Lesion External Elastic Membrane Research Articles

Association of culprit lesion plaque characteristics with flow restoration post-fibrinolysis in ST-segment elevation myocardial infarction: an intravascular ultrasound-virtual histology study

BackgroundNot every patient achieves normal coronary flow following fibrinolysis in STEMI (ST-segment elevation myocardial infarction). The culprit lesion plaque characteristics play a prominent role in the coronary flow before and during percutaneous coronary intervention. The main purpose was to determine the culprit lesion plaque features by virtual histology-intravascular ultrasound (VH-IVUS) in patients with STEMI following fibrinolysis in relation to baseline coronary angiogram TIMI (thrombolysis in myocardial infarction) flow. Pre-intervention IVUS was undertaken in 61 patients with STEMI after successful fibrinolysis. After the coronary angiogram, they were separated into the TIMI1–2 flow group (n = 31) and TIMI 3 flow group (n = 30). Culprit lesion plaque composition was evaluated by VH-IVUS.ResultsOn gray-scale IVUS, the lesion external elastic membrane cross-sectional area (EEM CSA) was significantly higher in the TIMI 1–2 groups as compared to the TIMI 3 group (15.71 ± 3.73 mm2 vs 13.91 ± 2.94 mm2, p = 0.041) with no significant difference in plaque burden (82.42% vs. 81.65%, p = 0.306) and plaque volume (108.3 mm3 vs. 94.3 mm3, p = 0.194). On VH-IVUS, at the minimal luminal area site (MLS), the fibrous area (5.83 mm2 vs. 4.37 mm2, p = 0.024), necrotic core (NC) area (0.95 mm2 vs. 0.59 mm2, p < 0.001), and NC percentage (11% vs. 7.1%, p = 0.024) were higher in the TIMI 1–2 groups in contrast to the TIMI 3 group. The absolute necrotic core (NC) volume (8.3 mm3 vs. 3.65 mm3, p < 0.001) and NC percentage (9.3% vs. 6.0%, p = 0.007) were significantly higher in the TIMI 1–2 groups as compared to the TIMI 3 group. Absolute dense calcium (DC) volume was higher in TIMI 1–2 groups with a trend towards significance (1.0 mm3 vs.0.75 mm3, p = 0.051). In multivariate analysis, absolute NC volume was the only independent predictor of TIMI 1–2 flow (odds ratio = 1.561; 95% CI 1.202–2.026, p = 0.001). Receiver operating characteristic curves showed absolute NC volume has best diagnostic accuracy (AUC = 0.816, p < 0.001) to predict TIMI 1–2 flow with an optimal cutoff value of 4.5 mm3 with sensitivity and specificity of 79% and 61%, respectively.ConclusionsThis study exemplifies that the necrotic core component of the culprit lesion plaque in STEMI is associated with the coronary flow after fibrinolysis. The absolute necrotic core volume is a key determinant of flow restoration post-fibrinolysis and aids in prognostication of less than TIMI 3 flow.

Impact of plaque burden and composition on coronary slow flow in ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: intravascular ultrasound and virtual histology analysis

Aim Coronary slow flow (SF) is an important complication of percutaneous coronary intervention (PCI) associated with poor prognosis. The aim was to assess grey-scale intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) characteristics of culprit lesion in ST-elevation myocardial infarction (STEMI). Methods A total of 295 consecutive patients with STEMI underwent coronary angiogram and IVUS. Following PCI, patients divided into two groups; SF (thrombolysis in myocardial infarction [TIMI] flow ≤ 2, n = 74) and normal flow (NF) (TIMI flow >2, n = 221). Coronary plaque burden and its composition in relation to SF were evaluated. Results On grey-scale IVUS, the plaque area (12.3 mm2 vs. 11.5 mm2, p = .01), plaque volume (110.7 mm3 vs. 99.8 mm3, p < .001), lesion external elastic membrane (EEM) cross-sectional area (14.9 mm2 vs. 14.0 mm2, p = .011) and remodelling index (1.3 vs. 1.2, p = .043) were significantly higher in SF group. On VH-IVUS, absolute fibrous volume (48.1 mm3 vs. 41.5 mm3, p ≤ .001), fibrofatty volume (23.8 mm3 vs. 18.6 mm3, p = .015), necrotic core volume (8.3 mm3 vs. 5.5 mm3, p < .001), dense calcium volume (1.2 mm3 vs. 0.6 mm3, p = .003) and thin cap fibroatheroma either single (30.1% vs. 16.1%, p < .001) or multiple (9.6% vs. 1.8%, p < .001) were higher in SF arm. In multivariable analysis, absolute necrotic core volume (odds ratio = 1.159; 95% CI 1.030–1.305, p = .015) was the only independent predictor of SF. Conclusions Higher necrotic core volume as detected by VH-IVUS may be a potential risk factor for the development of coronary SF phenomenon in patients with STEMI after PCI.

