The aim of this pilot study was to test the prognostic value of serial measurements of peripheral endothelial function, assessed by brachial artery flow-mediated dilation (FMD), in patients with angiographically proven coronary artery disease. In 68 patients, FMD was measured on the day after coronary angiography and again after a mean of 14 +/- 12 months. Patients were divided into two groups: absolute improvement in FMD > or = 3%(FMD-improver = FMD-i) and < 3%(FMD-non-improver = FMD-ni). After a mean follow-up of 44 +/- 12 months, cardiovascular events were recorded. Baseline characteristics were similar between groups, except the number of risk factors which was smaller in FMD-i (1.6 +/- 0.7 vs 2.1 +/- 0.9, p < 0.02). Cardiovascular events were more frequent in FMD-ni (9 vs 1 event; p < 0.05). In Kaplan-Meier analysis, a trend towards a better outcome in patients with improved FMD was found using the log-rank test (p = 0.08). The single baseline FMD showed no relationship with late cardiovascular events. Thus,'delta-FMD' may be more closely related to prognosis than a single FMD measurement.

BACKGROUND: Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully explored. OBJECTIVE: To determine whether carotid arterial intima-media thickness predicts coronary events. DESIGN: Long-term follow-up (average, 8.8 years) of a previously assembled cohort of persons who completed the 2-year Cholesterol Lowering Atherosclerosis Study, a randomized arterial imaging trial designed to study the effects of lipid lowering on progression of atherosclerosis. SETTING: University-based ultrasonography laboratory. PATIENTS: 146 men 40 to 59 years of age who had previously had coronary artery bypass graft surgery. MEASUREMENTS: Preintrusive atherosclerosis in the common carotid artery was evaluated every 6 months with B-mode ultrasonography, and intrusive atherosclerosis in the coronary arteries was evaluated at baseline and at 2 years with quantitative coronary angiography. After the trial, the incidences of coronary events (nonfatal acute myocardial infarction, coronary death, and coronary artery revascularization) were documented. RESULTS: For each 0.03-mm increase per year in carotid arterial intima-media thickness, the relative risk for nonfatal myocardial infarction or coronary death was 2.2 (95% CI, 1.4 to 3.6) and the relative risk for any coronary event was 3.1 (CI, 2.1 to 4.5)(P < 0.001). Absolute intima-media thickness was also related to risk for clinical coronary events (P < 0.02). Absolute thickness and progression in thickness predicted risk for coronary events beyond that predicted by coronary arterial measures of atherosclerosis and lipid measurements (P < 0.001). CONCLUSION: Noninvasive B-mode ultrasonographic measurement of progression of intima-media thickness in the distal common carotid artery is a useful surrogate end point for clinical coronary events.

BACKGROUND: To test the hypothesis of general atherosclerotic plaque destabilization during acute coronary syndrome (ACS), the present study sought to analyze the 3 coronary arteries by systematic intravascular ultrasound scan (IVUS). METHODS AND RESULTS: Seventy-two arteries were explored in 24 patients referred for percutaneous coronary intervention after a first ACS with troponin I elevation. Fifty plaque ruptures (mean, 2.08 per patient; range, 0 to 6) were diagnosed by the association of a ruptured capsule with intraplaque cavity. Plaque rupture on the culprit lesion was found in 9 patients (37.5%). At least 1 plaque rupture was found somewhere other than on the culprit lesion in 19 patients (79%). These lesions were in a different artery than the culprit artery in 70.8% and were in both other arteries in 12.5% of these 24 patients. Complete IVUS examination of all 3 coronary axes in patients who had experienced a first ACS revealed that multiple atherosclerotic plaque ruptures were detected by IVUS; these multiple ruptures were present simultaneously with the culprit lesion; they were frequent and located (in three quarters of cases) on the 3 principal coronary trunks; and the multiple plaque ruptures in locations other than on the culprit lesion were less severe, nonstenosing, and less calcified. CONCLUSION: Although one single lesion is clinically active at the time of ACS, the syndrome seems nevertheless associated with overall coronary instability.

BACKGROUND. Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. METHODS AND RESULTS. A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media. CONCLUSIONS. Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.

CONTEXT: The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. OBJECTIVE: To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). INTERVENTIONS: Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. MAIN OUTCOME MEASURES: The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. RESULTS: Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P =.003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P =.16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P =.10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P =.12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P =.02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P =.08), and no progression in the amlodipine group (P =.31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P =.07. CONCLUSIONS: Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.

