Insights into echo-attenuated plaques, echolucent plaques, and plaques with spotty calcification: novel findings from comparisons among intravascular ultrasound, near-infrared spectroscopy, and pathological histology in 2,294 human coronary artery segments.

OBJECTIVES: Three intravascular ultrasound (IVUS) signatures have been associated with coronary artery disease instability: echo attenuation, an intraplaque echolucent zone, and spotty calcification. The aim of this study was to investigate the substrates responsible for these IVUS signatures in a relatively large series of post-mortem human coronary samples. BACKGROUND: The exact mechanisms and pathological correlates underlying echo attenuation, an intraplaque echolucent zone, and spotty calcification remain poorly understood. METHODS: IVUS was compared with near-infrared spectroscopic detection of lipid core plaque and histopathology in 2,294 vessel segments from 151 coronary specimens from 62 patients at necropsy using the modified American Heart Association classification. RESULTS: IVUS detected echo-attenuated plaques in 18.3% of segments, echolucent plaques in 10.5% of segments, and spotty calcification in 14.4% of segments. Histopathologically, 91.4% of echo-attenuated plaques corresponded to either a fibroatheroma (FA) with a necrotic core (NC) or pathological intimal thickening with a lipid pool; almost all segments with superficial echo attenuation indicated the presence of an FA with an advanced NC. Echolucent plaques indicated the presence of a relatively smaller lipid or NC compared with echo-attenuated plaques (thickness: 0.51 mm [interquartile range (IQR): 0.35 to 0.64 mm] vs. 0.70 mm [IQR: 0.54 to 0.92 mm] [p < 0.001]; arc: 74.5° [IQR: 59.0° to 101.0°] vs. 90° [IQR: 70.0° to 112.0°] [p < 0.001]), although 82.8% of superficial echolucent zones indicated an NC-containing FA. IVUS spotty calcification, especially when superficial in location (72.6%), was often associated with an FA with calcium deposits and had smaller arcs of calcium in the setting of FA compared with fibrocalcific plaques (37.5° [IQR: 23.0° to 53.0°] vs. 59.0° [IQR: 46.0° to 69.0°]; p < 0.001). Comparisons between IVUS and near-infrared spectroscopy revealed that echo-attenuated plaques contained the highest probability of near-infrared spectroscopy-derived lipid core plaque, followed by echolucent plaques and spotty calcifications. CONCLUSIONS: This study demonstrated that echo-attenuated plaque, especially superficial echo attenuation, was the most reliable IVUS signature for identifying a high-risk plaque (i.e., an FA containing a large NC).

Definitions and methodology for the grayscale and radiofrequency intravascular ultrasound and coronary angiographic analyses.

OBJECTIVES: In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radiofrequency intravascular ultrasound (IVUS)-virtual histology (VH), larger plaque burden, smaller luminal area, and plaque composition thin-cap fibroatheroma emerged as independent predictors of future adverse cardiovascular events. BACKGROUND: The methodology for IVUS-VH classification for an in vivo natural history study and the prospective image mapping by angiography and grayscale and IVUS-VH have not been established. METHODS: All culprit and nonculprit lesions (defined as ≥ 30% angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as well as all ≥ 1.5-mm-diameter side branches were divided into 29 CASS (Coronary Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm-long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with lesions defined as having more than 3 consecutive slices with ≥ 40% plaque burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma; 3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific plaque. The locations of angiographic and grayscale and IVUS-VH lesions were recorded in relation to the corresponding coronary artery ostium and nearby side branches. RESULTS: The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions associated with recurrent events were characterized by a plaque burden ≥ 70% (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a minimal luminal area ≤ 4.0 mm(2) (hazard ratio: 3.21; 95% confidence interval: 1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001). CONCLUSIONS: Three-vessel multimodality coronary artery imaging was feasible and allowed the identification of lesion-level predictors for future events in this natural history study.

In vivo characterization of coronary plaques: novel findings from comparing greyscale and virtual histology intravascular ultrasound and near-infrared spectroscopy.

AIMS: To test the hypothesis that near-infrared spectroscopy (NIRS) combined with intravascular ultrasound (IVUS) would provide novel information of human coronary plaque characterization. METHODS AND RESULTS: Greyscale-IVUS, virtual histology (VH)-IVUS, and NIRS were compared in 131 native lesions (66 vessels) that were interrogated during catheterization by all three modalities. Greyscale-IVUS detected attenuated and echolucent plaques correlated with NIRS-detected lipid-rich areas. Attenuated plaques contained the highest NIRS probability of lipid core, followed by echolucent plaques. By VH-IVUS, 93.5% of attenuated plaques contained confluent necrotic core (NC) and were classified as VH-derived fibroatheromas (FAs). Although 75.0% of echolucent plaques were classified as VH-FAs, VH-NC was seen surrounding an echolucent zone, but not within any echolucent zone; and echolucent zones themselves contained fibrofatty and/or fibrous tissue. All calcified plaques with arc >90° contained >10% VH-NC (range 16.0-41.2%) and were classified as calcified VH-FAs, but only 58.5% contained NIRS-detected lipid core. A positive relationship between VH-derived %NC and NIRS-derived lipid core burden index was found in non-calcified plaques, but not in calcified plaques. CONCLUSION: Combining NIRS with IVUS contributes to the understanding of plaque characterization in vivo. Further studies are warranted to determine whether combining NIRS and IVUS will contribute to the assessment of high-risk plaques to predict outcomes in patients with coronary artery disease.

