Eccentric Plaque Research Articles

Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction.

Ischemic heart disease includes a wide spectrum of conditions, ranging from silent ischemia and exertion-induced angina, through unstable angina, to acute MI. Unstable angina occupies the center of this spectrum, causing disability and risk greater than that of chronic stable angina but less than that of acute MI1 (Fig 1⇓). Although non–Q-wave MI for many years was considered prognostically similar to unstable angina, recent longitudinal studies indicate that it is similar to Q-wave infarction2 3 (Fig 2⇓). Figure 1. Cumulative 6-month mortality from ischemic heart disease. Diagnosis on admission to hospital (n=21 761; 1985 to 1992). From Duke Cardiovascular Database. Reproduced with permission from Reference 1. Figure 2. Top, Cumulative 1-year combined death or MI among patients with Q-wave and non–Q-wave MI treated with fibrinolysis. Reproduced with permission from Reference 2. Bottom, Risk of subsequent cardiac events in stable convalescing patients after first non–Q-wave and Q-wave MI. Reproduced with permission from Reference 3. The concept of unstable angina has emerged from observations of frequent symptoms preceding acute MI, followed by prospective documentation that unstable symptoms frequently culminated in acute MI. The syndrome was rapidly accepted as a well-defined clinical entity as specific clinical manifestations, pathophysiological mechanisms, laboratory findings, and treatment became better characterized. Unstable angina is currently one of the leading causes of hospital admission for CAD, and non–Q-wave MI accounts for >30% of admissions for acute MI.1 4 Yet, the diagnosis of unstable angina remains clinical, based on symptom recognition. The physician caring for patients with unstable angina is in a privileged position of recognizing rapidly evolving CAD and being able to intervene to prevent irreversible left ventricular damage and progression of CAD. Unstable angina is classically described as a heterogeneous disease, referring to a wide spectrum of clinical manifestations from stable angina to MI, of disease …

Highly localized arterial remodeling in patients with coronary atherosclerosis: an intravascular ultrasound study.

Preservation of luminal area and symmetry in the presence of irregular plaques necessitates local expansion of the artery wall. Cross-sectional dimensions of coronary arteries in 65 patients were measured with the use of intravascular ultrasound. A total of 104 arterial segments were studied, of which 88 had atherosclerosis; 16 served as nonatherosclerotic control segments. Three features of atherosclerotic arterial segments were classified: (1) plaque formation, (2) lumen shape, and (3) shape of arterial external elastic lamina. With our intravascular ultrasound-based three-level classification system, we identified three patterns that accounted for 89% of all atherosclerotic arterial segments: (1) concentric plaque with a circular lumen and a circular external elastic lamina (n= 17), (2) eccentric plaque with a circular lumen and an oval external elastic lamina (n=35), and (3) eccentric plaque with an oval lumen and a circular external elastic lamina (n=26). A circular lumen was preserved in 66% of all atherosclerotic arterial segments. Arterial segments with a circular lumen in the presence of an eccentric plaque had a significantly larger lumen area than the other two main groups (P<.05). With our intravascular ultrasound-based classification, we provided information regarding the local remodeling response in the coronary artery wall. In a majority of cases, a circular lumen is maintained. Failure of this highly localized response to be operative may contribute to the development of stenotic lesions at a specific site in the artery.

Comparison of Men Versus Women in Cross-Sectional Area Luminal Narrowing, Quantity of Plaque, Presence of Calcium in Plaque, and Lumen Location in Coronary Arteries by Intravascular Ultrasound in Patients with Stable Angina Pectoris