A new intravascular ultrasound-guided stenting strategy compared with angiography on stent expansion and procedural outcomes in patients with positive lesion remodeling.

We investigated the role of a new intravascular ultrasound (IVUS)-guided stenting strategy versus angiography on optimal stent expansion (OSE) and procedural outcomes in patients with positive lesion remodeling. There are no IVUS criteria on how to achieve OSE. A total of 100 patients were assigned to a new IVUS-guided stenting strategy (IVUS group) versus angiography-guided stenting (Angio group). In the IVUS group, among patients with positive lesion remodeling, defined as a remodeling ratio (RR; lesion external elastic membrane (EEM) area/distal reference EEM area) >1.05, the stent was expanded with a balloon sized to the distal reference EEM diameter. In the Angio group, the stent was expanded by visual estimation. In both groups, IVUS was performed after postdilation. Minimum stent area (MSA) and stent volume index were significantly larger in the IVUS versus Angio group (7.1 ± 1.9 vs. 5.9 ± 1.5 mm2 , and 8.7 ± 2.1 vs. 7.5 ± 1.8 mm3 /mm, respectively; p < .01). The percentages of OSE, defined as an MSA ≥5.4 mm2 , MSA ≥90% of distal reference lumen area (DRLA), or MSA > DRLA, were significantly higher in the IVUS versus Angio group (80 vs. 56%, 78 vs. 54%, and 71 vs. 38%, respectively; p < .01). Stent underexpansion, malapposition, and residual reference segment stenosis were significantly higher in the Angio versus IVUS group (44 vs. 12%, 16 vs. 4%, and 12 vs. 0%, respectively; p < .05). In the IVUS group, owing to positive remodeling, there was no incidence of dissection or perforation. This new strategy of IVUS-guided stenting in patients with positive lesion remodeling, compared with angiography, significantly increased stent expansion and decreased stent underexpansion, malapposition, and residual reference segment stenosis with no complications.

Increased glycated albumin and decreased esRAGE levels in serum are related to negative coronary artery remodeling in patients with type 2 diabetes: an Intravascular ultrasound study

BackgroundNegative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients.MethodsSerum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI < 0.95 and intermediate or positive remodeling as an RI ≥ 0.95.ResultsMean plaque burden at the lesion site was 70.96 ± 9.98%, and RI was 0.96 ± 0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r = 0.236, P = 0.005) and was inversely related to serum GA level (r = − 0.240, P = 0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r = − 0.206, P = 0.014) and total cholesterol levels (r = − 0.183, P = 0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012–0.564, P = 0.021), GA (OR 1.093; 95% CI 1.013–1.179, P = 0.018) and LDL-C (OR 1.479; 95% CI 1.072–2.835, P = 0.023) as independent predictors for negative remodeling.ConclusionsIn diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.

Positive Vascular Remodeling in Culprit Coronary Lesion is Associated With Plaque Composition: An Intravascular Ultrasound-Virtual Histology Study.