OBJECTIVES. This study was designed to establish the relation between ultrasound-derived atheroma morphology and the clinical, procedural and angiographic features of patients presenting for coronary angioplasty. BACKGROUND. Intracoronary ultrasound imaging provides accurate dimensional information regarding arterial lumen and wall structures. Atheroma composition may also be assessed by ultrasound; however, only limited studies have been performed in patients. METHODS. In 65 patients a diagnostic ultrasound imaging catheter or a combination imaging-angioplasty balloon catheter was used during coronary angioplasty to image both the lesion and the vessel segment just proximal to it (reference segment). Ultrasound images were analyzed for lumen, total vessel and plaque areas and were classified into five morphologic subtypes (soft, fibrous, calcific, mixed plaque and concentric subintimal thickening). These data were compared with angiographic morphologic features, procedural results and clinical angina pattern (stable vs. unstable). RESULTS. Morphologic analysis of the ultrasound images obtained from the lesion correlated well with the clinical angina syndrome. Compared with patients with stable angina, patients with unstable angina had more soft lesions (74% vs. 41%), fewer calcified and mixed plaques (fibrotic, soft or calcific components in one or more combinations [25% vs. 59%]) and fewer intralesional calcium deposits (16% vs. 45%)(all p < 0.01). There was no correlation between ultrasound and angiographic lesion morphologic characteristics for either the reference segment or the lesion. Ultrasound demonstrated greater sensitivity than angiography for identifying unstable lesions (74% vs. 40%). Dimensional analysis demonstrated a large plaque burden in the reference segments (45 +/- 15% of total vessel area). Postangioplasty plaque burden was also high (62 +/- 9%). There was a significant, but only fair correlation between lumen area determined by angiography and ultrasound for both the reference segment (r = 0.70, p < 0.001) and the postangioplasty lesion (r = 0.63, p < 0.05). CONCLUSIONS. Morphologic plaque classification by ultrasound is closely correlated to clinical angina but has little relation to established angiographic morphologic characteristics. Intracoronary ultrasound imaging during angioplasty identifies a large residual plaque burden in both the reference segment and the lesion. In the future, determination of plaque composition by intracoronary ultrasound may be important in selecting or modifying interventional therapeutic options.

BACKGROUND: The safety and efficacy of sirolimus-eluting stenting have been demonstrated, but the outcome of patients treated with this novel technology beyond the first year remains unknown. We sought to evaluate the angiographic, intravascular ultrasound (IVUS), and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation. METHODS AND RESULTS: This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR], n=15, and fast release [FR], n=15) in São Paulo, Brazil. Twenty-eight patients underwent 2-year angiographic and IVUS follow-up. No deaths occurred during the study period. In-stent late loss was slightly greater in the FR group (0.28+/-0.4 mm) than in the SR group (-0.09+/-0.23 mm, P=0.007). No patient had in-stent restenosis. At 2-year follow-up, only 1 patient (FR group) had a 52% diameter stenosis within the lesion segment, which required repeat revascularization. The target-vessel revascularization rate for the entire cohort was 10%(3/30) at 2 years. All other patients had < or =35% diameter stenosis. Angiographic lumen loss at the stent edges was also minimal (in-lesion late loss was 0.33+/-0.42 mm [FR] and 0.13+/-0.29 mm [SR]). In-stent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 2 years (FR= 9.90+/-9 mm3 and SR=10.35+/-9.3 mm3). CONCLUSIONS: This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans. In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups, although angiographic lumen loss was slightly higher in the FR group. Restenosis "catch-up" was not found in our patient population.

BACKGROUND: Atherosclerotic plaque stability is related to histological composition. However, current diagnostic tools do not allow adequate in vivo identification and characterization of plaques. Spectral analysis of backscattered intravascular ultrasound (IVUS) data has potential for real-time in vivo plaque classification. METHODS AND RESULTS: Eighty-eight plaques from 51 left anterior descending coronary arteries were imaged ex vivo at physiological pressure with the use of 30-MHz IVUS transducers. After IVUS imaging, the arteries were pressure-fixed and corresponding histology was collected in matched images. Regions of interest, selected from histology, were 101 fibrous, 56 fibrolipidic, 50 calcified, and 70 calcified-necrotic regions. Classification schemes for model building were computed for autoregressive and classic Fourier spectra by using 75% of the data. The remaining data were used for validation. Autoregressive classification schemes performed better than those from classic Fourier spectra with accuracies of 90.4% for fibrous, 92.8% for fibrolipidic, 90.9% for calcified, and 89.5% for calcified-necrotic regions in the training data set and 79.7%, 81.2%, 92.8%, and 85.5% in the test data, respectively. Tissue maps were reconstructed with the use of accurate predictions of plaque composition from the autoregressive classification scheme. CONCLUSIONS: Coronary plaque composition can be predicted through the use of IVUS radiofrequency data analysis. Autoregressive classification schemes performed better than classic Fourier methods. These techniques allow real-time analysis of IVUS data, enabling in vivo plaque characterization.