Women have an increased mortality after coronary interventions compared with men, which may be partly explained by differences in comorbid clinical conditions. However, whether women also have quantitative differences in coronary atherosclerosis is not known. Preinterventional intravascular ultrasound (IVUS) was used to study de novo, nonostial native coronary lesions in 169 women and 549 men with chronic angina. The external elastic membrane (EEM), lumen, and plaque + media (P + M) areas, plaque burden, plaque eccentricity, and calcium were measured at the target lesion and at a proximal reference site. All cross-sectional IVUS measures were also corrected for body surface area. Results are reported as mean ± 1 SD. Women had significantly smaller reference site EEM (16.5 ± 5.3 vs 19.4 ± 6.3 mm2, p <0.0001), lumen (8.7 ± 3.0 vs 9.9 ± 4.0 mm2, p = 0.0020), and P + M areas (7.8 ± 3.7 vs 9.5 ± 4.2 mm2, p = 0.0001). Women also had significantly smaller lesion site EEM (16.2 ± 5.9 vs 18.3 ± 6.7 mm2, p = 0.0028), lumen (2.4 ± 1.7 vs 2.9 ± 2.6 mm2, p = 0.0273), and P + M areas (13.6 ± 5.7 vs 15.3 ± 6.4 mm2, p = 0.0112). However, when corrected for BSA, these differences were no longer significant. Women and men also had similar reference and lesion plaque burden, eccentricity, and calcium. Preinterventional IVUS analysis failed to detect any quantitative or qualitative differences in coronary atherosclerosis in men compared with women.To determine whether there are quantitative differences in coronary atherosclerosis in men compared with women, preinterventional intravascular ultrasound (IVUS) was used to study de novo, nonostial native vessel lesions in 169 women and 549 men with chronic angina. Women had significantly smaller reference segment and target lesion external elastic membrane, lumen, and plaque cross-sectional areas; however, when corrected for body surface area, these differences were no longer significant. Women and men also had similar reference segment and target lesion plaque burden, eccentricity, and calcification. Preinterventional IVUS analysis failed to detect any quantitative differences in coronary atherosclerosis in men compared with women.

Histological and Immunohistochemical Characteristics of Eccentric Coronary Artery Lesions Retrieved by Atherectomy from Cardiac Transplant Recipients

The lesions of cardiac allograft vasculopathy are thought to be strongly related to an immune inflammatory process. Little is known about the biology of these eccentric lesions. However, transplant patients may present with focal disease. Coronary atherectomy provides a unique opportunity to study these clinically relevant lesions in surviving transplant patients. In this series we characterized the features of four lesions (two restenotic and two primary) from three cardiac transplant recipients who underwent coronary atherectomy. The histologic characteristics of the lesions were analyzed and immunohistochemistry was used to assess qualitatively the presence of specific markers of inflammation and the extracellular matrix component fibronectin. Histology showed cholesterol clefts, calcium deposits, and foam cells with low to moderate cellularity and moderate to high fibrosis. Interleukin (IL)-1β was present in two lesions, but tumor necrosis factor (TNF)-α was absent. The adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cellular adhesion molecule (VCAM)-1 and the integrins α5β1 and α4 were present in all lesions. There was mild to moderate accumulation of fibronectin. Thus, atheroscleroticlike features were present with only low to moderate degrees of immune inflammation. Our findings suggest that eccentric focal plaques in cardiac allograft vasculopathy are less likely to be primarily related to a prominent immune inflammatory process and are similar to atherosclerosis. We speculate that these eccentric lesions that resemble atherosclerosis may be more related to the conventional risk factors for coronary artery disease frequently seen in this population.

Coronary plaque morphologic characteristics early and late after heart transplantation: In vivo analysis with intravascular ultrasonography