Background and ObjectivesThe relationship between the positive remodeling (PR) of a coronary artery and plaque composition has been studied only in a relatively small number of study population or non-culprit lesion. We evaluated the association between coronary plaque composition and coronary artery remodeling in a relatively large number of culprit lesions.Subjects and MethodsThe study population consisted of 325 consecutive patients with coronary artery disease that underwent intravascular ultrasound-virtual histology examination in a culprit lesion. The remodeling index (RI) was calculated as the lesion external elastic membrane (EEM) area divided by the average reference EEM area.ResultsThe lesions with PR (RI>1.05, n=97, mean RI=1.19±0.12) had a higher fibrous volume/lesion length (3.85±2.12 mm3/mm vs. 3.04±1.79 mm3/mm, p=0.003) and necrotic core volume/lesion length (1.26±0.89 mm3/mm vs. 0.90±0.66 mm3/mm, p=0.001) than those with negative remodeling (NR) (RI<0.95, n=132, mean RI=0.82±0.09). At the minimal luminal area site, the lesions with PR had a higher fibrous area (5.81±3.17 mm2 vs. 3.61±2.30 mm2, p<0.001), dense calcified area (0.73±0.69 mm2 vs. 0.46±0.43 mm2, p=0.001), and necrotic core area (1.93±1.33 mm2 vs. 1.06±0.91 mm2, p<0.001) than those with NR. RI showed significant positive correlation with fibrous volume/lesion length (r=0.173, p=0.002), necrotic core volume/lesion length (r=0.188, p=0.001), fibrous area (r=0.347, p<0.001), fibrofatty area (r=0.111, p=0.036), dense calcified area (r=0.239, p<0.001), and necrotic core area (r=0.334, p<0.001). Multivariate analysis showed that the independent factor for PR was the necrotic core volume/lesion length (beta=0.130, 95% confidence interval; 0.002-0.056, p=0.037) over the entire lesion.ConclusionThis study suggests that PR in a culprit lesion is associated with the necrotic core volume in the entire lesion, which is a characteristic of vulnerable plaque.

Through IVUS study of characterised the relationship as stable angina (SA) and unstable angina (UA) patients

PurposeAs medical technology advances, the understanding of coronary heart disease from the previous clinical diagnosis, diagnostic ECG, ECG to diagnosis, then diagnostic coronary angiography (coronary angiography CAG), and then by...

Atherosclerotic reference segments influence assessment of coronary remodeling by intravascular ultrasound in patients with acute coronary syndrome

Objective To investigate the influence of atherosclerotic reference segments on coronary remodeling by intravascular ultrasound(IVUS) in patients with acute coronary syndrome(ACS). Methods One hundred and three consecutively enrolled patients [male 68 cases,female 35 cases,average age (60 ±11) years] with ACS were undergone by coronary artery angiography and IVUS with time selecting operation. The remodeling index(RI) was defined as lesion external elastic membrane cross section aere (EEM CSA) divided by the mean reference EEM CSA at the culprit vessel. Positive remodeling was RI≥ (67 cases), negative remodeling was RI <1(36 cases). The parameters of plaque were analysed between two remodeling groups, as well as compared between distal and proximal references. Results Only one patients do not have plaque at reference sites. In the analysis of 103 lesions and 102 reference sites, there were not significant different in plaque burden,plaque CSA,lumen CSA and lesion EEM CSA between two groups. Distal plaque burden[(39. 76 ±12. 54)% vs (32.38 ± 13.97)%, P <0.001] and plaque CSA [(6.14 ± 3.20)mm2 vs (4. 75 ± 3. 07) mm2, P = 0. 001] were larger than those at proximal reference. EEM CSA at distal reference was smaller than proximal one[(14. 99 ± 4. 12)mm2 vs (28. 37 ± 4. 48)mm2 , P <0. 001]. Plaque burden, plaque CSA and lumen CSA persented positive corelation between distal and proximal reference sites. Conclusions The reference segments lay a severe diffuse atherosclerosis in the group of ACS, which may influence assessment of coronary remodeling. Coronary remodeling as a process, a accurate evaluation could be result from the combination of static and serial approach by IVUS. Key words: Endosonography; Coronary disease; Ventricular remodeling; Acute coronary syndrome

Intravascular ultrasound assessment of remodelling and reference segment plaque burden in type-2 diabetic patients

