Coronary intravascular ultrasound: implications for understanding the development and potential regression of atherosclerosis.

The incremental value of intravascular ultrasound (IVUS), compared with angiographic analysis of coronary atherosclerosis, originates principally from 2 key features-its tomographic perspective and the ability to image coronary atheroma directly. Whereas angiography depicts the cross-sectional coronary anatomy as a planar silhouette of the lumen, ultrasound directly images the atheroma within the vessel wall, allowing measurement of atheroma size, distribution, and to some extent, composition. Although angiography remains the principal method to assess the extent of coronary atherosclerosis and to guide percutaneous coronary interventions, IVUS is rapidly altering conventional paradigms in the diagnosis and therapy of coronary artery disease. Thus, IVUS has become a vital adjunctive imaging modality for the aggressive coronary interventional cardiologist. As such, ultrasound has earned a role as a viable complementary technique relative to angiography, rather than an alternative to conventional angiographic methods. This article reviews the rationale, technical advantages and limitations, and interpretation of intravascular ultrasonography from the perspective of the general and invasive cardiologist. We emphasize the impact that IVUS studies have had on our understanding of the atherosclerotic coronary artery disease process, because these findings have important implications for all cardiologists. We then review several trials that are currently using intravascular ultrasonography for the study of coronary artery disease regression.

Prognostic value of absolute versus relative measures of the procedural result after successful coronary stenting: importance of vessel size in predicting long-term freedom from target vessel revascularization.

BACKGROUND: The procedural result is a major determinant of the incidence of 6-month target vessel revascularization (TVR) after successful coronary stenting. However, the prognostic implications of the different measures of the procedural result or procedural end points have not been directly compared. In this study, we sought to assess and compare the impact of achieving different procedural end points on the long-term (2-year) incidence of TVR. METHODS AND RESULTS: We studied 234 patients in whom 1 or 2 stents were successfully deployed and ultrasound imaging performed after angiographic optimization. End points included a visually estimated angiographic residual stenosis <10% and ultrasound stent-to-mean reference lumen area > or = 80%. After 2 years, TVR was required in 48 (20.5%) patients. Qualitative predictors of TVR were vein graft lesions, 3-vessel disease, and baseline TIMI flow grade < 3. Quantitatively, reference diameter by quantitative coronary angiography (QCA), final minimum lumen diameter (MLD) by QCA, and in-stent minimum lumen area (MLA) by ultrasound were predictive of TVR. Stent-to-reference ratios were not significantly predictive of TVR. By multivariable analysis, vein graft location and MLA by ultrasound were the only significant predictors of TVR (relative risk, 2.9 [1.5, 5.4] and 0.72 [0.6, 0.9], respectively). Receiver operator curves for MLD by QCA and MLA by ultrasound were similar in predicting TVR. Neither was significantly superior to reference vessel diameter. CONCLUSIONS: Commonly used angiographic and ultrasound stent-to-reference ratios do not predict the incidence of TVR. Absolute measures of the lumen size (MLA by ultrasound and MLD by QCA) were the most important quantitative predictors of TVR within 2 years. This emphasizes the role of the vessel size as the limiting factor in determining the long-term outcome of coronary stenting.

Long-term vessel response to a self-expanding coronary stent: a serial volumetric intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent Ultrasound Remodeling Evaluation.

OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND: Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS: Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS: At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Intravascular ultrasound assessment of the prevalence and causes of angiographic "haziness" following high-pressure coronary stenting.