BACKGROUND: Ambulatory blood pressure may be higher or lower than clinic blood pressure. Attention has focused on "white coat hypertension"(normal ambulatory blood pressure elevated in the clinic). The converse phenomenon of high ambulatory blood pressure but normal office blood pressure-"white coat normotension"-has not been studied. OBJECTIVE: To assess whether white coat normotension (awake ambulatory blood pressure > 134/90 mm Hg and clinic blood pressure < 140/90 mm Hg) is associated with target organ damage. DESIGN: Cross-sectional observational study. SETTING: University hospital hypertension center and participant work sites. PATIENTS: 295 clinically normotensive adults and 64 patients with sustained hypertension (elevated clinic and ambulatory blood pressure). MEASUREMENTS: Target organ abnormalities were measured by echocardiography and arterial ultrasonography in 61 patients with white coat normotension, 234 with sustained normotension (normal clinic and ambulatory blood pressure), and 64 with sustained hypertension. RESULTS: Patients with white coat normotension were older; had higher body mass indices, serum creatinine concentrations, and glucose levels; and a higher prevalence of current smokers. Left ventricular mass index and relative wall thickness were higher by 13 g/m2 (CI, 8 to 18 g/m2) and by 0.03 (CI, 0.01 to 0.04), respectively, in patients with white coat normotension compared with those who had sustained normotension. Patients with white coat normotension and those with sustained hypertension did not differ significantly for left ventricular mass index (4 g/m2 [CI,- 3 to 10 g/m2) or relative wall thickness (0.01 [CI,-0.01 to 0.03]). The prevalence of discrete atherosclerotic plaques was similar in patients with white coat normotension (17 of 61, or 28%[CI, 17% to 39%]) and those with sustained hypertension (17 of 64, or 27%[CI, 16% to 38%]), but the difference lost significance after adjustment for age. CONCLUSIONS: White coat normotension is associated with left ventricular mass and carotid wall thickness similar to those in sustained hypertension. The association of white coat normotension with prognostically important target organ damage may partly explain the ability of high normal left ventricular mass and high normal clinic blood pressure to predict subsequent hypertension and cardiovascular events in patients with clinical normotension.

BACKGROUND: Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting. METHODS AND RESULTS: DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%. CONCLUSIONS: During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.

BACKGROUND. To establish a histopathologic basis for angioscopic and ultrasound image interpretation we studied 70 postmortem human arterial segments in vitro. METHODS AND RESULTS. We used 7- to 9-French fiber-optic angioscopes and 20- to 30-MHz intravascular ultrasound imaging catheters. Three observers assigned an angioscopic and ultrasound image classification to each vessel segment. The image and histological classification categories were then compared. The sensitivity, specificity, and accuracy of both methods separately or in combination for normal vessels were each greater than or equal to 95%. The predictive value was better for angioscopy than for ultrasound due to incorrect ultrasound interpretations of normal anatomy in the presence of thrombus. For stable atheroma the sensitivity, specificity, and accuracy of the individual methods were each greater than 90%. However, both angioscopy and ultrasound had classification errors in that disrupted atheroma was identified and classified as stable atheroma. Consequently, the predictive value was 74% for angioscopy and 78% for ultrasound. For disrupted atheroma the sensitivities for angioscopy and ultrasound were only moderate (73% and 81%, respectively), whereas the specificity, accuracy, and predictive value were each high (greater than 90%). For thrombus detection, the specificity, accuracy, and predictive value were high (greater than 93%) for each method. The sensitivity of angioscopy was 100%. However, sensitivity was lower for ultrasound (57%) due to false-negative interpretation of laminar clots in normal vessels and an inability to distinguish disrupted or stable atheroma from intraluminal thrombus. CONCLUSIONS. Contingency analyses showed that each imaging method alone or combined had significant agreement with the results obtained from histology (p less than 0.001). When assessing all cases in which angioscopy and ultrasound were concordant, there was a 92% agreement with the histological classification.