestation of previously subclinical
atherosclerosis, and the majority of such events (i.e., 60% to
70%) occur as a result of plaque rupture at sites with noncritical
luminal narrowing (1–5). Pathologic studies have correlated
specific coronary plaque characteristics with fatal ischemic
events, but conventional imaging techniques, such as quan-
titative angiography and quantitative intravascular ultra-
sound (IVUS), cannot reliably identify high-risk, rupture-
prone, plaques prospectively (6). Thus, development of
novel coronary imaging modalities to detect structural and
compositional plaque characteristics has been the subject of
intensive preclinical and clinical research (7,8). In parallel
with the advances in novel invasive imaging, noninvasive
multislice computed tomographic angiography (MSCTA)
has matured to the extent that it can reliably identify
flow-limiting coronary lesions in relatively unselected
patients.
The aim of this study was four-fold: 1) to determine the
potential of MSCTA in the detection of subclinical, non-
From the *Erasmus Medical Center, Rotterdam, the Netherlands; †Cardialysis,
Rottterdam, the Netherlands; ‡GlaxoSmithKline, Philadelphia, Pennsylvania; and
§Thomas Jefferson University, Philadelphia, Pennsylvania. This study was supported
by a research grant from GlaxoSmithKline, Philadelphia, Pennsylvania.
Manuscript received June 12, 2005; revised manuscript received August 31, 2005,
accepted September 26, 2005.
Journal of the American College of Cardiology Vol. 47, No. 6, 2006
© 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2005.09.075