Fibrofatty Plaque Research Articles

Opalski’s syndrome: A rare variant of lateral medullary syndrome

Opalski’s syndrome: A rare variant of lateral medullary syndrome

Atherosclerosis: pathogenesis and pathology

Atherosclerosis and its clinical sequelae represent a huge and increasing global burden of morbidity and mortality in the form of coronary artery, peripheral vascular and cerebral vascular disease. The classical atherosclerotic lesion is an inflammatory fibrofatty plaque. Early notions of atherosclerosis were based on progressive calcification, however, atherosclerosis is now appreciated to be chronic and multifaceted, and the atherosclerotic plaque an “active biological environment.” The interplay of endothelial dysfunction, lipid accumulation, immune response, vascular smooth muscle cell migration, matrix turnover, and calcification is gradually being unravelled. Such insights are already leading to changes in diagnosis and management of patients with atherosclerosis. Serum biomarkers, non-invasive imaging, and genetic testing are being actively investigated for future clinical application. In this review, we provide an overview of pathological findings and the current understanding of the pathogenesis of atherosclerosis and offer some insights into the direction of atherosclerosis research.

Association of Coronary Wall Shear Stress With Atherosclerotic Plaque Burden, Composition, and Distribution in Patients With Coronary Artery Disease

BackgroundExtremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition.Methods and ResultsTwenty‐seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm2 increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS).ConclusionsIn patients with coronary artery disease: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.)

A virtual histology intravascular ultrasound analysis of coronary chronic total occlusions

We used virtual histology intravascular ultrasound (VH-IVUS) to investigate plaque composition of chronic total occlusions (CTO). There are limited data on the composition of CTOs, especially in vivo. VH-IVUS was performed in 50 CTO lesions (49 patients) after guidewire crossing or pre-dilation using a 1.5-2 mm balloon. Plaque composition in the proximal reference, distal reference, and CTO segment (subsequently divided into proximal, middle, and distal subsegments) was analyzed and reported as median and interquartile range. VH-IVUS phenotype was also assessed. The definition of a fibroatheroma was >10% confluent necrotic core (NC) in more than three consecutive frames. Overall, the maximum NC within the CTO [35.5% (28.7, 44.3%)] was similar to the proximal reference [35.6% (24.1, 42.1%)] and greater than the distal reference [31.5% (22.6, 35.2%), P < 0.01]. There was no difference in maximum NC observed among proximal [31.4% (25.2, 10.4%)], middle [31.0% (23.3, 38.3%)], and distal CTO subsegments [30.4% (22.0, 39.5%)]. Overall, 42/50 CTOs contained a VH-fibroathroma; and 8/50 did not. CTOs containing a VH-fibroatheroma had more NC and dense calcium while CTOs not containing a fibroatheroma had more fibrotic and fibrofatty plaque. Importantly, 60.5% of VH-fibroatheroma-containing CTOs had a thin-cap fibroatheroma (NC abutted to the lumen) in the proximal reference. Using VH-IVUS, CTO morphology can be divided into two patterns: (1) CTO with VH-fibroatheroma or (2) CTO without VH-fibroatheroma. This suggests two mechanisms of CTO formation-the majority evolving from acute coronary syndrome and thrombosis and the minority from atherosclerosis progression.

Impact of Diabetes Mellitus on Coronary Atherosclerosis and Plaque Composition Under Statin Therapy

Patients with diabetes mellitus (DM) have a markedly increased incidence of adverse cardiovascular events, but the mechanisms have not been well-characterized. The TRUTH study evaluated the effects of 8-month statin therapy on coronary artery plaque composition using virtual histology intravascular ultrasound (IVUS). Analyzable IVUS data were obtained from 119 patients, including 50 DM patients. The pattern of arterial remodeling, extent of coronary atherosclerosis, and plaque composition were compared in subjects with and without DM. Significant decreases in atheroma volume (-2.3%, P=0.02) and external elastic membrane volume (-1.7%, P=0.02) were observed only in the non-DM group. Although statin therapy significantly decreased the fibro-fatty component in both groups, this component at follow-up was significantly greater in the DM group (0.99 mm(3)/mm vs. 0.70 mm(3)/mm, P=0.03). Multivariate regression analysis showed that the presence of DM was associated with greater atheroma volume (β=0.203, P=0.02), particularly fibro-fatty plaque volume at follow-up (β=0.215, P=0.01). DM attenuated the degree of regression of coronary atherosclerosis under statin therapy. A large amount of fibro-fatty plaque volume under statin therapy may affect the development of coronary events in patients with DM.