Haziness at sites of balloon angioplasty is believed to represent plaque fractures or platelet deposition. The etiology of haziness adjacent to coronary stents remains uncertain. This study examines the prevalence and etiology of "peri-stent" haziness following high-pressure deployment. Consecutive patients undergoing coronary stenting and intravascular ultrasound imaging were included. Haziness was defined as nonhomogeneous contrast density and/or indistinct vessel borders by consensus of 2 observers. Patients were excluded if angiography revealed an obvious cause of haziness (thrombus, dissection). Matched control segments without haziness were selected for comparison. The most diseased site within the reference segment was identified by ultrasound. Lumen and plaque areas, percent plaque area, and plaque echo density were assessed. Haziness was identified within 31 segments in 30 patients (15% of 201 angiograms examined). At hazy sites, ultrasound revealed a large percent plaque area in 15, dissections in 14, and near-normal findings in 2 segments. In the absence of dissection, percent plaque area and lumen area step-down from the stent to the diseased reference were greater than controls (percent plaque area 64 +/- 12% vs 56 +/- 10%, p = 0.04 and lumen step-down 35 +/- 20% vs 13 +/- 25%, p = 0.006). With dissections, percent plaque area and lumen step-down were not different from controls (p = 0.13 and 0.30, respectively), but underlying plaques were more frequently echolucent (64% vs 23%, p = 0.02). Thus, in this study, peri-stent haziness was evident in 15% of patients after high-pressure coronary stent deployment. Etiologies identified by intravascular ultrasound included unrecognized reference plaque and angiographically occult dissections.

The dilemma of diagnosing coronary calcification: angiography versus intravascular ultrasound.

OBJECTIVES: We sought to determine whether careful examination of angiograms in conjunction with other clinical information could reliably detect, quantitate and localize target lesion calcification before a coronary intervention. BACKGROUND: The presence, extent and location of calcium in coronary artery lesions are important determinants of outcome after coronary intervention. Intravascular ultrasound is proposed as a superior technique for identifying patients with coronary artery calcification. However, the precise role of this costly and invasive method has not yet been established. METHODS: Target lesion calcification was assessed in 183 patients (155 men; mean [+/-SD] age 58 +/- 10 years) by angiography and intravascular ultrasound before a planned percutaneous coronary intervention. RESULTS: Ultrasound detected calcium in 138 patients (>90 degrees in 56, 91 degrees to 180 degrees in 52, 181 degrees to 270 degrees in 22 and > 270 degrees in 8), whereas angiography showed calcification in 63 (1+ in 32, 2+ in 27 and 3+ in 4). The two techniques agreed in 92 patients and disagreed in 91. Sensitivity and specificity of angiography were 40% and 82%, respectively. The arc of calcium by ultrasound was greater in patients with angiographically visible calcification (175 degrees +/- 85 degrees vs. 108 degrees +/- 71 degrees, p=0.0001). The depth of calcification by ultrasound was superficial in 61 patients (44%), deep in 68 (49%) and mixed in 8 (7%). The sensitivity of angiography in identifying superficial calcium was 35%. Of 120 patients without angiographically visible calcium at the target lesion site, 83 showed calcium by ultrasound. The only predictor of ultrasound calcium in these 120 patients was angiographic calcification elsewhere in the coronary tree (p=0.0001). The probability of any calcium and superficial >90 degrees calcium were 60% and 12%, respectively, in the 90 patients without angiographic calcifications anywhere in the coronary tree. CONCLUSIONS: Despite poor sensitivity, angiography may help identify patients requiring intravascular ultrasound. When it is angiographically visible, the arc of calcium is likely to be large and superficial. Angiographic calcification at a remote site is a predictor of angiographically undetected target lesion calcium. Patients without angiographic calcification in the coronary tree may not need routine ultrasound examination, as the likelihood of >90 degrees superficial calcium is low.

Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: insights from systematic intravascular ultrasound imaging.

OBJECTIVE: The aim of this study was to evaluate the extent and distribution of coronary atherosclerosis after transplantation. BACKGROUND: Transplant coronary artery disease is an important cause of death after cardiac transplantation. Unlike coronary angiography, intravascular ultrasound is a sensitive tool for detection and quantitation of this disease. METHODS: We performed intravascular ultrasound imaging in 132 (106 men, 50 +/- 10 years) patients, 1 to 9 years after transplantation using a 30-MHz ultrasound catheter. RESULTS: All three coronary arteries were visualized in 49, two in 62 and one in 21 patients. Of the 1,188 coronary artery segments, 706 were imaged (74% proximal, 64% mid- and 40% distal). At least one site with atherosclerosis (intimal thickness > or = to 0.5 mm) was found in 83% of patients. Atherosclerosis was noted in 64% of proximal, 43% of mid- and 26% of distal segments. Disease was diffuse in 48% and focal in 52%, circumferential in 66% and noncircumferential in 34%. Focal atherosclerosis was more common in proximal (59%) than mid- (48%) and distal segments (27%) (p=0.001). Noncircumferential plaques were more common in the proximal (42%) than mid- (28%) and distal segments (12%) (p=0.001). This pattern of focal and noncircumferential disease proximally, diffuse and circumferential disease distally, was observed irrespective of the time from transplantation. CONCLUSION: Atherosclerosis was detected in more than 80% of patients, with proximal segments most frequently involved. Diffuse and circumferential atherosclerosis was more common in mid- and distal segments. However, focal and noncircumferential involvement was more frequent proximally, a similar pattern to native atherosclerosis. These findings suggest that transplant coronary artery disease has a dual etiology based on the dichotomous pattern of atherosclerosis seen by intravascular ultrasound.