Intravascular ultrasound (IVUS) assesses arterial remodelling by comparing the lesion external elastic membrane (EEM) with the reference segments; however, reference segments are rarely disease-free. The aim was to assess lesion and reference segment remodelling and plaque burden in patients with type-2 diabetes mellitus. We used pre-intervention IVUS to study 62 de novo lesions in 43 patients with type-2 diabetes mellitus. The lesion site was the image slice with the smallest lumen cross-sectional area (CSA). The proximal and distal reference segments were the most normal-looking segments within 5 mm proximal and distal to the lesion. Plaque burden was measured as plaque CSA/EEM CSA. The remodelling index was defined as lesion EEM CSA/mean reference EEM CSA. Reference segment plaque burden measured 0.54 +/- 0.09. The majority of lesions (83.9%) had negative remodelling (lesion EEM < reference). Similarly, the slope of the regression line relating EEM to plaque CSA within the lesion was less than the reference substantiating negative remodelling. The reference segment plaque burden correlated inversely with the difference between IVUS lumen and quantitative coronary angiographic artery size [slope = -0.12 (95% CI -0.17 to -0.07); P < 0.001] in all patients with type-2 diabetes mellitus. Lesions in type-2 diabetic patients are different from previous reports in non-diabetics. Lesions in type-2 diabetics are characterized by a large reference segment plaque burden and negative lesion site remodelling. These IVUS findings may explain the angiographic appearance of small arteries in diabetic patients.

Effect of Simvastatin on Coronary Lesion Site Remodeling: A Serial Intravascular Ultrasound Study

Background: Direct evidence of coronary artery remodeling can be derived only from serial changes in the external elastic membrane (EEM) and plaque area. The aim of the study was to assess the effect of simvastatin on coronary remodeling in serial intravascular ultrasound (IVUS) studies. Methods: In 39 male patients ECG-triggered transducer pullback IVUS was performed at baseline, after 3 months on a lipid-lowering diet (control period), and after another 12 months of simvastatin 40 mg/day. The lesion site was the image slice with maximum plaque burden at 3 months. Results: Absolute changes in the EEM area correlated significantly with changes in plaque area during the control period [B = 0.966, r = 0.792 (95% CI 0.71–1.22); p < 0.001] and during simvastatin treatment [B = 0.945, r = 0.822 (95% CI 0.73–1.16); p < 0.001], but there was no significant difference in the slope (ΔEEM/Δplaque) between the two time intervals. After 12 months of simvastatin, there was a significant reduction in the lesion EEM area of 4.6% (p = 0.006) and in the lesion plaque area of 5.9% (p < 0.001), but there was no change in reference measurements. As a result, the remodeling index was reduced by simvastatin from 1.01 ± 0.12 to 0.95 ± 0.09 (p < 0.001). Conclusion: Simvastatin decreases the remodeling index by reducing lesion, but not reference plaque and EEM area. However, simvastatin does not affect direct evidence of remodeling (ΔEEM/Δplaque) obtained using serial IVUS studies.

Static and serial assessments of coronary arterial remodeling are discordant: An intravascular ultrasound analysis from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial

Arterial remodeling is a major determinant of the clinical manifestations of coronary artery disease. Assessment of arterial remodeling with intravascular ultrasound (IVUS) used to rely on comparing the external elastic membrane (EEM) areas of lesion and reference sites at a single time point (static assessment). Recently, performance of serial IVUS provided the opportunity for direct assessment of remodeling. Our aim was to study the concordance of the static and serial methods. We identified 210 focal coronary lesions on the baseline IVUS interrogations of the REVERSAL trial. A follow-up IVUS was performed at 18 months. Static assessment was performed by calculating the remodeling index (RI) (lesion EEM area / reference EEM area) and serial assessment by comparing the changes in atheroma and EEM areas at follow-up. Using the serial method, there was a 1.24 mm2 increase in EEM area for every 1 mm2 increase in atheroma area at the lesion site, which was indicative of expansive (overcompensatory) remodeling. By using the static method, the RI was paradoxically lower at follow-up (1.062 +/- 0.15 at baseline vs 1.027 +/- 0.14 at follow-up, P < .001), indicating a trend toward constrictive remodeling. The reason for decreased RI at follow-up was the relatively larger expansion of the EEM areas at the reference sites. Static and serial assessments of arterial remodeling are discordant. This is due to concomitant remodeling of the reference sites used in the static assessment. Intravascular ultrasound performed at a single point in time does not reflect the dynamic remodeling response.