Relation of Ruptured Plaque Culprit Lesion Phenotype and Outcomes in Patients With ST Elevation Acute Myocardial Infarction

We used virtual histology intravascular ultrasound (VH-IVUS) to assess culprit plaque rupture in 172 patients with ST-segment elevation acute myocardial infarction. VH-IVUS-defined thin-capped fibroatheroma (VH-TCFA) had necrotic core (NC) > 10% of plaque area, plaque burden > 40%, and NC in contact with the lumen for ≥ 3 image slices. Ruptured plaques were present in 72 patients, 61% of which were located in the proximal 30 mm of a coronary artery. Thirty-five were classified as VH-TCFA and 37 as non-VH-TCFA. Vessel size, lesion length, plaque burden, minimal lumen area, and frequency of positive remodeling were similar in VH-TCFA and non-VH-TCFA. However, the NC areas within the rupture sites of VH-TCFAs were larger compared to non-VH-TCFAs (p = 0.002), while fibrofatty plaque areas were larger in non-VH-TCFAs (p < 0.0001). Ruptured plaque cavity size was correlated with distal reference lumen area (r = 0.521, p = 0.00002), minimum lumen area (r = 0.595, p < 0.0001), and plaque area (r = 0.267, p = 0.033). Sensitivity and specificity curve analysis showed that a minimum lumen area of 3.5 mm2, a distal reference lumen area of 7.5 mm2, and a maximum NC area of 35% best predicted plaque rupture. Although VH-TCFA (35 of 72) was the most frequent phenotype of plaque rupture in ST-segment elevation myocardial infarction, plaque rupture also occurred in non-VH-TCFA: pathologic intimal thickening (8 of 72), thick-capped fibroatheroma (1 of 72), and fibrotic (14 of 72) and fibrocalcified (14 of 72) plaque. In conclusion, not all culprit plaque ruptures in patients with ST-segment elevation myocardial infarction occur as a result of TCFA rupture; a prominent fibrofatty plaque, especially in a proximal vessel, may be another form of vulnerable plaque. Further study should identify additional factors causing plaque rupture.

Abstract 9878: Pioglitazone Ameliorates Atherosclerotic Lesions with the Modification of the Balance of Effector and Regulatory T Cells in Apolipoprotein E Deficient Mice

BACKGROUND: Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ. Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels. PURPOSE: The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells. METHODS AND RESULTS: To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE-/-)mice were fed western diet and received PIO (20mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks (each n=12). Data showed that PIO markedly inhibited early fatty streak formation. Although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced by PIO. In general, macrophage expression in lesions was decreased by PIO. Additionally, the expression of Foxp3+ cells (regulatory T) was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4+interferon-γ+/CD4+interleukin-4+cell ratios were reduced. CONCLUSION: PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE-/- mice, which was associated with altering the balance of effector and regulatory T cells.

Tissue characterisation of atherosclerotic plaque in the left main: an in vivo intravascular ultrasound radiofrequency data analysis