Incremental value of intravascular ultrasound during rotational coronary atherectomy.

During the last several years, major improvements in intravascular ultrasound image quality have led to new and important information about the clinical application of rotational atherectomy. Ultrasound is providing data on the mechanism of luman enlargement, burr sizing, and the effects of the procedure on different plaque morphologies. This information is often important for optimizing device selection and procedural success, as well as for minimizing complications. In this review we first discuss the currently available data regarding the mechanisms of lumen enlargement following rotational ablation and the implications of these findings for lesion and patient selection. We review how this data is modifying several of the technical aspects of the rotational ablation procedure in the interventional laboratory. We than assess the available data that suggest that preprocedural ultrasound examination may eventually help to identify lesions at high risk for adverse outcome with stand-alone balloon angioplasty or stent placement. These ultrasound data may help triage many of these targets to initial debulking with rotational ablation. Finally, we review data that suggest that ultrasound analysis has important implications for comparative trials of new devices, particularly trials of the Rotabalator.

Coronary intravascular ultrasound: diagnostic and interventional applications.

Recent advances in microelectronic and piezoelectric technology have permitted development of miniaturized ultrasound devices capable of real-time tomographic intravascular imaging. Initial studies have successfully employed intravascular ultrasound to augment angiography in both diagnostic and therapeutic catheterization. The cross-sectional perspective of intravascular ultrasound appears to be ideally suited for precision measurements of luminal diameter and cross-sectional area. In addition, ultrasound improves assessment of problem lesions such as ostial stenoses or disease at bifurcations. Intravascular imaging provides unique, detailed cross-sectional images of the arterial wall not previously obtainable in vivo by any other technique and is more sensitive than angiography in detecting atherosclerosis. Intravascular ultrasound images of atherosclerotic wall abnormalities have the potential to augment greatly the understanding of the anatomy and pathophysiology of coronary disease. For interventional applications, ultrasound analysis of lesion characteristics offers many potential advantages. Evaluation of the normal reference segment used for device sizing constitutes an important emerging application for intravascular imaging. After the procedure, intravascular ultrasound often yields smaller luminal size measurements than angiography and greater of stenosis. These differences probably reflect augmentation of the apparent angiographic diameter by extraluminal contrast within cracks, fissures or dissection planes. New ultrasound instruments under development combine an imaging transducer with an interventional device, permitting on-line guidance during the procedure. Although the clinical value of routine ultrasound imaging before or after mechanical revascularization has not been tested by randomized trials, it seems likely that this new imaging modality will provide valuable insights into diverse phenomena such as abrupt occlusion and restenosis. Accordingly, we anticipate a continuing role for this modality in cardiovascular interventional therapy.

Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation. Insights from intravascular ultrasound.

BACKGROUND: Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy. METHODS AND RESULTS: We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53 +/- 9 years) 4.6 +/- 2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32 +/- 12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness > or = 0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3 +/- 0.6 mm and the cross-sectional area narrowing was 34 +/- 16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87 +/- 8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37 +/- 12 versus 25 +/- 10 years, P = .001). Maximal intimal thickness correlated with donor age (r = .54, P = .0001). Multivariate analysis demonstrated that donor age (P = .0001), male sex of donor (P = .0006), and recipient age (P = .03) were independent predictors of atherosclerosis. CONCLUSIONS: Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.