Intravascular ultrasound assessment of fibrous cap remnants after coronary plaque rupture

Although intravascular ultrasound (IVUS) can detect plaque rupture, the fibrous cap remnant has not previously been studied in detail. The aim of the present study is to assess the fibrous cap remnants by IVUS in ruptured plaques. In 53 patients, a ruptured plaque with a fibrous cap remnant was studied by IVUS. In 36 (68%) patients, the rupture of the fibrous cap appeared to have occurred at the shoulder. The absolute length of the fibrous cap remnant was significantly longer in the center rupture site compared with the shoulder rupture site (1.37 +/- 0.56 vs 0.84 +/- 0.34 mm, P = .001); however, the estimated length of the original fibrous cap did not differ between the 2 rupture site groups (2.28 +/- 0.66 vs 2.11 +/- 0.69, P = not significant). In none of the patients did the remnants of the fibrous cap cover the entire mouth of the cavity. The estimated absolute length of the missing part of the fibrous cap correlated significantly with the cavity area (r = 0.517, P < .001), the lesion external elastic membrane area (r = 0.330, P = .016), the lumen area (r = 0.289, P = .036), the maximum plaque thickness (r = 0.364, P = .007), and the length of the estimated original fibrous cap (r = 0.709, P < .001). In general, the postrupture fibrous cap does not cover the entire mouth of the ruptured plaque cavity in its postrupture state. Potential explanations include the following: (1) part of the fibrous cap may be too thin to be visualized with IVUS, (2) part of it may have embolized, or (3) the prerupture fibrous cap may have been stretched and/or there were postrupture changes in lesion geometry.

Intravascular Ultrasound Profile Analysis of Ruptured Coronary Plaques

Angiographic studies have shown that lesions preceding nonfatal acute events are usually not hemodynamically significant. This has led to the concept that plaque ruptures occur at minimal disease sites. We used intravascular ultrasound to create a prerupture "profile" of unstable (vulnerable) plaques. We analyzed 112 ruptured plaques detected by intravascular ultrasound. Reference and lesion external elastic membrane (EEM) and lumen areas were measured to calculate prerupture estimates of plaque area, plaque burden (plaque/EEM area), eccentricity, area stenosis, and remodeling. The narrowest coefficients of variance were for lesion EEM area, maximum plaque thickness, and plaque burden, reference lumen area, and remodeling index (coefficients of variance 0.29, 0.25, 0.12, 0.29, and 0.18, respectively); conversely, there was great variability in measurements of calcification and lumen compromise (minimum lumen area and area stenosis). When using the 5 variables with the narrowest coefficient of variance, we found that 67% of ruptured plaques fit all of following 10th or 90th percentile parameters (> 14.3 mm2 lesion EEM area, > 8.1 mm2 reference lumen area, > 1.6 mm maximum lesion plaque thickness, > 0.63 lesion plaque burden, and > 0.87 remodeling index). Further, 89% of ruptured plaques fit 4 of 5 parameters and 96% fit 3 of 5 parameters. In conclusion, plaque ruptures do not occur at minimal disease sites. Rather, vulnerable (rupture-prone) plaques predictably have significant plaque accumulation and remodeling and occur in larger arteries. It is only the degree of lumen compromise that is variable and often insignificant.

Determinants of Arterial Wall Remodeling During Lipid-Lowering Therapy

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. 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. Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

The Impact of Coronary Artery Disease Risk Factors on Intravascular Ultrasound‐Derived Morphologic Indices of Human Coronaries