To characterize plaque morphologic characteristics of transplant coronary artery disease early and late after cardiac transplantation, 72 patients were studied with intravascular ultrasonography during routine coronary angiography (group 1, 25 patients ≤2 months after surgery; group 2, 47 patients ≥12 months after surgery). Both groups had comparable baseline characteristics. Three hundred fifty-one segments were imaged in 127 coronary arteries (4.9 ± 1.8 segments per patient). By intravascular ultrasonography, relevant intimal thickening (>0.3 mm) was found in the majority of patients (68% for group 1 and 72% for group 2). Angiography detected abnormal findings in only 16% and 32% for groups 1 and 2, respectively. Mean intimal index was higher in patients late after transplantation (27% ± 12% vs 17% ± 12%, respectively; p < 0.01). Maximal and mean plaque thickness were comparable in both groups, whereas a higher mean plaque circumference was found in group2 (278 ± 66 degrees vs 211 ± 75 degrees, respectively; p < 0.002). The lesions were more eccentric in patients early after transplantation (mean eccentricity index 95% ± 7% vs 77% ± 15%, respectively; p < 0.0001). Diffuse, concentric intimal thickening was not a common pattern. Maximal plaque thickness correlated with donor age ( r = 0.50, p < 0.0001). Coronary lesions were frequent even early after transplantation, with predominantly eccentric plaque morphologic characteristics indicative of preexisting atherosclerosis. Later after transplantation, a more homogeneous plaque distribution was seen, partly with diffuse concentic intimal thickening. Late transplant coronary artery disease appears to be a combination of preexisting native and acquired immune-mediated coronary artery disease. (Am Heart J 1997;133:29-35.)

In SituMaterial Transformations in Tissue Engineering

Novel applications exist for biomedical materials that can undergo transitions in material propertiesin situ—that is, at the site of implantation in the body. Such transitions in polymeric biomaterials can be accomplished by crosslinking a materialin situ, by heating or cooling to induce thermal transitions, and by precipitating polymer from solutionin situ. This article will point out the need for materials that can be induced to undergo such transitions in situ and will describe selected tissue-engineering approaches that have been employed for this purpose.Delivering materials to the body in one form and utilizing them in another form after a transition at the site of implantation has, generally speaking, two potential advantages: (1) the ability to match the morphology of a material implant to a complex tissue shape and (2) the ability to deliver a large device through a small hole in the body. With respect to the former motivation, tissue shapes in the body have an enormous range of complexity: a region of a blood vessel—for example with a curved central axis, a diameter that varies along the length, an eccentric diseased plaque, and numerous side branches. One could develop a variety of implant shapes—arterial stents in this example (for use in structurally supporting arteries after balloon angioplasty, thereby creating a larger cross section for blood flow above the diseased plaque)—and then select the most appropriate implant shape after detailed imaging of the tissue site. One can alternatively attempt to employ some material transformation to deliver a precursor to the final shape of the implant, utilizing the tissue shape to obtain the proper final implant morphology. With regard to the second motivation, it may be desirable to deliver a large object through a small hole, utilizing material transformations. Advances in surgery have focused on manipulating (cutting, coagulating, suturing, stapling) large tissue sites through small holes in the body via minimally invasive surgery. Using such approaches, it has become possible to perform many complex surgical procedures in the joints, abdominopelvic cavity, thoracic cavity, and nasal sinuses, for example, using surgical instruments that are manipulated through surgical access holes less than 1 cm in diameter. Even procedures as complex as coronary-artery bypass surgery have been performed in this way. It still remains generally impossible however to implant devices in the body through such holes unless these implants are very small. If such devices were for example able to be delivered as liquids and then shaped into devices at the implant site, such minimally invasive surgical-device placement could be envisioned.

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: Correlation with high density lipoproteins

Objectives. This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultraound imaging.Background. Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis.Methods. Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque.Results. Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [±SD] 0.25 ± 0.16) than in the left main (0.11 ± 0.16, p < 0.001) and iliac arteries (0.02 ± 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index ⪰0.42 (left anterior descending artery) and ⪰0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery.Conclusions. In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Coronary stenting with a novel stainless steel balloon-expandable stent: Determinants of neointimal formation and changes in arterial geometry after placement in an atherosclerotic model

This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis. The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized. We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement. Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 +/- 0.09 mm (reference diameter 2.87 +/- 0.06 mm, mean +/- SE) and increased to 2.82 +/- 0.05 mm (p < 0.001) after stent placement. The balloon-inflated stent diameter was 2.98 +/- 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 +/- 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 +/- 0.01 vs. 0.27 +/- 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 +/- 0.27 vs. 2.68 +/- 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 +/- 0.34 mm2) than nonstented atherosclerotic vessels (0.44 +/- 0.28 mm2, p = 0.033). Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.