To characterise plaque phenotypes in the left main stem (LMS) and the proximal left anterior descending (LAD) coronary artery using virtual histology assisted intravascular ultrasound (VH-IVUS). Patients with IVUS pullbacks including no less than the proximal 30 mm of the LAD and through the ostium of the left main were identified from a global IVUS registry. Plaque composition and phenotype frequency in the LMS and five consecutive non-overlapping 6 mm segments in the LAD were studied, resulting in six analysed segments per patient. There were 74 patients (72% male, mean age 65 years). The median LMS length was 5.4 mm (IQR 2.8-8.7 mm). The percent of fibrofatty plaque was greater in the LMS compared to the proximal LAD segments (27.9% [20.0-39.2] vs. 17.3% [12.2-23.1], p<0.001). Dense calcium and necrotic core content was less prevalent in the LMS compared to the LAD segments (2.5% [0.9-4.7] vs. 7.9% [4.1-12.3], p<0.001; and 8.0% [3.7-11.8] vs. 14% [9.2-17.9], p<0.001). The frequency of thin cap fibroatheroma (TCFA) was higher in the LAD compared with LMS (0% vs. 16.9% [4.9-34.5], p<0.001). Within the LAD, TCFA was most frequently observed in the second 6 mm segment, 12 mm from the ostium. TCFA was present more frequently in the proximal LAD than LMS, supporting the notion that plaque rupture occurs in non-uniform locations throughout the coronary tree and preferentially spares the LMS.

Atherosclerotic plaque composition assessed by virtual histology intravascular ultrasound and cerebral embolization after carotid stenting

Previous studies have investigated the predictive value of clinical and morphologic parameters for distal embolization during carotid interventions. The composition of the atherosclerotic plaque, using virtual histology intravascular ultrasound (VH-IVUS) imaging obtained with an IVUS catheter that is advanced through the lesion after a filter has been placed distally, has not been evaluated as a marker for cerebral embolization. The purpose of this study was to assess the relationship between atherosclerotic plaque composition determined with VH-IVUS and the occurrence of cerebral embolization after carotid artery stenting (CAS). During a 10-month period, 24 patients undergoing CAS procedures using a filter device for embolic protection were prospectively evaluated. All patients underwent VH-IVUS exams at the time of the intervention, transcranial Doppler (TCD) monitoring during CAS, and pre- and 24-hour postprocedural diffusion-weighted magnetic resonance imaging (DW-MRI) exams. Using VH-IVUS, plaque components were characterized as fibrotic, fibrofatty, dense calcium, and necrotic core. The frequency of Doppler-detected microembolic signals (MES) during CAS and the incidence and location of acute postprocedural embolic lesions detected with DW-MRI were assessed to determine cerebral embolization. Univariate and correlation analyses were used to assess the association between plaque composition and frequency of cerebral embolization. No periprocedural transient ischemic attacks, strokes, or deaths occurred within 30 days. Seventeen patients (71%) demonstrated new acute cerebral emboli in DW-MRI. Of these, all revealed ipsilateral lesions and 12 (50%) had contralateral lesions. For the entire study group, the median number of ipsilateral DW-MRI lesions was 1 (range, 0 to 3), and TCD MES counts were 227 (interquartile range, 143-315). Volumetric VH-IVUS analysis revealed that there was a trend for larger median dense calcium volume in patients with ipsilateral subclinical cerebral embolism detected with DW-MRI (33.2±24.5 mm3 vs 11.4±6.1 mm3; P=.08). Scatter plots of plaque components revealed statistically significant correlation between fibrofatty plaque volume (Spearman r=0.49; P=.016) and number of new ipsilateral lesions in DW-MRI. Degree of cerebral embolization during CAS measured with TCD correlated with plaque burden, necrotic core, fibrofatty, and fibrous volumes. Plaque composition, as determined by VH-IVUS, only weakly correlates with the degree of cerebral embolization after carotid stenting. Specifically, there is a trend for larger dense calcium volume in patients with distal embolization. Of note, the proportion of necrotic core, which has traditionally been considered the main component of a vulnerable or unstable plaque, is not definitely associated with subclinical cerebral embolization after CAS when a filter device for embolic protection is used. The role of VH-IVUS in evaluating plaque composition during CAS remains unestablished and warrants further investigation.