The relationship of intravascular ultrasound (IVUS)-derived measurements of atherosclerotic plaque to various coronary artery disease (CAD) risk factors is not well known. The purpose of this study was to examine the relationship of percent coronary luminal stenosis by IVUS to other IVUS measures of CAD, as well as the relationship of common IVUS measures of CAD to traditional CAD risk factors. We hypothesized that one or more IVUS measures of CAD might relate more strongly to CAD risk factors than does percent luminal coronary stenosis. The records of 897 consecutive patients (57% men, mean age 62 years) who underwent IVUS investigation of their coronary arteries from 1996 through 2001 were retrospectively reviewed. IVUS was performed using a 20-MHz probe (Jomed, Rancho Cordoba, CA) and a manual pull-back technique to image the coronary arteries. Coronary artery remodeling ratio-i.e., the ratio of coronary lesion external elastic membrane cross-sectional area (EEM CSA) to proximal reference artery EEM CSA; plaque burden-i.e., plaque plus media CSA divided by EEM CSA; calcium arc; and percent stenosis of luminal cross-sectional area were measured by a single reader. Percent area stenosis, the most commonly used IVUS parameter, did not correlate with the other three IVUS-derived parameters, nor was it related to any of the CAD risk factors considered. In contrast, remodeling ratio was directly correlated with plaque burden (r=0.22, P<0.001), but inversely related to calcium arc (r=-0.13, P=0.01). IVUS plaque burden was significantly correlated with male gender (P<0.0001) and diabetes mellitus (DM) (P=0.003). In multivariate analyses including age, gender, and CAD risk factors, plaque burden was significantly associated with age, male gender, and DM, but not with chronic renal failure, hypertension, or hypercholesterolemia. The multivariate model also revealed that the calcium arc was significantly associated with male gender and age. These IVUS findings provide anatomic documentation that the traditional CAD risk factors relate more strongly to plaque burden than to percent coronary arterial luminal narrowing.

Remodeling Index Compared to Actual Vascular Remodeling in Atherosclerotic Left Main Coronary Arteries as Assessed With Long-Term (≥12 Months) Serial Intravascular Ultrasound

We present the remodeling index (RI) versus serial intravascular ultrasound (IVUS) data. The RI, derived by comparing lesion external elastic membrane (EEM) cross-sectional area versus the reference at one time point, is used in various IVUS studies as a substitute of true remodeling (change in EEM over time), assuming that it represents true remodeling. We studied 46 non-stenotic left main arteries using serial IVUS (follow-up 18 +/- 8 months). Plaques were divided into subgroups according to the follow-up RI: follow-up RI >1 (n = 27) versus follow-up RI < or =1 (n = 19). Lesions with a follow-up RI >1 had an increase in lumen despite an increase in plaque because of an increase in EEM. Conversely, lesions with a follow-up RI < or =1 had a reduction in lumen as a result of both a plaque increase and EEM decrease. Overall, the follow-up RI correlated directly with changes in lesion site EEM (baseline-to-follow-up). Although there was no correlation between the follow-up RI and changes in reference EEM area, changes in reference EEM area did correlate directly with changes in lesion EEM area. In nearly 90% of lesions with a follow-up RI >1, there was a previously documented increase in EEM area. Using multivariate linear regression analysis, the follow-up RI was dependent on the baseline RI, the increase in lesion EEM area, and the decrease in reference EEM area. The follow-up RI was not dependent on changes in lesion plaque area. The vast majority of left main lesions with a remodeling index >1 had evidence of a previous increase in lesion-site EEM area.

Mo-S6:4 The place for vascular imaging data in the evidence package for new drugs for atherosclerosis: Regulatory principles

We present the remodeling index (RI) versus serial intravascular ultrasound (IVUS) data.The RI, derived by comparing lesion external elastic membrane (EEM) cross-sectional area versus the reference at one time point, is used in various IVUS studies as a substitute of true remodeling (change in EEM over time), assuming that it represents true remodeling.We studied 46 non-stenotic left main arteries using serial IVUS (follow-up 18 ± 8 months). Plaques were divided into subgroups according to the follow-up RI: follow-up RI >1 (n = 27) versus follow-up RI ≤1 (n = 19).Lesions with a follow-up RI >1 had an increase in lumen despite an increase in plaque because of an increase in EEM. Conversely, lesions with a follow-up RI ≤1 had a reduction in lumen as a result of both a plaque increase and EEM decrease. Overall, the follow-up RI correlated directly with changes in lesionsite EEM (baseline-to-follow-up). Although there was no correlation between the follow-up RI and changes in referenceEEM area, changes in reference EEM area did correlate directly with changes in lesion EEM area. In nearly 90% of lesions with a follow-up RI >1, there was a previously documented increase in EEM area. Using multivariate linear regression analysis, the follow-up RI was dependent on the baseline RI, the increase in lesion EEM area, and the decrease in reference EEM area. The follow-up RI was not dependent on changes in lesion plaque area.The vast majority of left main lesions with a remodeling index >1 had evidence of a previous increase in lesion-site EEM area.