Influence of plaque composition on mechanisms of percutaneous transluminal coronary balloon angioplasty assessed by ultrasound imaging

In this study the influence of plaque composition on mechanism of immediate lumen enlargement after PTCA were assessed by serial ultrasound imaging in 77 patients. According to the preprocedural ultrasonic plaque characteristics, the lesions were classified as soft (54.5%), diffusely calcified (14.3%), and mixed (31.2%). The total arc of calcium and plaque eccentricity were also calculated. The mean balloon/artery ratio was equal for all types of lesions (1.07 ± 0.19), but diffusely calcified lesions required a higher maximal balloon inflation pressure (11.3 ± 3.75 atm vs 9.0 ± 3.15 atm for calcified and soft lesions, respectively, p < 0.05). The increase in lumen area after PTCA was similar in soft and mixed lesions (3.49 ± 1.61 mm 2 vs 3.56 ± 1.58 mm 2, NS) and was slightly lower in diffusely calcified lesions (2.97 ± 1.33 mm 2, NS). Reduction in plaque area was the main operative mechanism in lesions with soft plaque, explaining 77.9% of the acute lumen gain. Expansion of the total vessel area was the predominant mechanism of lumen area increase in lesions with calcified and mixed plaques (99.1% vs 74.2%, respectively, NS). In particular, lesions with a total arc of calcium >90 degrees showed a high prevalence of vessel expansion as a mechanism of lumen enlargement compared with lesions with a calcium arc <90° (79.3% vs 23.8%, respectively, p < 0.05). In the studied group, presence of calcification was highly associated with wall fracture and dissection after balloon dilatation (93.4% vs 6.6% in lesions with and without calcifications, respectively, p < 0.05). A trend toward a greater degree of plaque reduction in concentric lesions in comparison to eccentric lesions was observed (58.3% vs 48.5%, respectively, NS). In conclusion, immediate lumen enlargement after PTCA does not differ for soft and mixed plaques. Diffusely calcific plaques show a smaller lumen enlargement despite a higher balloon inflation pressure. Plaque compression or axial redistribution is the main operative mechanism of PTCA in soft plaques, whereas an increase in total vessel area determines the lumen enlargement in mixed/calcific plaques. Plaque fracture or wall dissection is almost invariably associated with presence of plaque calcification.

Influence of plaque composition on luminal gain after balloon angioplasty, directional atherectomy, and coronary stenting

This study was conducted to correlate the acute luminal enlargement achieved by three different nonsurgical revascularization procedures in 79 patients (32 treated by balloon angioplasty, 29 by directional atherectomy, and 18 by coronary stenting) with the morphologic characteristics of coronary plaques assessed by preprocedure intravascular ultrasound. The absolute luminal gain was 2.41 ± 1.54 mm 2 for balloon angioplasty, 3.17 ± 1.8 mm 2 for directional atherectomy, and 4.56 ± 1.45 mm 2 for coronary stenting ( p = 0.00005). However, when luminal gain was corrected for the external vessel area (luminal gain index), such difference was no longer present (0.22 ± 0.12 for balloon angioplasty, 0.24 ± 0.15 for directional atherectomy, and 0.30 ± 0.12 for coronary stenting, p = not significant). Concentric plaques treated by coronary stenting had a higher luminal gain index than eccentric plaques ( p = 0.01). A comparison of the three devices showed that a similar luminal gain index was achieved in soft plaques, whereas coronary stenting was superior to directional atherectomy (0.41 ± 0.10 vs 0.20 ± 0.09, p = 0.002) and balloon angioplasty (0.41 ± 0.10 vs 0.19 ± 0.08, p = 0.0005) in concentric plaques. Coronary stenting also induced a greater luminal gain index than directional atherectomy in calcific plaques (0.30 ± 0.11 vs 0.18 ± 0.09, p = 0.04). In conclusion, these data show that plaque morphology assessed by preprocedure intracoronary ultrasound influences the acute luminal enlargement achieved by different coronary interventions. The knowledge of plaque composition may be useful in guiding the choice of the device to be used to obtain a larger acute luminal gain.

