Impact of metabolic syndrome on tissue characteristics of angiographically mild to moderate coronary lesions integrated backscatter intravascular ultrasound study.

OBJECTIVES: We assessed the impact of metabolic syndrome (MetS) on the tissue characteristics of coronary plaques using integrated backscatter intravascular ultrasound (IB-IVUS). BACKGROUND: Metabolic syndrome is associated with the increasing risk of cardiovascular disease. METHODS: We identified MetS by the definition of the National Cholesterol Education Program in Adult Treatment Panel III criterion. Non-target coronary lesions with mild to moderate stenosis were measured by conventional and IB-IVUS parameters using 40-MHz (motorized pullback 0.5 mm/s) intravascular catheter. A total of 20 IB-IVUS images were recorded at an interval of 0.5 mm for 10 mm length in each plaque. The 3-dimensional analyses were performed using commercially available software. RESULTS: The prevalence of MetS was 61 patients (50%) with 73 lesions (49%) among 122 patients with 148 lesions. Patients with MetS showed a significant increase in percentage lipid area (38 +/- 19% vs. 30 +/- 19%, p = 0.02) and percentage lipid volume (39 +/- 17% vs. 33 +/- 17%, p = 0.03), and they also showed a significant decrease in percentage of fibrous volume (57 +/- 14% vs. 61 +/- 13%, p = 0.03). Multivariate regression analysis after adjustment for potentially confounding risk factors showed that MetS remains correlated independently with the percentage of lipid volume (r = 0.223, p = 0.01). Logistic regression analysis after adjusting for confounding and non-MetS coronary risk factors showed that MetS (odds ratio 4.00, 95% confidence interval 1.33 to 12.0, p = 0.01) is proved to be an independent predictor of the lipid-rich plaque. CONCLUSIONS: Metabolic syndrome is associated with lipid-rich plaques, contributing to the increasing risk of plaque vulnerability.     

Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images

OBJECTIVES: The purpose of the present study was to define clinicopathologically whether integrated backscatter (IB) combined with conventional two-dimensional echo (2DE) can differentiate the tissue characteristics of calcification (CL), fibrosis (FI), lipid pool (LP) with fibrous cap, intimal hyperplasia (IH) and thrombus (TH) and can construct two-dimensional tissue plaque structure in vivo. BACKGROUND: It is difficult to characterize the components of plaque using conventional 2DE techniques. METHODS: Integrated backscatter values of plaques were measured in the right common carotid and femoral arteries (total 24 segments) both during life and after autopsy in 12 patients (age 68 to 84 years, 10 men and two women). Integrated backscatter values were determined using a 5-12 MHz multifrequency transducer, setting the region of interests (ROIs) (11 x 11 pixels) on the echo tomography of the entire arterial wall (55 +/- 10 ROI/segment) and comparing it with histologic features in the autopsied arterial specimens. RESULTS: Corrected IB values obtained before death and at autopsy were significantly correlated (r = 0.93, p < 0.01). Corresponding to the histologic features, corrected IB values on the rectangle ROIs obtained during life were divided into five categories: category 1 (TH) 4 < IB < or = 6; category 2 (media and IH or LP in the intima) 7 < IB < or = 13; category 3 (FI) 13 < IB < or = 18, category 4 (mixed lesion) 18 < IB < or = 27 and category 5 (CL) 28 < IB < or = 33. In category 2, media and intima were differentiated using conventional 2DE. Under the above procedures, color-coded maps constructed with IB-2DE obtained during life precisely reflected the histologic features of media and intima. CONCLUSIONS: Integrated backscatter with 2DE represents a useful noninvasive tool for evaluating the tissue structure of human plaque.     

Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound

OBJECTIVES: The purpose of the present study was twofold: 1) to evaluate the usefulness of three-dimensional (3D) integrated backscatter (IB) intravascular ultrasound (IVUS) for quantitative tissue characterization of coronary plaques; and 2) to use this imaging technique to determine if six months of statin therapy alters the tissue characteristics of coronary plaques. BACKGROUND: Three-dimensional IVUS techniques for quantitative tissue characterization of plaque composition have not been developed. METHODS: Radiofrequency (RF) signals were obtained using an IVUS system with a 40-MHz catheter. The IB values of the RF signal were calculated and color-coded. The 3D reconstruction of the color-coded map was performed by computer software. A total of 18 IB IVUS images were captured at an interval of 1 mm in each plaque. A total of 52 patients with hyperlipidemia were randomized to treatment with pravastatin (20 mg/day, n = 17), atorvastatin (20 mg/day, n = 18), or diet (n = 17) for six months. The tissue characteristics of arterial plaque in each patient (one arterial segment per patient) were analyzed with 3D IB IVUS before and after treatment. RESULTS: Significant increases of fibrous volume (pravastatin: 25.4 +/- 6.5% to 28.1 +/- 6.1%; atorvastatin: 26.2 +/- 5.7% to 30.1 +/- 5.5%) and mixed lesion volume (atorvastatin: 25.5 +/- 6.6% to 28.7 +/- 5.1%) and a reduction of lipid volume (pravastatin: 25.5 +/- 5.7% to 21.9 +/- 5.3%; atorvastatin: 26.5 +/- 5.2% to 19.9 +/- 5.5%) were observed after statin therapy. CONCLUSIONS: Statin therapy reduced the lipid component in patients with stable angina without reducing the degree of stenosis. Three-dimensional IB IVUS offers the potential for quantitative volumetric tissue characterization of coronary atherosclerosis.     

Assessment of vulnerable plaques causing acute coronary syndrome using integrated backscatter intravascular ultrasound.

OBJECTIVES: This study aims to define tissue characteristics of vulnerable plaques before acute coronary syndrome (ACS) by use of integrated backscatter intravascular ultrasound (IB-IVUS). BACKGROUND: Tissue characterization of coronary plaques is possible with the use of IB-IVUS. METHODS: The subjects were 140 patients with angina pectoris, and we selected 160 coronary lesions without significant stenosis for evaluation. Ultrasound signals were obtained by an IVUS system using a 40-MHz catheter. RESULTS: At the follow-up (30 +/- 7 months), 12 plaques caused ACS after the initial IVUS examination. Ten of the 12 plaques had IVUS parameters recorded at baseline. These 10 plaques were classified as vulnerable plaques (VP), and the other plaques were classified as stable plaques (SP; n = 143). There was no significant difference of vessel area, lumen area, and plaque area between VP and SP. However, plaque burden (60 +/- 9% vs. 52 +/- 9%; p = 0.014), eccentricity (0.70 +/- 0.10 vs. 0.55 +/- 0.17; p = 0.013), remodeling index (1.30 +/- 0.08 vs. 1.16 +/- 0.16; p = 0.006) and percentage lipid area (72 +/- 10% vs. 50 +/- 16%; p < 0.0001) were greater in VP than in SP. Percentage fibrous area (23 +/- 6% vs. 47 +/- 14%; p < 0.0001) was smaller in VP than in SP. The sensitivities, specificities, and positive predictive values of percentage fibrous area (90%, 96%, and 69%, respectively) and percentage lipid area (80%, 90%, and 42%, respectively) for classifying VP were evaluated. CONCLUSIONS: Tissue characteristics of VP before ACS were different from those of SP. This suggests that VP and SP as classified by IB-IVUS are useful in predicting ACS.     

Intravascular ultrasound imaging of angiographically normal coronary arteries: a prospective study in vivo.