Atherosclerotic plaque components characterization and macrophage infiltration identification by intravascular ultrasound elastography based on b-mode analysis: validation in vivo

Intravascular ultrasound elastography (IVUSE) is a promising imaging technique for early investigation of vulnerable plaques. Compared to radiofrequency signal processing, digital B-mode analysis is simple and of higher portability. However, rare studies have been reported validating the latter technique in vivo. In this study, we developed an IVUSE computer software system involving semi-automatic border delineation and block-matching algorithm and validated the system in vivo. Seven minipigs were fed with atherogenic diet for 40weeks. For each pig, the endothelium of one side of the renal arteries was denuded at the fifth week. With cross-correlation analysis, Lagrangian strain was calculated from two intravascular ultrasound images acquired in situ. Sixty regions of interests were selected from 35 elastograms matched well with the corresponding histological slices. Plaque types within these regions were classified as fibrous, fibro-fatty or fatty on Masson's trichrome and Oil-red O staining. Macrophage infiltration was also evaluated with immunohistology. Comparison between the mean strain value of the region of interest and the histological results revealed significant differences in strain values among different plaque types and non-diseased artery walls. The extent of macrophage infiltration was found to be correlated positively with strain values. For identification of fibro-fatty and fibrous plaques and macrophage infiltration, the system showed high sensitivity (93, 96 and 92%, respectively) and specificity (89, 76 and 66%, respectively), as revealed by receiver operating characteristic analysis. Our IVUSE system based on B-mode analysis is capable of characterizing fibrous and fibro-fatty plaques and macrophage intensity, thus holds potential for identifying vulnerable plaque.

Plaque characteristics of nonobstructive coronary lesions in diabetic patients: an intravascular ultrasound virtual histology analysis

Patients with diabetes mellitus are known to be at increased risk for acute cardiovascular events. We used intravascular ultrasound virtual histology (IVUS-VH) to examine whether nonobstructive coronary artery lesions of diabetic patients have distinct plaque composition and morphology compared with nondiabetic patients. A total of 41 patients (13 diabetic and 28 nondiabetic) with proximally located angiographically nonobstructive coronary lesions were prospectively enrolled. In addition to plaque geometry, IVUS-VH lesion evaluation of the fibrous, fibro-fatty, necrotic core and calcified plaque components was performed. An IVUS-derived thin-cap fibroatheroma (IDTCFA) was defined as a lesion with a confluent necrotic core of at least 10% lumen cross-sectional area without evident overlying fibrous tissue and a plaque atheroma volume of at least 40% in at least three consecutive frames. Coronary artery lesions of diabetic and nondiabetic patients had similar plaque geometry. Lesions of diabetic patients were more likely to be positively remodeled than those of nondiabetic patients (67 vs. 27%, respectively, P = 0.02). Plaques of diabetic patients had significantly higher necrotic core percentages (23.3 +/- 6.1 vs. 17.1 +/- 8.7%, P = 0.03) and lower fibro-fatty tissue percentages (8 +/- 5 vs. 14.2 +/- 7.5%, P = 0.01) than those of nondiabetic patients. In addition, IDTCFAs were significantly more prevalent at the minimal lumen area site of diabetic patients compared to nondiabetic patients (92 vs. 54%, respectively, P = 0.02). After adjustment for various confounders, diabetes mellitus remained as the only independent clinical predictor of IDTCFAs at the minimal lumen area site [odds ratio (OR) 9.43, 95% confidence interval (CI) 1.06-84.04, P = 0.04]. Nonobstructive coronary artery lesions of diabetic patients have distinct compositional and morphological features, suggesting that these differences may explain the increased likelihood of coronary events in diabetic patients.

Effect of Statin on the Reference Segments after Bare-Metal Stent Implantation

Effect of Statin on the Reference Segments after Bare-Metal Stent Implantation

Relation of plaque size to compositions as determined by an in vivo volumetric intravascular ultrasound radiofrequency analysis