Coronary artery spasm: Multiple causes and multiple roles in heart disease

Myocardial infarction and sudden cardiac death may be initiated by a sudden intense localized contraction of coronary artery smooth muscle. When this event occurs around a vulnerable eccentric lipid-filled plaque, rupture and extrusion of plaque contents and exposure of collagen occur. This may sometimes be a silent and self-limiting event; other times it leads to thrombus formation. A second wave of spasm due to accumulated platelet and inflammatory mediators may compound the contractile consequences of the initiating event. Spasm involves intrinsic smooth muscle cell electrical mechanisms, hyper-responsive cells, and multiple agonists that synergize their actions, and the involvement of each mechanism varies at different times in the sequence of vascular occlusion. Study of spasm requires vascular systems that adequately model coronary artery responses of the ageing human heart. As previously emphasized, tissues obtained postmortem, and when possible from recipients during heart transplants, must be integral to theory building, alongside animal models, despite the experimental limitations such tissues impose. A multidisciplinary approach, at all levels of vascular physiology and pharmacology, will be necessary to understand coronary motor activity and human heart disease.

Management of vasospastic angina--role of nicorandil.

Clinical and experimental observations have confirmed that an episodic increase in the vasomotor tone of a major coronary artery may play a pathogenetic role not only in "variant angina" but also in other, more common anginal syndromes. In chronic stable angina, dynamic changes of vascular smooth muscle tone at the site of eccentric atheromatous plaques are responsible for "mixed angina." Abnormal coronary vasomotion contributes to myocardial ischemia in acute coronary syndromes as well. Studies have shown that a "primary" reduction of coronary blood flow, usually associated with plaque fissuring and thrombus formation, causes infarction and unstable angina. Abnormal vasoconstriction associated with the release of vasoactive substances by platelets and other constituents of the thrombus can contribute to coronary flow reduction in patients with unstable angina and myocardial infarction. Better understanding of the complex interactions among atherosclerotic coronary obstructions, the vascular smooth muscle, and the vascular endothelium has resulted in novel therapeutic approaches and has stimulated the search for more efficacious and safer coronary vasodilators. Recently interest has focused on vasodilator agents such as nicorandil that influence coronary arterial tone by acting through potassium channel activation. Nicorandil appears to be effective for treatment of vasospastic angina, as suggested by studies in Japan and Europe. In addition to its "antivasospastic" properties, nicorandil dilates coronary artery stenoses in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

797-5 Ulceration of Smooth Muscle Cell-Rich Plaques: A Frequent Cause of Coronary Artery Thrombosis That is not Mediated by HLA-DR Expression

