Prospective, head-to-head comparison of quantitative coronary angiography, quantitative computed tomography angiography, and intravascular ultrasound for the prediction of hemodynamic significance in intermediate and severe lesions, using fractional flow reserve as reference standard (from the ATLANTA I and II Study).

The objective of this study was to compare the diagnostic accuracy of quantitative coronary angiography (QCA), coronary computed tomography angiography (CTA), and intravascular ultrasound (IVUS) with fractional flow reserve (FFR) measurements. Eighty-five lesions (40% to 99% diameter stenosis) in 85 patients were prospectively interrogated by QCA, CTA, IVUS, and FFR. Minimal lumen diameter (MLD), percent diameter stenosis (%DS), minimal lumen area (MLA), and percent area stenosis (%AS) were measured. Correlation, receiver operating characteristic analysis, kappa statistics, and multivariable logistic regression was used to assess relation between anatomic measurements and FFR. Average age was 61.3 ± 7.8; 62% were men. QCA-derived mean %DS was 55.3% ± 19.5%; mean FFR 0.81 ± 0.17; 27% had FFR ≤0.75. QCA had the strongest correlation, followed by CTA and then IVUS for MLD (r = 0.67, 0.47, and 0.29, respectively) and for %DS (r = -0.63, -0.52, and -0.22, respectively); QCA-derived MLD had area under the curve of 0.96, with 95% sensitivity and 82% specificity. Cut-point, area under the curve, sensitivity, and specificity for CTA-MLA and IVUS-MLA were 3.11 mm(2), 0.86, 81%, and 81% and 2.68 mm(2), 0.75, 70%, and 80%. In multivariable analysis for each modality, MLD on QCA (odds ratio [OR]: 0.002), %AS on CTA (OR: 1.09) and MLA on IVUS (OR: 0.28) remained independent predictors. In conclusion, in intermediate-to-severe lesions, QCA-, CTA-, and IVUS-derived quantitative anatomic measurements correlated with FFR. CTA-derived cut-points were similar to respective measurements on QCA and IVUS and had similar or better diagnostic performance compared with IVUS.

Apoprotein B, small-dense LDL and impaired HDL remodeling is associated with larger plaque burden and more noncalcified plaque as assessed by coronary CT angiography and intravascular ultrasound with radiofrequency backscatter: results from the ATLANTA I study.

BACKGROUND: Apoprotein B-containing lipoproteins are atherogenic, but atheroprotective functions of apoprotein A-containing high-density lipoprotein (HDL) particles are poorly understood. The association between lipoproteins and plaque components by coronary computed tomography angiography (CTA) and intravascular ultrasound with radiofrequency backscatter (IVUS/VH) has not been evaluated. METHODS AND RESULTS: Quantitative, 3-dimensional plaque measurements were performed in 60 patients with CTA and IVUS/VH. Apoproteins, lipids, and HDL subpopulations were measured with 2-dimensional (2D) gel electrophoresis, and correlation was assessed with univariate and multivariable models. ApoB particles were associated with a higher proportion of noncalcified plaque (NCP) and a lower proportion of calcified plaque (small, dense low-density lipoprotein cholesterol and high-density NCP: r=0.3, P=0.03; triglycerides and low-density NCP: r=0.34, P=0.01). Smaller, dense, lipid-poor HDL particles were associated with a shift from calcified plaque to NCP on CTA (α3-HDL% and low-density NCP: r=0.32, P=0.02) and with larger plaque volume on IVUS/VH (α4-HDL%: r=0.41, P=0.01; α3-HDL%: r=0.37, P=0.03), because of larger dense calcium (α4-HDL%: r=0.37, P=0.03), larger fibrous tissue (α4-HDL%: r=0.34, P=0.04), and larger necrotic core (α4-HDL%: r=0.46, P<0.01; α3-HDL%: r=0.37, P=0.03). Larger lipid-rich HDL particles were associated with less low-density NCP on CTA (α2-HDL%: r=-0.34, P=0.02; α1-HDL%: r=-0.28, P=0.05), with smaller plaque volume on IVUS/VH (pre-α2-HDL: r=-0.33, P=0.05; α1-HDL%: r=-0.41, P=0.01; pre-α2-HDL: r=-0.33, P=0.05) and with less necrotic core (α1-HDL: r=-0.42, P<0.01; pre-α2-HDL: r=-0.38, P=0.02; α2-HDL: r=-0.35, P=0.03; pre-α1-HDL: r=-0.34, P=0.04). Pre-ß2-HDL was associated with less calcification and less stenosis by both modalities. CONCLUSIONS: ApoB and small HDL particles are associated with larger plaque burden and more noncalcified plaque, whereas larger HDL and pre-ß2-HDL particles are associated with plaque burden and less noncalcified plaque by both CTA and IVUS/VH.

