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

Journal of Cardiovascular Translational Research, Jul 2013

Whether quantitative, two-dimensional, and three-dimensional 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. Pre-specified, 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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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 0 1 3 4 Jesus G. Vazquez-Figueroa 0 1 3 4 Sarah Rinehart 0 1 3 4 Zhen Qian 0 1 3 4 Parag H. Joshi 0 1 3 4 Abhinav Sharma 0 1 3 4 James Lee 0 1 3 4 Hunt Anderson 0 1 3 4 Laura Murrieta 0 1 3 4 Charles Wilmer 0 1 3 4 Harold Carlson 0 1 3 4 Kenneth Taylor 0 1 3 4 William Ballard 0 1 3 4 Dimitri Karmpaliotis 0 1 3 4 Anna Kalynych 0 1 3 4 Charles Brown III 0 1 3 4 Szilard Voros 0 1 3 4 0 J. G. Vazquez-Figueroa ( 1 Work was conducted while at Piedmont Heart Institute 2 ) Integrated Cardiovascular Research Group , Atlanta, GA, USA 3 S. Voros Stony Brook University Medical Center , Stony Brook, NY, USA 4 P. H. Joshi Johns Hopkins School of Medicine , 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. - 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)


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Jesus G. Vazquez-Figueroa, Sarah Rinehart, Zhen Qian, Parag H. Joshi, Abhinav Sharma, James Lee, Hunt Anderson, Laura Murrieta, Charles Wilmer, Harold Carlson, Kenneth Taylor, William Ballard, Dimitri Karmpaliotis, Anna Kalynych, Charles Brown III, Szilard Voros. 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, Journal of Cardiovascular Translational Research, 2013, pp. 762-771, Volume 6, Issue 5, DOI: 10.1007/s12265-013-9473-0