Histopathologic validation of the intravascular ultrasound diagnosis of calcified coronary artery nodules.

A calcified nodule is a type of potentially vulnerable plaque accounting for approximately 2% to 7% of coronary events. Because its intravascular ultrasound (IVUS) features have never been validated, the aim of this study was to assess the IVUS characteristics of calcified nodules in comparison to histopathology. IVUS was performed in 856 pathologic slices in 29 coronary arteries (11 left anterior descending, 5 left circumflex, and 13 right coronary arteries) in 18 autopsy hearts. Pathologic sections were analyzed every 2 mm; qualitative and quantitative findings of matched IVUS were analyzed. IVUS detected calcification in 285 frames; 17 (6.0%) were calcified nodules, and 268 (94.0%) were non-nodular calcium by histopathology. Two calcified nodules (11.8%) were solitary, and 15 (88.2%) were adjacent to non-nodular calcium. IVUS characteristics of calcified nodules were (1) a convex shape of the luminal surface (94.1% in calcified nodules vs 9.7% in non-nodular calcium, p <0.001), (2) a convex shape of the luminal side of calcium (100% vs 16.0%, p <0.001), (3) an irregular luminal surface (64.7% vs 11.6%, p <0.001), and (4) an irregular leading edge of calcium (88.2% vs 19.0%, p <0.001). Luminal area at the calcified nodule site was larger (6.2 ± 2.4 vs 4.3 ± 1.6 mm(2), p <0.001) and plaque burden less (57 ± 6% vs 68 ± 5%, p <0.001) than at the minimum luminal area site. In conclusion, calcified nodules have distinct IVUS features (irregular and convex luminal surface) permitting their prospective identification in vivo.

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.

The effect of pH and viscosity on bovine spermatozoa motility under controlled conditions.

Infertility in a large proportion of infertile couples is due, in part, to the male factor. Spermatozoa must survive the unique environment of the female reproductive tract in their path to fertilize the ovum. This fact is even more problematic for men with oligospermia. Of the many environmental factors that effect sperm motility in the female reproductive tract, we have decided to concentrate on the effect of pH and viscosity on bovine spermatozoa in the laboratory setting. Follicular fluid was harvested from heifer ovaries to serve as a chemo-attractant. Through image analysis, our data shows trends of sperm motility as a function of pH and viscosity. There is a significant increase in the number of immotile sperm seen as pH decreases from 6.5 to 6.0. Furthermore, an exponential relationship between sperm speed and environmental viscosity was observed in vitro. This suggests that modulating vaginal pH and vaginal secretion viscosity could greatly affect spermatozoa motility and therefore male fertility.

Comparison of angiographic and intravascular ultrasonic detection of myocardial bridging of the left anterior descending coronary artery.

The purpose of this study was to determine the incidence, location, and clinical features of myocardial bridging (MB) detected by intravascular ultrasound (IVUS) and to compare IVUS-detectable versus angiographically detectable MBs. IVUS images were analyzed in 331 consecutive patients with de novo coronary lesions located in the left anterior descending coronary artery (LAD). MB was defined as a segment of coronary artery having systolic compression and echocardiographically lucent muscle surrounding the artery (IVUS) or systolic milking (angiography). Although angiography detected MB in only 3% of patients (11 of 331), 75 MB segments (23%, 75 of 331, p <0.001) were identified by IVUS. Maximum plaque burden within the MB segment measured only 25 +/- 7%, and abnormal intimal thickness (defined as >or=0.5 mm) was not observed within the bridged segment of any patient with MB, although the study population had advanced atherosclerosis. Vessel and lumen areas in the MB segment were significantly smaller than those in adjacent proximal and even distal reference segments. Angiographically detectable MB was significantly longer, located more proximally in the LAD, and had more severe systolic compression by IVUS. Angiographically silent MB more often occurred in the presence of an adjacent proximal stenosis and lower left ventricular ejection fraction. In conclusion, IVUS may provide useful anatomic information for the accurate diagnosis of MBs that are largely angiographically silent. IVUS-detectable MBs were observed in approximately 1/4 of patients undergoing LAD imaging at our center.

In vivo virtual histology intravascular ultrasound correlates of risk factors for sudden coronary death in men: results from the prospective, multi-centre virtual histology intravascular ultrasound registry.

