Attenuated plaque at nonculprit lesions in patients enrolled in intravascular ultrasound atherosclerosis progression trials.

OBJECTIVES: We investigated attenuated plaque (hypoechoic plaque with deep ultrasonic attenuation despite absence of bright calcium) in nonculprit lesions. BACKGROUND: Recent intravascular ultrasound (IVUS) studies describe acoustic shadowing behind large, echolucent, acute culprit lesion sites in the absence of bright calcium. Such "attenuated plaque" is considered a characteristic of high-risk lesions, but its prevalence in stable nonculprit lesions is incompletely known. METHODS: We reviewed IVUS pullback data from nonculprit vessels in 159 patients from the ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden) trial. We identified attenuated plaque and compared volumetric IVUS data in the segments with and without attenuation. In addition, we described plaque morphology in segments with attenuation at baseline and follow-up. RESULTS: Attenuated plaque was found in 17 of 159 patients (10.7%, 95% confidence interval: 6% to 17%). At baseline, there were no significant differences in clinical presentation and cardiovascular risk factors between patients with and without attenuation. Other than a greater plaque eccentricity index (p = 0.008), there were no significant differences between segments with and without attenuation. In segments with attenuated plaque, expansive remodeling was observed in 53%, and calcified plaque adjacent to the attenuation site in 70% of patients. During follow-up, attenuation remained stable, and no events occurred in the patients with attenuation. CONCLUSIONS: Attenuated plaque is present in a significant number of nonculprit segments in patients enrolled in IVUS progression trials and remains stable during follow-up. There is a relationship with mixed calcified lesions. These findings challenge the prior assumption that attenuated plaque is a finding limited to culprit lesions associated with acute clinical presentation.

Beta-blockers and progression of coronary atherosclerosis: pooled analysis of 4 intravascular ultrasonography trials.

BACKGROUND: In patients with myocardial infarction, beta-adrenergic blockers reduce recurrent myocardial infarction and total mortality rates. However, whether a direct influence of beta-blockers on coronary atherosclerosis contributes to reduced recurrent myocardial infarction and total mortality rates is not known. OBJECTIVE: To assess whether beta-blocker therapy is associated with reduced atheroma progression in adults with known coronary artery disease. DESIGN: Post hoc, pooled analysis of individual patient data from 4 intravascular ultrasonography (IVUS) trials. SETTING: Four IVUS trials conducted in the United States, Europe, and Australia. PATIENTS: 1515 patients with coronary artery disease. INTERVENTION: The original trials used 3 different statins, a calcium-channel blocker, an angiotensin-converting enzyme inhibitor, or an acyl coenzyme A-cholesterol acyltransferase inhibitor. MEASUREMENTS: Changes in atheroma volume, as determined by IVUS after adjustment for possible confounders by using linear mixed-effects models, were compared in patients who did and did not receive concomitant beta-blocker treatment. RESULTS: Patients who received beta-blockers (n = 1154) were more likely to have histories of myocardial infarction, angina, and hypertension than were patients who did not receive beta-blockers (n = 361). The estimated annual change in atheroma volume was statistically significantly less in patients who received beta-blockers. This was true for univariate and multivariable analyses that controlled for history of myocardial infarction, angina, and hypertension (mean [+/-SE] atheroma volume, -2.4 +/- 0.5 mm3/y in treated patients vs. -0.4 +/- 0.8 mm3/y in untreated patients; P = 0.034). Accordingly, atheroma volume statistically significantly decreased at follow-up IVUS in patients who received beta-blockers (P < 0.001) and did not change in patients who did not receive beta-blockers (P = 0.86). Additional adjustments for low-density lipoprotein cholesterol level, concomitant medications, and clinical trial did not change the results. LIMITATIONS: Patients were not randomly assigned to beta-blocker therapy, and interventions other than beta-blocker therapy could have influenced the changes in atheroma volume. Whether progression rate of atherosclerosis as detected by IVUS predicts cardiovascular outcomes is unknown. CONCLUSIONS: The analysis demonstrates that beta-blockers can slow progression of coronary atherosclerosis. The findings provide additional support for the current clinical guidelines advocating long-term use of beta-blockers to treat most forms of coronary artery disease.

Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial.