Coronary artery thrombosis (CAT) is reported to occur primarily from plaque rupture (PRI involving disruption of a fibrous cap over a necrotic core. However, CAT associated with superficial ulceration ISUI of predominately fibromuscular plaques without rupture of a necrotic core is under-reported. We performed post-mortem angiography, detailed coronary histology, morphometry, and immunohistochemistry in 42 cases (33 men, 9 women) of sudden death due to CAT. All individuals died ≤6 hours of symptom onset. Histo- and immunochemical stains consisted of Movat pentachrome, H&amp;E, smooth muscle specific actin, KP-1 (for macrophages). UCHL1 (for T-cells), Leder stain Ifor neutrophils). and HLA-DR. Age (yr) SMCs MACs T-cells PMNs NC CAL PR, n = 24 52 ± 10 8% 67% 100% 8% 83% 71% SU, n = 18 44 ± 7 61% 22% 36% 28% 33% 28% p-value &lt;0.02 &lt;0.001 &lt;0.01 &lt;0.005 0.12 &lt;0.01 &lt;0.02 SMCs ( = smooth muscle cells), MACs ( = macrophages), T-cells, and PMNs ( = neutrophils) in plaque adjacent to thrombus: NC = large necrotic core; CAL = calcified plaque The luminal surface of SU plaques contained accumulations of SMCs within a proteoglycan matrix. In PR cases, the ruptured fibrous cap was typically infiltrated by MACs and T-cells. Expression of HLA-DR antigens was present in MACs and T-cells in 62% of PR cases and expressed in SMCs in 14% of SU cases (p &lt; 0.02). The percent luminal area stenosis was 79 ± 13% in PR and 71 ± 14% in SU, p &lt; 0.05. No differences in plaque eccentricity or occlusive vs. non-occlusive thrombi were noted. Superficial ulceration of smooth muscle cell-rich plaques lacking plaque rupture into a large necrotic core is a frequent (43%) finding in coronary thrombosis and is more often seen in younger persons with non-calcified plaques and less luminal narrowing. The mechanism of coronary artery thrombosis in plaques rich in SMCs is not mediated by HLA-DR expression and warrants further study.

730-3 “Directional” Coronary Atherectomy Removes Atheroma More Effectively from Concentric than Eccentric Lesions: Intravascular Ultrasound Predictors of Lesional Success

Directional coronary atherectomy (DCA) was developed to remove atheroma from eccentric lesions. Conventional teaching proposes that DCA is most effective for eccentric plaques; however, no data have correlated plaque configuration with atheroma removal. We performed intravascular ultrasound and angiography to assess the effect of plaque distribution and morphology on acute lesional success (percentage of plaque removed). We examined 101 target lesions and reference sites in 88 patients pre-and post-atherectomy. A core laboratory, blinded to outcome, classified lesions as concentric if plaque exceeded 0.75 mm in thickness for the entire 360° vessel circumference. Lesions with sparing of a portion of the vessel circumference (minimum plaque thickness &lt; 0.75 mm) were classified as eccentric. Other variables quantified by ultrasound included the presence and arc (in degrees) of vessel wall calcification. Angiographic lesion eccentricity and/or calcification did not correlate with percentage of plaque removed. The presence of ultrasound calcium decreased the percentage of plaque removed from 24.2% to 13.6%, p = 0.05. The arc of ultrasound calcification correlated inversely with plaque removal, r = 0.55. Most importantly: Ultrasound Plaque Distribution Concentric Lesions Eccentric Lesions p value Plaque Removed (mm 2 ) 4.66 2.43 0.003 Plaque Removed (%) 29.9 18.7 0.02 Adjunctive Balloon 56% 81% 0.05 Contrary to current doctrine, atherectomy achieves better plaque removal and requires adjunctive balloon less often in lesions with concentric, rather than eccentric, atheromata. Ultrasound target lesion calcification is a negative predictor of plaque removal.

Assessment of the reliability of the determination of carotid artery lumen sizes by quantitative image processing of magnetic resonance angiograms and images

In order to use MR imaging to assess progression or regression of atherosclerosis, one must have an idea of the reproducibility of the imaging and image processing techniques. The ability of dark-blood MRI and semiautomated image processing to reproducibility measure the inner boundary of the carotid arteries was evaluated and compared with results obtained using bright-blood MRA. MRI and MRA images were obtained for two normal and two diseased volunteers six times each over a short period of time (6 months). The carotid bifurcation was used to align slices from different imaging sessions. The area for each vessel (right and left common, internal and external carotid artery) was determined for the six imaging sessions. The standard deviations of each lumen area normalized to the average area were computed for each vessel segment for each volunteer. For the common, internal, and external carotids, the averaged normalized standard deviations for MRI were 8, 12, and 17% and for MRA were 6, 8, and 13%. Lumen sizes obtained by MRI and MRA were found to be not statistically different. Eccentric plaques not seen on MRA were visualized by MRI. In conclusion, dark-blood MRI with semiautomated image processing yields reliable lumen areas that are in agreement with those obtained by MRA.