AIMS: We hypothesized a relationship between virtual histology intravascular ultrasound (VH-IVUS) findings and risk factors histopathologically associated with sudden coronary death (SCD) in men: cigarette smoking and an increased total cholesterol-to-high-density lipoprotein cholesterol (HDL-C) ratio (TC/HDL > 5). METHODS AND RESULTS: We assessed volumetric VH-IVUS parameters in a consecutive series of 473 male patients: fibrous, fibro-fatty, dense calcium (DC), necrotic core (NC), and a calculated NC/DC ratio. Patients' age was 61 ± 11 years, with 27% smokers and 69% having a lipid disorder. The NC/DC ratio was the only VH-IVUS parameter related to both TC/HDL ratio (r = 0.18, P= 0.0008) and low-density lipoprotein cholesterol levels (r = 0.17, P= 0.002); had a negative correlation with HDL-C levels (r = -0.11, P= 0.03); and was higher for smokers [median 1.98 (1.35-3.18)] vs. non-smokers [median 1.70 (1.23-2.53), P= 0.006]. An NC/DC value >3 was the threshold that best identified smokers and/or patients presenting TC/HDL >5 (odds ratio 3.0, 95% CI 1.7-4.9, P= 0.0001), and receiver-operator curves showed the superiority of the NC/DC ratio [area under curve (AUC) 0.64, P < 0.0001] over %DC (AUC 0.58, P= 0.006) or %NC (AUC 0.51, P= 0.43) to identify these patients. CONCLUSION: The ratio of NC to calcification detected by VH-IVUS in diseased coronary segments is related to known risk factors for SCD and, thus, may be associated with a worse prognosis.

Nonrandomized comparison of coronary stenting under intravascular ultrasound guidance of direct stenting without predilation versus conventional predilation with a semi-compliant balloon versus predilation with a new scoring balloon.

This study was conducted to determine the influence of lesion preparation using the AngioSculpt balloon on final stent expansion. Stent expansion remains an important predictor of restenosis and subacute thrombosis, even in the drug-eluting stent (DES) era. In these patients, the role of different predilation strategies has yet to be established. Two hundred ninety-nine consecutive de novo lesions treated with 1 >2.5-mm DES (Cypher or Taxus) under intravascular ultrasound guidance without postdilation, using 3 implantation strategies, were studied: (1) direct stenting without predilation (n = 145), (2) predilation with a conventional semi-compliant balloon (n = 117), and (3) predilation with the AngioSculpt balloon (n = 37). Stent expansion was defined as the ratio of intravascular ultrasound-measured minimum stent diameter and minimum stent area to the manufacturer's predicted stent diameter and area. These ratios were larger after AngioSculpt predilation, and a greater percentage of stents had final minimum stent areas >5.0 mm(2) (another commonly accepted criterion of adequate DES expansion). Lesion morphology, stent and lesion length, and reference vessel size did not affect DES expansion. In conclusion, in this observational, nonrandomized study, pretreatment with the AngioSculpt balloon enhanced stent expansion and minimized the difference between predicted and achieved stent dimensions.

Intravascular ultrasound assessment of drug-eluting stent expansion.

BACKGROUND: In the drug-eluting stent (DES) era, stent expansion remains an important predictor of restenosis and subacute thrombosis. Compliance charts are developed to predict final minimum stent diameter (MSD) and area (MSA). The objectives of the study were (1) to assess DES expansion by comparing intravascular ultrasound (IVUS)-measured MSD and MSA against the values predicted by compliance charts and (2) to compare each DES against its bare-metal stent (BMS) equivalent. METHODS: We enrolled 200 patients with de novo coronary lesions treated with single, >2.5-mm Cypher (Cordis, Johnson & Johnson, Miami Lakes, FL) (sirolimus-eluting stent [SES], 133 patients) or Taxus (Boston Scientific, Natick, MA) (paclitaxel-eluting stent [PES], 67 patients) stent under IVUS guidance without another postdilation balloon. We used a comparison cohort of 65 equivalent BMS (Express 2 [Boston Scientific], 37 patients; Bx Velocity [Cordis, Johnson & Johnson], 28 patients) deployed under similar conditions. RESULTS: The DES achieved only 75% +/- 10% of predicted MSD and 66% +/- 17% of predicted MSA; this was similar for SES and PES. Furthermore, 24% of SES and 28% of PES did not achieve a final MSA of 5 mm(2), a consistent predictor of DES failure. The SES achieved 75% +/- 10% of predicted MSA versus 75% +/- 9% for Bx Velocity (P = .9). The PES achieved 79.9% +/- 14% of predicted MSA versus 79% +/- 10% for Express 2 (P = .8). Lesion morphology, arc and length of calcium, stent diameter and length, and implantation pressures did not affect expansion. CONCLUSIONS: Compliance charts fail to predict final MSD and MSA. A considerable percentage of DES does not achieve minimum standards of stent expansion. The SES and PES achieve similar expansion to their BMS platform, indicating that the polymer coating does not affect DES expansion in vivo. However, stent expansion cannot be predicted from preintervention IVUS lesion assessment.