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CLINICAL RESEARCH: ATHEROSCLEROSIS

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, MBChB, MD, FRCPI, FACC^_*, Pim J. de Feyter, MD, PhD, FACC^_*, Nico Bruining, PhD^_*, Johannes A. Schaar, MD^_*, Nico R. Mollet, MD^_*, Filippo Cademartiri, MD^_*, Dick Goedhart, MSc, Sebastiaan de Winter, BSc^_*, Gaston Rodriguez Granillo, MD^_*, Marco Valgimigli, MD^_*, Frits Mastik^_*, Anton F. van der Steen, PhD^_*, Willem J. van der Giessen, MD, PhD^_*, Georgios Sianos, MD, PhD^_*, Bianca Backx, PhD, Marie-Angèle M. Morel, BSc, Gerrit-Anne van Es, PhD, Andrew Zalewski, MD, PhD^, and Patrick W. Serruys, MD, PhD, FACC^_*,_*

^_* Erasmus Medical Center, Rotterdam, the Netherlands
Cardialysis, Rottterdam, the Netherlands
GlaxoSmithKline, Philadelphia, Pennsylvania
Thomas Jefferson University, Philadelphia, Pennsylvania.

Manuscript received June 12, 2005; revised manuscript received August 31, 2005, accepted September 26, 2005.

^_* Reprint requests and correspondence: Dr. Patrick W. Serruys, Thorax Center, Room Ba 583, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. (Email: p.w.j.c.serruys{at}erasmusmc.nl).

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 <50% 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 ± 1.5 vs. 1.2 ± 1.4, p = 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 modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.

Abbreviations and Acronyms   EEM = external elastic membrane   HDL-C = high-density lipoprotein cholesterol   IBIS = Integrated Biomarker and Imaging Study   IVUS = intravascular ultrasound   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   MSCT = multislice computed tomography   MSCTA = multislice computed tomographic angiography   PCI = percutaneous coronary intervention   PV = plaque volume   ROC = ROtterdam Classification   ROI = region of interest   STEMI = ST-segment elevation myocardial infarction

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