Directional atherectomy of left main stenoses.

Balloon angioplasty (PTCA) of left main (LM) stenoses is limited by frequent clinical restenosis. Directional coronary atherectomy (DCA) may be an effective alternative to PTCA due to its ability to achieve a greater postprocedural luminal diameter when treating bulky, eccentric plaques and aorto-ostial lesions. We analyzed the acute and long-term results following 24 DCA procedures in 22 patients with "protected" LM lesions. Acute success (residual stenosis < or = 40%, no major ischemic complications) was 88% overall, 100% in 13 planned procedures, and 73% in 11 adjunctive DCA procedures that followed suboptimal PTCA. Mean LM stenosis was reduced from 86% to 13% (P < 0.01). There were no procedural complications directly attributed to DCA. At a mean of 24 +/- 3 months, the clinical restenosis rate was 16%, survival was 100%, and event-free survival (freedom from death, MI, or repeat lesion-related interventions) was 89%. We conclude that DCA in protected LM lesions (1) can achieved excellent angiographic results with low procedural complication rates, (2) may succeed where PTCA yields suboptimal results, and (3) may provide late clinical outcomes superior to those of balloon angioplasty.

Lumen and plaque shape in atherosclerotic coronary arteries assessed by in vivo intracoronary ultrasound

Current knowledge of lumen and plaque shape of atherosclerotic coronary vessels is derived from in vitro examination of coronary vessels. The in vivo plaque and lumen shape was studied by intracoronary ultrasound (ICUS) imaging in 82 patients with coronary artery disease and the images were analyzed by computerized morphometry. In 386 of the 638 cross sections (61%) with atherosclerotic plaque, nondiseased wall (intima thickness <200 μm) was present in the ICUS image; in 440 sections (69%), the plaque was located eccentrically in the vessel. Although the extent of nondiseased wall segment and eccentricity decreased with plaque burden, 42% of cross sections with plaque stenosis >60% had residual nondiseased wall, and 40% of these cross sections showed eccentric plaque. A circular or near-circular lumen (ratio of long/short diameter <1.1) was found in 252 cross sections (39%), an elliptical lumen in 370 (58%), and a “D”-shaped lumen in 16 cross sections (3%); slit- or star-like lumen shapes were not detected. The ratio of long/short diameter was lower in the 555 noncalcified (1.10 ± 0.08) than in the 83 calcified cross sections (1.15 ± 0.08; p < 0.001). Radiographic lumen area measurements were simulated in ellipse models based on the long and short lumen axes measured in the ICUS images. Assuming a single radiographic view, maximal over- or underestimation of up to 40% compared with the true vessel lumen is possible. Errors in lumen area measurements increased with plaque area stenosis, reflecting the more elliptical lumen shape in advanced coronary disease. When biplane orthogonal views on the lumen silhouette are used, the maximal error for lumen area measurements occurs at a 45° angle to the long lumen axis. In all cross sections, the maximal error for lumen area measurements with biplane radiographic views resulted in an error <10% as compared with true vessel lumen. Thus, the present in vivo observations confirm previous histologic findings that eccentric plaque and residual nondiseased wall may be found even in advanced coronary atherosclerosis. In contrast to histologic findings, the lumen shape of atherosclerotic coronary vessels deviates only moderately from a circular lumen. Radiographic lumen area measurements in coronary vessels are therefore only slightly affected by different lumen shapes when biplane views are used.