Intravascular ultrasound imaging (IVUS) was performed to elucidate the discrepancy between clinical history and angiographic findings and to measure the diameter and area of the lumen of the normal left coronary artery in 55 patients who presented with chest pain but had normal coronary angiograms. The left coronary artery (LCA) was scanned with a 4.8F, 20 MHz mechanically rotated ultrasound catheter at 413 sites. Atherosclerotic lesions were identified at 72 (17%) sites in 25 patients. The mean (SD) (range) plaque area was 5.55 (3.56) mm2 (2-26 mm2) and it occupied 28.8 (9.6)% (13-70%) of the coronary cross sectional area. Calcification was detected at 24 (33%) atherosclerotic sites in nine patients. The correlation coefficients for the lumen dimensions measured at normal sites by IVUS and by angiography were r = 0.93 (SEE = 0.43) mm for lumen diameter and r = 0.89 (SEE = 4.27) mm2 for lumen area (both p < 0.001). 16 of the 30 patients in whom no atherosclerotic plaques were detected in the LCA lumen by IVUS had no risk factors of coronary artery disease. The cross sectional area of 90 consecutive images of left main coronary artery (LMCA), proximal left anterior descending coronary artery (proximal LAD), and mid LAD was measured in these 16 subjects. The mean (SEM) areas at end diastole were LMCA 17.33 (7.98) mm2; proximal LAD 13.56 (5.85) mm2; mid LAD 9.75 (4.67) mm2. During the cardiac cycle the cross sectional area changed by 10.2 (4.0)% in the LMCA, by 8.3 (4.7)% in the proximal LAD, and by 9.8 (4.0)% in the mid LAD. In 11 patients with plagues the change in cross sectional area in plague segments (5.8(3.1)%) was significantly lower than in the segments from patients without plagues (p < 0.001). Lumen area reached a maximum in early diastole rather than in late diastole. IVUS can imagine atherosclerotic lesions that are angiographically silent; it also provides detailed information about plague characteristics. The variation in coronary cross sectional area during the cardiac cycle should not be ignored during quantitative analysis. Maximum dimensions in normal segments are reached in early diastole. Further studies are needed to clarify the clinical significance of atherosclerosis detected by IVUS in patients presenting with chest pain but normal coronary angiography.     

Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques.

OBJECTIVES: The purpose of the present study was to validate the diagnostic accuracy of optical coherence tomography (OCT), integrated backscatter intravascular ultrasound (IB-IVUS), and conventional intravascular ultrasound (C-IVUS) for tissue characterization of coronary plaques and to evaluate the advantages and limitations of each of these modalities. BACKGROUND: The diagnostic accuracy of OCT for characterizing tissue types is well established. However, comparisons among OCT, C-IVUS, and IB-IVUS have not been done. METHODS: We examined 128 coronary arterial sites (42 coronary arteries) from 17 cadavers; IVUS and OCT images were acquired on the same slice as histology. Ultrasound signals were obtained using an IVUS system with a 40-MHz catheter and digitized at 1 GHz with 8-bit resolution. The IB values of the ultrasound signals were calculated with a fast Fourier transform. RESULTS: Using histological images as a gold standard, the sensitivity of OCT for characterizing calcification, fibrosis, and lipid pool was 100%, 98%, and 95%, respectively. The specificity of OCT was 100%, 94%, and 98%, respectively (Cohen's kappa = 0.92). The sensitivity of IB-IVUS was 100%, 94%, and 84%, respectively. The specificity of IB-IVUS was 99%, 84%, and 97%, respectively (Cohen's kappa = 0.80). The sensitivity of C-IVUS was 100%, 93%, and 67%, respectively. The specificity of C-IVUS was 99%, 61%, and 95%, respectively (Cohen's kappa = 0.59). CONCLUSIONS: Within the penetration depth of OCT, OCT has a best potential for tissue characterization of coronary plaques. Integrated backscatter IVUS has a better potential for characterizing fibrous lesions and lipid pools than C-IVUS.     

Intravascular ultrasound imaging of angiographically normal coronary arteries: an in vivo comparison with quantitative angiography

Intravascular ultrasound, a new technique for real-time two-dimensional visualization of arteries and veins, delineates vessel wall morphology and measures luminal dimensions. This imaging method has been validated with in vitro systems and in peripheral vessels, but there are few in vivo coronary artery studies. Twenty cardiac transplant recipients with no angiographic coronary artery disease were scanned with a 30-MHz intravascular ultrasound catheter from the left main coronary ostium to the mid-left anterior descending coronary artery. Simultaneous angiographic measurements were performed at 76 sites. Ultrasound end-diastolic diameters in two perpendicular axes were 3.8 +/- 0.9 and 3.9 +/- 0.6 mm, respectively, and mean diameter derived from an area determined by planimetry was 3.9 +/- 0.9 mm. Angiographic coronary artery diameters measured with a computer-assisted edge detection system perpendicular to the long axis of the vessel and to the long axis of the catheter were 3.4 +/- 0.8 and 3.6 +/- 0.8 mm, respectively. Luminal diameters measured with the two imaging systems correlated closely, with an r value of 0.86 when ultrasound was compared with the angiographic diameter measured perpendicular to the vessel and 0.88 when compared with the angiographic diameter measured perpendicular to the imaging catheter. Eighty-three percent of the ultrasound-measured diameters were above the line of identity when compared with the simultaneous angiographic measurement. The more the imaging catheter deviated from the long axis of the vessel, the greater was the discrepancy between the ultrasound and angiographic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.     