Association of Plaque Characterization by Intravascular Ultrasound Virtual Histology and Arterial Remodeling

Positive remodeling is more often observed in lesions of patients who have acute coronary syndromes or vulnerable (rupture-prone) plaques. However, there are few data that correlate plaque morphology, composition, and arterial remodeling in vivo. We evaluated coronary plaque characterization of lesions with positive remodeling using intravascular ultrasound (IVUS) radiofrequency data analysis. Seventy-seven nonbifurcation native coronary lesions (in 50 patients) were imaged in vivo using 30-MHz IVUS transducers. Lesions were classified into 4 plaque types, fibrous, fibrofatty, dense calcium, and necrotic core, by using processing of the radiofrequency signal validated in vitro. The remodeling index was calculated as the lesion external elastic membrane area divided by the proximal reference external elastic membrane area. Lesions were divided into 2 groups: positive remodeling (remodeling index>1.0, 26 lesions) and intermediate/negative remodeling (remodeling index<or=1.0, 51 lesions). Total plaque volume and the volume of each plaque type were averaged over the length of the lesion. Reference segment plaque compositions were similar. Mean lesion fibrofatty plaque area was significantly larger in lesions with positive remodeling than in lesions with intermediate/negative remodeling (1.2+/-0.7 vs 0.8+/-0.4 mm2, p=0.001; 26.3+/-6.6% vs 19.8+/-5.7%, p<0.001, of total plaque volume). The same results were obtained at the minimum lumen site and in the subgroup of patients who had acute coronary syndromes. Further, there was a linear relation between remodeling index and fibrofatty plaque area (r=0.26, p=0.02). In conclusion, in vivo IVUS radiofrequency data analysis demonstrates that positive remodeling occurs in lesions with more fibrofatty plaque.

Coronary arterial remodeling in differing clinical presentations of unstable angina pectoris--an intravascular ultrasound study.

Coronary arterial remodeling influences the clinical presentation of ischemic heart disease; however, there is little information on the relationship between coronary arterial remodeling and the type of angina pectoris that patients manifest. The study was undertaken to determine the difference of coronary arterial remodeling in patients with different types of angina pectoris. We analyzed 100 patients with ischemic heart disease using intravascular ultrasound (IVUS). Intracoronary IVUS images of proximal reference (PR), distal reference (DR), and target lesion were recorded, and intraluminal area (LA) and external elastic membrane (EEM) were measured. We defined a remodeling index as 100 x (lesion EEM - [PR-EEM + DR-EEM]/2) / ([PR-EEM + DR-EEM]/2). Cases were classified into three groups according to the clinical history (Group 1a: de novo unstable angina pectoris, Group 1b: accelerating unstable angina pectoris, and Group 2; stable angina pectoris). The remodeling index in Group 1a was significantly larger than that in Groups 1b and 2 (18.6 +/- 28.5 vs. 5.3 +/- 27.1 and 18.6 +/- 28.5 vs. -2.7 +/- 17.6, p = 0.0347 and p = 0.0005, respectively), but there was no statistical difference in remodeling index between Groups 1b and 2. Our results indicate that positive coronary arterial remodeling is more prevalent in patients with new onset of angina pectoris. The specific type of coronary arterial remodeling may affect the clinical presentation of patients with coronary artery disease.

Correlation of coronary arterial remodeling determined by intravascular ultrasound with angiographic diameter reduction of 20% to 60%