As the plaques have enlarged, the changes in specific plaque compositions have not been sufficiently investigated. We evaluated the relation of plaque size to each plaque component (fibrotic, fibrofatty, dense calcium, and necrotic core) in 244 patients with volumetric virtual histology intravascular ultrasound analysis. Plaque volume was significantly correlated with fibrotic volume (r = 0.886, P < 0.001), necrotic core volume (r = 0.716, P < 0.001), fibrofatty volume (r = 0.572, P < 0.001), and dense calcium volume (r = 0.382, P < 0.001). There was a weak correlation between plaque volume and percentage of fibrofatty plaque and dense calcium (r = 0.140, P = 0.030 and r = -0.146, P = 0.023, respectively). Plaque volume was not significantly correlated with percentage of fibrotic plaque and necrotic core. As the plaque volume increased, there was an increase in absolute amounts of each plaque component (fibrotic > necrotic core > fibrofatty > dense calcium). However, there were no significantly relevant correlations between plaque volume and percentage of each plaque component.

Pioglitazone modulates the balance of effector and regulatory T cells in apolipoprotein E deficient mice

Background and aims Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ (PPARγ). Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels. The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells. Methods and results To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE−/−) mice were fed western diet and received PIO (20 mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks. Data showed PIO markedly inhibited early fatty streak formation. Further, although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced. In general, macrophage expression in lesions was decreased. Additionally, the expression of Foxp3 + cells was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4 +IFN-γ +/CD4 +IL-4 + cell ratios were reduced. Conclusion PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE−/− mice, which was associated with altering the balance of effector and regulatory T cells.

Advances in Intravascular Imaging

Received March 25, 2009; accepted August 4, 2009. This review updates the role of various intravascular imaging techniques (1) in the detection of vulnerable plaque and (2) during percutaneous coronary intervention (PCI), especially drug-eluting stent (DES) implantation and follow-up—including intravascular ultrasound (IVUS), virtual histology (VH-IVUS) and integrated backscatter (IB-IVUS), optical coherent tomography (OCT), near-infrared (NIR) spectroscopy, angioscopy, and MRI. ### IVUS, IB-IVUS, and VH-IVUS The current intracoronary ultrasound imaging frequency range of 20 to 45 MHz provides 70 to 200 μm axial resolution with >5 mm penetration.1,2 Grayscale IVUS allows robust quantitative measurements including lumen, vessel, and plaque area; qualitative assessment of lesions preintervention; and quantitative assessment and complications of lesions postintervention; however, it has poor sensitivity for detecting lipid-rich plaque (67%).3 High-frequency IVUS transducers can produce better resolution that should also improve plaque characterization but at the trade off of greater ultrasound reflection from blood. Blood speckle with >40 MHz ultrasound can cause confusion when identifying the lumen-tissue border, detecting in-stent neointimal tissue, etc; but it is easily solved by saline (negative contrast) injection through the guiding catheter.4 Standard grayscale IVUS is limited, in part, because it uses only reflected ultrasound amplitude to formulate the image and requires significant postprocessing. In an effort to improve on the qualitative assessment of the reflected ultrasound signal, Kawasaki et al developed a plaque characterization algorithm called IB-IVUS using time domain information directly from the radiofrequency signal. This process has resulted in improved plaque characterization with a reported in vitro sensitivity of 90% and specificity or 92% for lipid-rich plaque.5,6 In a similar effort to improve plaque characterization, spectral analysis (VH-IVUS) combined frequency and amplitude analysis and used an algorithm developed from known tissue types to detect fibrous plaque, fibrofatty plaque, necrotic core (NC), and dense calcium (Figure 1A′, 1B′). Reported sensitivity and …

Effects of Statin Treatments on Coronary Plaques Assessed by Volumetric Virtual Histology Intravascular Ultrasound Analysis