Impact of tissue characteristics on luminal narrowing of mild angiographic coronary stenosis: assessment of integrated backscatter intravascular ultrasound

Integrated backscatter intravascular ultrasound (IB-IVUS) is a useful method for analyzing coronary plaque tissue. We evaluated whether tissue composition determined using IB-IVUS is associated with the progression of stenosis in coronary angiography. Sixty-three nontarget coronary lesions in 63 patients with stable angina were evaluated using conventional IVUS and IB-IVUS. IB-IVUS images were analyzed at 1-mm intervals for a length of 10 mm. After calculating the relative areas of the tissue components using the IB-IVUS system, fibrous volume (FV) and lipid volume (LV) were calculated through integration of the slices, after which percentages of per-plaque volume (%FV/PV, %LV/PV) and per-vessel volume (%FV/VV, %LV/VV) were calculated. Progression of coronary stenosis was interpreted from the increase in percent diameter stenosis (%DS) from baseline to the follow-up period (6–9 months) using quantitative coronary angiography. %DS was 24.1 ± 12.8 % at baseline and 23.2 ± 13.7 % at follow-up. Using IB-IVUS, LV was 31.7 ± 10.5 mm³, and %LV/PV and %LV/VV were 45.6 ± 10.3 % and 20.2 ± 6.0 %, respectively. FV, %FV/PV, and %FV/VV were 35.5 ± 12.1 mm³, 52.1 ± 9.5 %, and 23.4 ± 7.1 %, respectively. The change in %DS was ?0.88 ± 7.25 % and correlated closely with %LV/VV (r = 0.27, P = 0.03) on simple regression. Multivariate regression after adjustment for potentially confounding risk factors showed %LV/VV to be correlated independently with changes in %DS (r = 0.42, P = 0.02). Logistic regression analysis after adjusting for confounding coronary risk factors showed LV (odds ratio 1.08; 95 % confidence interval 1.01–1.16; P = 0.03) and %LV/VV (odds ratio 1.13; 95 % confidence interval 1.01–1.28; P = 0.03) to be independent predictors of the progression of angiographic coronary stenosis. Our findings suggest that angiographic luminal narrowing of the coronary artery is likely associated with tissue characteristics. IB-IVUS may provide information about the natural progression of luminal narrowing in coronary stenosis.     

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks’ treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.     

Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound

OBJECTIVES: The aim of the present study was to determine the diagnostic accuracy of 64-slice computed tomography (CT) to identify and quantify atherosclerotic coronary lesions in comparison with catheter-based angiography and intravascular ultrasound (IVUS). BACKGROUND: Currently, the ability of multislice CT to quantify the degree of coronary artery stenosis and dimensions of coronary plaques has not been evaluated. METHODS: We included 59 patients scheduled for coronary angiography due to stable angina pectoris. A contrast-enhanced 64-slice CT (Senation 64, Siemens Medical Solutions, Forchheim, Germany) was performed before the invasive angiogram. In a subset of 18 patients, IVUS of 32 vessels was part of the catheterization procedure. RESULTS: In 55 of 59 patients, 64-slice CT enabled the visualization of the entire coronary tree with diagnostic image quality (American Heart Association 15-segment model). The overall correlation between the degree of stenosis detected by quantitative coronary angiography compared with 64-slice CT was r = 0.54. Sensitivity for the detection of stenosis <50%, stenosis >50%, and stenosis >75% was 79%, 73%, and 80%, respectively, and specificity was 97%. In comparison with IVUS, 46 of 55 (84%) lesions were identified correctly. The mean plaque areas and the percentage of vessel obstruction measured by IVUS and 64-slice CT were 8.1 mm2 versus 7.3 mm2 (p < 0.03, r = 0.73) and 50.4% versus 41.1% (p < 0.001, r = 0.61), respectively. CONCLUSIONS: Contrast-enhanced 64-slice CT is a clinically robust modality that allows the identification of proximal coronary lesions with excellent accuracy. Measurements of plaque and lumen areas derived by CT correlated well with IVUS. A major limitation is the insufficient ability of CT to exactly quantify the degree of stenosis.