BACKGROUND: Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations. CONCLUSIONS: Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Non-invasive assessment of plaque morphology and remodeling in mildly stenotic coronary segments: comparison of 16-slice computed tomography and intravascular ultrasound.

BACKGROUND: Non-invasive identification and characterization of mildly stenotic atherosclerotic lesions is an increasingly important focus of coronary imaging. DESIGN: We examined the accuracy of multi (16)-slice computed tomography (MSCT) for imaging of these lesions in comparison with intravascular ultrasound (IVUS). MATERIALS: Mildly stenotic segments of the left coronary artery were identified by coronary angiography and analyzed using IVUS and contrast-enhanced MSCT. Independent reviewers evaluated the accuracy of MSCT for presence, composition and distribution of atherosclerotic plaque and remodeling response in comparison to IVUS using receiver operating characteristic (ROC) data analysis. RESULTS: Of 46 segments in 14 patients, diagnostic characterization by MSCT was possible in 37 (80.4%) segments. In these segments the accuracy of MSCT for identifying plaque presence, calcification, distribution and positive remodeling was consistently greater than 0.90 (reader 1) and 0.87 (reader 2). CONCLUSION: State-of-the-art MSCT can accurately identify mildly stenotic coronary atherosclerosis and provide an assessment of morphology and remodeling response.

Characteristics of atherosclerotic plaque distribution in coronary artery bifurcations: an intravascular ultrasound analysis.

OBJECTIVE: Vessel bifurcations are prone to atherosclerotic plaque accumulation. Using volumetric intravascular ultrasound analysis, we investigated atheroma distribution at human coronary bifurcations in vivo. METHODS: We analyzed plaque distribution in 49 left anterior descending coronary artery-diagonal and 20 left circumflex coronary artery-obtuse marginal bifurcations with <50% angiographic stenosis. Cross-sections were analyzed at 1 mm intervals in segments 5 mm proximal and distal from the bifurcation. Planimetry of the lumen and external elastic membrane (EEM) was performed and plaque thickness measured at four different points relative to the branch: 0 degrees, 90 degrees, 180 degrees and 270 degrees. EEM, lumen and plaque volume and percentage plaque burden (plaque volume/EEM volume) were calculated in the proximal and distal segments. The side-branch take-off angle was analyzed in the cross-sectional images. RESULTS: Volumetric analysis showed that EEM, lumen and plaque were larger (P<0.001) in proximal segments than distal segments, whereas percent plaque burden was similar in these segments. Plaque accumulated on the opposite wall to the flow divider. Plaque distribution tended to be more eccentric in distal segments (P=0.05) compared to proximal segments. In 26 of 69 lesions, an asymmetric side-branch take-off was found and was associated with asymmetric plaque distribution compared to those lesions that had a symmetric side-branch take-off (P<0.01). CONCLUSION: We found characteristic patterns of plaque distribution at coronary bifurcations. Proximal segments demonstrated larger plaque volume than distal segments, despite similar percentages of plaque burden. Plaque volume accumulated opposite to the flow divider, especially in distal segments. The side-branch take-off angle in the cross-sectional plane influenced the plaque distribution in bifurcation lesions.

Variability of area measurements obtained with different intravascular ultrasound catheter systems: Impact on clinical trials and a method for accurate calibration.

BACKGROUND: Atherosclerotic plaque burden is the major end point in ongoing progression trials. Intravascular ultrasound allows precise measurements of coronary artery dimensions. However, the variability of measurements among different catheter systems is incompletely characterized. METHODS: Intravascular ultrasound imaging was performed in a cylindric phantom with 5 sections of different, known, cross-sectional area ranging from 3.24 to 27.99 mm(2). A total of 3637 measurements with different catheter systems (Atlantis SR and Ultracross, Scimed/Boston Scientific; and Invision and Avanar, Jomed) were performed. Measurements were divided into model building and validation datasets. For each catheter, calibration models were developed. RESULTS: Overestimation and underestimation of the true cross-sectional area of up to 18% was observed with different catheter systems. Calibration equations for the different systems could be developed that predicted the true diameter and area with high statistical precision (adjusted R(2) > 0.99). CONCLUSIONS: Area measurements vary among different intravascular ultrasound catheter systems. Calibration equations can correct for these differences and allow the comparison of measurements among catheters.