We evaluated the effects of statin treatments for each component of coronary plaques. Effects of statin treatments on coronary plaques have not been sufficiently evaluated. One hundred patients without significant lesion stenosis underwent baseline and 12-month follow-up virtual histology (VH) intravascular ultrasound (IVUS) studies and were treated with statin for 1 year. They were randomized to simvastatin (20 mg/day, n = 50) or rosuvastatin (10 mg/day, n = 50). With VH-IVUS, plaque was characterized as fibrotic, fibrofatty, dense calcium, and necrotic core. In overall patients, necrotic core volume significantly reduced (15.7 to 13.7 mm(3), p = 0.010) and fibrofatty plaque volume increased (4.3 to 5.5 mm(3), p = 0.006) after statin treatments for 1 year. There were no significant differences of changes in either plaque component volume between simvastatin- and rosuvastatin-treated subgroups. In serial comparisons during 1-year follow-up, simvastatin treatment did not achieve statistically significant changes in fibrofatty plaque (4.1 to 5.1 mm(3), p = 0.131) and necrotic core volume (15.8 to 14.4 mm(3), p = 0.216). However, there was a significant decrease in necrotic core volume (15.5 to 13.0 mm(3), p = 0.015) and an increase in fibrofatty plaque volume (4.5 to 5.9 mm(3), p = 0.017) in the rosuvastatin-treated subgroup. Serial volumetric VH-IVUS analysis showed that statin treatments might be associated with significant changes in necrotic core and fibrofatty plaque volume in overall patients. The changes in both plaques' component volume were not statistically different between simvastatin- and rosuvastatin-treated subgroup.

Relation Between Individual Plaque Components and Overall Plaque Burden in the Prospective, Multicenter Virtual Histology Intravascular Ultrasound Registry

The impact of total plaque burden on absolute and relative amounts of each virtual histologic (VH) intravascular ultrasound (IVUS) plaque component has yet to be studied. We analyzed gray-scale and VH-IVUS findings in the first 990 patients enrolled in the 3,000+ patient global VH-IVUS registry. Whole pullback plaque burden and absolute and relative cross-sectional areas of fibrous tissue, fibrofatty plaque, dense calcium, and necrotic core were analyzed using a linear regression statistical model. Overall, absolute cross-sectional areas of each of the 4 plaque components correlated with total plaque cross-sectional area; however, the correlation between fibrous tissue and total plaque cross-sectional area was stronger than the correlation between fibrofatty plaque, dense calcium, or necrotic core and total plaque cross-sectional area. This was also true overall for each of the subgroups analyzed (gender, age, and presence/absence of acute coronary syndromes). Slope of the regression line relating each plaque component to overall plaque mass showed that 50% of the plaque cross-sectional area increase was because of fibrous tissue with a more gradual increase in fibrofatty plaque, dense calcium, and necrotic core. However, when comparing relative amounts of each plaque component with total plaque cross-sectional area, there was no significant relation between the increase in fibrous tissue, fibrofatty plaque, dense calcium, and necrotic core and the increase in total plaque cross-sectional area. In conclusion, only the absolute area of each plaque component correlated to overall plaque area, not the relative amount of each plaque; therefore, VH-IVUS plaque component increases must be analyzed by controlling for increases in plaque mass.

Inflammatory Burden of Cardiac Allograft Coronary Atherosclerotic Plaque Is Associated With Early Recurrent Cellular Rejection and Predicts a Higher Risk of Vasculopathy Progression

This study was designed to investigate tissue characterization of the coronary allograft atherosclerotic plaque with virtual histology intravascular ultrasound (VH-IVUS) imaging to assess the presence and predictors of vessel wall inflammation and its significance in cardiac allograft vasculopathy (CAV) progression. A unique form of accelerated atherosclerosis, CAV remains the leading cause of late morbidity and mortality in heart transplant patients. The pathogenesis of CAV is not fully elucidated. A total of 86 patients with coronary allograft vasculopathy underwent VH-IVUS examination of the left anterior descending coronary artery 3.61 +/- 3.04 years following cardiac transplantation. Based on the VH-IVUS plaque characteristics, coronary allograft plaque was divided on virtual histology intravascular ultrasound-derived "inflammatory" (VHD-IP) (necrotic core and dense calcium > or =30%) and "noninflammatory" plaque (VHD-NIP) (necrotic core and dense calcium <30%). Total rejection scores were calculated based on the 2004 International Society of Heart and Lung Transplantation rejection grading system. In the whole study population, the mean percentage of fibrous, fibrofatty, dense calcified, and necrotic core plaques in a mean length of 62.3 +/- 17.4 mm of the left anterior descending coronary artery were 50 +/- 17%, 16 +/- 11%, 15 +/- 11%, and 18 +/- 9%, respectively. Patients with a 6-month total rejection score >0.3 had significantly higher incidence of VHD-IP than those with a 6-month total rejection score < or =0.3 (69% vs. 33%, p = 0.011). The presence of VHD-IP at baseline was associated with a significant increase in plaque volume (2.42 +/- 1.78 mm(3)/mm vs. -0.11 +/- 1.65 mm(3)/mm, p = 0.010), plaque index (7 +/- 9% vs. 0 +/- 8%, p = 0.04), and remodeling index (1.24 +/- 0.44 vs. 1.09 +/- 0.36, p = 0.030) during 12 months of follow-up when compared with the presence of VHD-NIP at baseline and during follow-up. The presence of VHD-IP as assessed by VH-IVUS is associated with early recurrent rejection and with higher subsequent progression of CAV. A VH-IVUS assessment may add important information in the evaluation of transplant recipients.