A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study.

BACKGROUND: A composite, peripheral gene expression score based on quantitative RNA-measurements has been validated for detecting stenosis against invasive coronary X-ray angiography. IVUS/VH has been validated for quantitative measurements of coronary plaque volume and composition and has been shown to be predictive of outcomes and treatment effects. The correlation between peripheral gene expression and coronary plaque composition by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) is unknown. METHODS: Peripheral blood gene expression score (GES) was prospectively measured in 18 patients undergoing IVUS/VH. Plaque volume and composition [fibrous tissue (FI), fibro-fatty tissue (FF), necrotic core (NC) and dense calcium (DC)] were quantified in 3 dimensions in all plaques within the entire pullback. The relationship to GES was assessed by Spearman rank correlation. RESULTS: Mean age was 61.1±8.6 years; 67% were male. 1,158 mm of coronary anatomy was imaged by IVUS/VH. Using a validated scale of 1-40, mean GES was 21.6±9.4. GES was associated with plaque volume (R(2)=0.55; P=0.018), NC volume (R(2)=0.56; P=0.015), DC volume (R(2)=0.60; P=0.007), and non-calcified plaque volume (R(2)=0.50; P=0.036) by Spearman rank correlation. CONCLUSIONS: In this preliminary report, increased GES was associated with higher plaque volume and a more vulnerable plaque phenotype as evidenced by NC and DC. This composite GES is not only associated with obstructive coronary disease, but also with higher plaque volume and vulnerable phenotype.

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.

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.

Prospective validation of standardized, 3-dimensional, quantitative coronary computed tomographic plaque measurements using radiofrequency backscatter intravascular ultrasound as reference standard in intermediate coronary arterial lesions: results from the ATLANTA (assessment of tissue characteristics, lesion morphology, and hemodynamics by angiography with fractional flow reserve, intravascular ultrasound and virtual histology, and noninvasive computed tomography in atherosclerotic plaques) I study.

OBJECTIVES: This study sought to determine the accuracy of 3-dimensional, quantitative measurements of coronary plaque by computed tomography angiography (CTA) against intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH). BACKGROUND: Quantitative, 3-dimensional coronary CTA plaque measurements have not been validated against IVUS/VH. METHODS: Sixty patients in a prospective study underwent coronary X-ray angiography, IVUS/VH, and coronary CTA. Plaque geometry and composition was quantified after spatial coregistration on segmental and slice-by-slice bases. Correlation, mean difference, and limits of agreement were determined. RESULTS: There was significant correlation for all pre-specified parameters by segmental and slice-by-slice analyses (r = 0.41 to 0.84; all p < 0.001). On a segmental basis, CTA underestimated minimal lumen diameter by 21% and overestimated diameter stenosis by 39%. Minimal lumen area was overestimated on CTA by 27% but area stenosis was only underestimated by 5%. Mean difference in noncalcified plaque volume and percent and calcified plaque volume and percent were 38%, -22%, 104%, and 64%. On a slice-by-slice basis, lumen, vessel, noncalcified-, and calcified-plaque areas were overestimated on CTA by 22%, 19%, 44%, and 88%. There was significant correlation for percentage of atheroma volume (0.52 vs. 0.54; r = 0.51; p < 0.001). Compositional analysis suggested that high-density noncalcified plaque on CTA best correlated with fibrous tissue and low-density noncalcified plaque correlated with necrotic core plus fibrofatty tissue by IVUS/VH. CONCLUSIONS: This is the first validation that standardized, 3-dimensional, quantitative measurements of coronary plaque correlate with IVUS/VH. Mean differences are small, whereas limits of agreement are wide. Low-density noncalcified plaque correlates with necrotic core plus fibrofatty tissue on IVUS/VH.