Predictors of restenosis: A morphometric and quantitative evaluation by intravascular ultrasound

Despite advances in catheter-based interventional techniques, restenosis remains a major complication of angioplasty. Recently, intravascular ultrasound imaging (IVUS) has provided new insight into plaque composition and geometric distribution inside the vessel. To investigate if IVUS-defined parameters can predict restenosis in patients after coronary angioplasty, we performed IVUS in 33 patients (33 lesions) after balloon angioplasty ( n = 25) or directional atherectomy ( n = 8). Qualitative analysis included assessment of plaque composition, plaque eccentricity, plaque fracture, and presence of dissection. In addition, minimal luminal diameter, percent diameter stenosis, percent area stenosis, plaque burden, and elastic recoil were quantitatively analyzed. Follow-up data were obtained 1, 2, and 6 months after angioplasty and were available for 30 patients. Angiographic restenosis occurred in 11 patients (group 1), and no restenosis occurred in 19 patients (group 2) by clinical ( n = 10) or angiographic ( n = 9) assessment. Plaque fracture was noted in 30% of group 1 patients and 74% of group 2 patients ( p = 0.04). Major dissections were more frequent in group I than in group II (78% vs 10%, p = 0.009). Of the quantitative parameters analyzed, plaque burden was significantly higher in group 1 than in group 2 (0.50 ± 0.05 vs 0.34 ± 0.05, p = 0.0001). In 78% of the patients with plaque burden of > 0.40, restenosis developed. Thus, of the various parameters analyzed, the absence of plaque fracture, the existence of a major dissection, and greater plaque burden were associated with increased incidence of restenosis. Our results indicate that IVUS can identify a subset of patients in whom restenosis is likely to develop. Information about the morphologic features of the atheroma and its composition may be used to modify the interventional strategy and thus optimize lumen size and possibly reduce the chance of restenosis.

Intracoronary ultrasound imaging: Intraobserver and interobserver variability of morphometric measurements

Measurements of lumen and plaque dimensions by intracoronary ultrasound imaging are useful in assessing effects of intracoronary interventions and in quantifying plaque burden in transplant patients or during regression trials. However, these measurements are affected by inter- and intraobserver variability. In 87 patients, 120 intracoronary ultrasound images were obtained with a 4.3F, 30 MHz catheter. Morphometric measurements were performed two times by three independent observers using computerized planimetry. Intraobserver and interobserver agreement for qualitative parameters (presence of atherosclerotic plaque, calcified plaque, and residual nondiseased wall) was high (>87%). For quantitative parameters measured directly in the images (lumen area, minimal and maximal lumen diameters, area within the internal elastic lamina, arc of calcium plaque) interobserver and intraobserver correlation between measurements was high (correlation coefficient r > 0.90) and differences between measurements were low (mean differences <10%; SD <20%). Measurement of the arc of nondiseased wall showed less interobserver correlation ( r = 0.76 to 0.91), but percentages of difference between the measurements were low. Parameters derived from directly measured variables (plaque area, area stenosis, thickness, and eccentricity) showed slightly higher variability (correlations between measurements r = 0.78 to 0.91). SD for percentages of difference ranged between 20% and 30% (plaque area, area stenosis, and thickness) and systematic deviation between measurements (mean differences >10%) occurred for plaque area. Thus most qualitative and quantitative measurements of lumen and plaque dimensions performed in intracoronary ultrasound images have low intraobserver and interobserver variability; derived parameters may have slightly higher variability. Variability of morphometric measurements has to be considered, especially when serial ultrasound measurements are compared.

Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study

Objectives. The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease.Background. Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance.Methods. Twenty-seven patients (mean age [±SD] 57 ± 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 dilferent coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (ΔA) and pressure (ΔP) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [ΔA/AJ/ΔP [mm Hg−1×x 103]).Results. Lumen area and plaque area were 12.6 ± 5.7 and 3 ± 3 mm2, respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = −0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 ± 2.1 vs. 1.8 ± 1.2 mm Hg−1, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 ± 1.9 vs. 1.6 ± 1.1 mm Hg−1, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 ± 9.7 vs. 2.3 ± 1.6 mm Hg−1, p < 0.01) but was similar in concentric and eccentric plaques (1.6 ± 1.5 vs. 1.6 ± 0.9 mm Hg−1). Plaque area (r = − 0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance.Conclusions. Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.