The potential of RF backscattered IVUS data and multidetector-row computed tomography images for tissue characterization of human coronary atherosclerotic plaques

The aim is to compare virtual histology which uses spectral analysis of backscattered intravascular ultrasound (VH-IVUS) and multidetector-row computed tomography (MDCT) for the characterization of coronary atherosclerotic plaques obtained by directional coronary atherectomy (DCA). We performed DCA in 15 de novo native coronary stenotic lesions (15 patients) and selected one or two segments within the plaque from each patient (total 29 segments). Then, we evaluated the accuracy of the VH-IVUS findings in 50 sites among the 29 segments compared with the histopathology findings. MDCT was performed in all patients before percutaneous coronary intervention (PCI), and CT density values were measured. VH-IVUS data analysis correlated well with histopathological examination (predictive accuracy: 66.7% for fibrous, 100% for fibro-fatty, 100% for necrotic core, and 100% for dense calcium regions, respectively). In addition, CT density values between fibrous and fibro-fatty plaques classified by histopathology were 100.0 +/- 26.0 HU versus 110.4 +/- 67.9 HU, there were no difference among them (P = 0.594). These findings indicated that the validation of plaque characteristics using VH-IVUS correlates well with histopathology. While tissue characterization using CT density could be difficult to distinguish between fibro-fatty and fibrous tissue.

Progression and Observational Frequency of Atheromatous Plaques in Autopsied Coronary Arteries

Background and ObjectivesVirtual histology-intravascular ultrasound (VH-IVUS) studies on early-stage fibroatheroma, the probable precursor lesion of progression to thin-cap fibroatheroma (TCFA), have only rarely been done in man. We investigated the progression and observational frequency of fibroatheromas, and compared plaque components between early-stage and advance-staged fibroatheromas in the general population.Subjects and MethodsWe assessed coronary fibroatheromas using VH-IVUS and histopathologic analysis of 109 coronary lesions from 40 autopsied cases that were not due to sudden cardiac death (NSCD cases). Fibroatheromas were grouped into early fibroatheroma, late fibroatheroma, thick-cap fibroatheroma (TkCFA), and thin-cap fibroatheroma.ResultsMean patient age was 45±11 years old and 71% were males. Of 109 lesions, 27% were early fibroatheromas, 53% late fibroatheromas, 9% TkCFA, and 11% TCFA. VH-IVUS showed that there was relatively less fibrotic and fibrofatty plaque and more dense calcium deposits as fibroatheromas progressed. Furthermore, the relative amounts of fibrotic and fibrofatty plaque decreased (r=0.773, p<0.001 and r=0.538, p<0.001, respectively) as the necrotic core increased, while the relative area of dense calcium increased (r=0.665, p<0.001) as the size of the necrotic core increased.ConclusionOf NSCD cases in Korea, 27% were early fibroatheromas, 53% were late fibroatheromas, 9% were TkCFA, and 11% were TCFA. Advance-staged fibroatheromas show more necrotic core volume and more dense calcium than small, early-stage fibroatheromas.