Quantitative measurements of coronary arterial stenosis, plaque geometry, and composition are highly reproducible with a standardized coronary arterial computed tomographic approach in high-quality CT datasets.

BACKGROUND: Computed tomographic (CT) coronary angiography provides a noninvasive method for coronary plaque detection and quantification, but data are limited on reproducibility of a quantitative evaluation. METHODS: Intrarater and interrater reliability of a semiquantitative and highly standardized, fully quantitative approach was evaluated in 480 coronary segments in 30 patients. Quantitative vessel-wall and plaque geometrical parameters (minimal lumen diameter [MLD], minimal lumen area [MLA], percentage of atheroma volume [PAV], and remodeling index [RI]) and compositional parameters (calcified plaque volume [CAP] and % of CAP [%CAP], noncalcified plaque [NCP] and % of NCP [%NCP], high-density NCP volume [HD-NCP] and % of HD-NCP [%HD-NCP] and low-density NCP volume [LD-NCP] and % of LD-NCP [%LD-NCP]) were measured. Semiquantitative agreement was evaluated by weighted κ; quantitative agreement was evaluated by concordance correlation coefficient (CCC) and Bland-Altman analysis. RESULTS: Intraobserver agreement for MLD, MLA, and RI was excellent (CCC: 0.96, 0.96, and 0.84, respectively). Intraobserver agreement for %CAP, %HD-NCP, and %LD-NCP was also excellent (CCC: 0.99, 0.98,and 0.96, respectively). Interobserver agreement for MLD, MLA, PAV and RI was excellent (CCC: 0.98, 0.99, 0.96,and 0.86, respectively). Interobserver agreement for %CAP, % NCP, %HD-NCP, and %LD-NCP was also excellent (CCC: 0.99, 0.99, 0.98,and 0.90, respectively), and mean differences were small. Quantitative analysis showed statistically significant differences in both geometrical and compositional parameters between normal segments and those with plaque. CONCLUSIONS: Standardized, quantitative analysis of coronary CTA datasets is reproducible for the measurement of plaque geometrical and compositional parameters and can quantify differences between normal and abnormal segments in high-quality datasets.

Cardiovascular computed tomographic assessment of the effect of combination lipoprotein therapy on coronary arterial plaque: rationale and design of the AFRICA (Atorvastatin plus Fenofibric acid in the Reduction of Intermediate Coronary Atherosclerosis) study.

Whether combination lipoprotein therapy targeting apolipoprotein B (apoB)- and apoA-containing lipoprotein particles and triglycerides (TGs) in low-risk, asymptomatic subjects with coronary atherosclerosis alters the natural progression of plaques is unknown. This study was designed to compare the progression of coronary atherosclerosis in asymptomatic, low-risk subjects without previously known coronary artery disease but with the presence of plaque on a combination of atorvastatin 40 mg plus fenofibric acid 135 mg daily for 18 months, using cardiovascular computed tomography (CCT). This is an investigator-initiated, single-center, prospective, double-blind, randomized, placebo-controlled, parallel-arm study. Asymptomatic subjects at low risk of cardiovascular events defined as <10% 10-year risk based on the Framingham Risk Score will be recruited, if they do not qualify for lipoprotein-lowering therapy based on the National Cholesterol Education Panel Adult Treatment Panel III guidelines. Subjects will qualify based on lipid parameters if their low-density lipoprotein cholesterol is >/=100 mg/dL and <190 mg/dL, TGs are >150 mg/dL, and the TGs/high-density lipoprotein cholesterol ratio is >3.5. Patients must have nonobstructive plaque based on CCT. Randomization will be 1:1 to either a combination of atorvastatin 40 mg plus fenofibric acid 135 mg daily or placebo for 18 months. Patients will undergo CCT at baseline and at the end of the treatment period. The primary end point will be the between-group difference in percent atheroma volume. Ultimately, this study can guide physicians about the use of a statin-fibric acid derivative combination in asymptomatic, low-risk persons with atherosclerosis.