Negative remodeling is commonly observed in stenotic coronary lesions. It is unknown whether negative remodeling is an early or late event. This study was designed to elucidate when negative remodeling occurs in the development of coronary stenosis. Remodeling was assessed by preintervention intravascular ultrasound in 104 native coronary lesions with intermediate stenosis (20% to 60% of diameter stenosis measured by quantitative coronary angiography). Positive remodeling was defined as lesion external elastic membrane (EEM) cross-sectional area (CSA) greater than the proximal reference, intermediate remodeling as lesion EEM CSA between those of the proximal and distal references, and negative remodeling as lesion EEM CSA less than the distal reference. Positive, intermediate, and negative remodeling were observed in 18%, 32%, and 50%, respectively, of lesions with intermediate stenosis. Lesions with negative and intermediate remodeling had more hard plaque compared with those with positive remodeling (79% vs 70% vs 42%, p = 0.02). Calcium was more frequent in lesions with negative and intermediate remodeling than in those with positive remodeling (52% vs 55% vs 16%, p = 0.01). Lesions with negative remodeling had smaller EEM CSA (11.5 ± 5.2 vs. 13.7 ± 3.4 vs 14.5 ± 5.6 mm 2, p = 0.03) and less plaque (7.9 ± 4.6 vs 10.8 ± 3.4 vs 10.8 ± 4.9 mm 2, p = 0.004) compared with positive and intermediate remodeling lesions, although lumen CSA (3.7 ± 1.7 vs 2.8 ± 0.8 vs 3.6 ± 1.3 mm 2, p = 0.1) and area stenosis (57 ± 15% vs 59 ± 14% vs 56 ± 10%, p = 0.7) were similar. Negative remodeling is frequently observed in lesions with intermediate stenosis. This suggests that negative remodeling occurs early in lesion formation.

Usefulness of preprocedural coronary lesion morphology as assessed by intravasuclar ultrasound in predicting Thrombolysis In Myocardial Infarction frame count after percutaneous coronary intervention in patients with Q-wave acute myocardial infarction

T remains some concern regarding coronary blood flow deterioration in patients after percutaneous coronary intervention (PCI). The corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC) is a quantitative index of coronary blood flow, it reflects microcirculatory damage, and it predicts clinical and functional outcomes after acute infarct intervention.1–3 Intravascular ultrasound (IVUS) assesses lesion morphologies in a way not possible using other techniques. We hypothesized that IVUS would identify morphologic features predictive of the final post-PCI cTFC in patients who had an acute infarction. • • • From 1998 to 2001, we studied infarct related arteries in 43 consecutive patients with IVUS-imaged ST-segment elevation acute myocardial infarction who met the following criteria: (1) native coronary arteries; (2) 72 hours from onset of symptoms to IVUS and intervention; (3) optimum assessment by IVUS and angiography; (4) no angiographic distal embolization or TIMI grade 0 or 1 flow at the end of procedure; and (5) no significant residual stenosis, inflow or outflow disease, or evidence of coronary perforation or flow-limiting dissection by IVUS or angiography. The study included 28 men and 15 women (62 14 years of age). Fifteen patients had received intravenous thrombolysis. Stenosis location was in the left anterior descending coronary artery in 15 patients, left circumflex artery in 8, and right coronary artery in 20. Five patients were treated with balloon alone and 38 with stenting. One patient was treated with thrombectomy before stenting. Nine stents were inserted without predilation and 28 after balloon predilation. Glycoprotein IIb/IIIa inhibitors were used in 8 patients during angioplasty. Angiograms were reviewed blinded to the IVUS results. Quantitative coronary angiography was performed using the CAAS II system (Pie Medical, Maastricht, The Netherlands) on images after intracoronary nitroglycerin in single planes that identified the greatest stenosis severity. Films were recorded at 30 frames/s. The frame count was measured with a frame-counting cine viewer. cTFC was obtained using the technique described by Gibson et al1,2 IVUS was performed with a commercially available system (Boston Scientific Corp./SciMed, Maple Grove, Minnesota) after the intracoronary administration of 100 to 200 g of nitroglycerin. The IVUS catheter was advanced approximately 10-mm distally to the lesion and withdrawn automatically (0.5 mm/s) to the aorto-ostial junction. Studies were recorded on 1/2-in high-resolution s-VHS tapes for off-line analysis. Quantitative analysis was performed using computerized planimetry (TapeMeasure; Indec Systems, Capola, California). Measurements included proximal and distal reference, lesion external elastic membrane (EEM), lumen, plaque and media (EEM minus lumen) cross-sectional areas (mm) and plaque burden (plaque and media divided by EEM). Remodeling index was lesion EMM divided by mean reference EEM. Qualitative assessment was performed according to 2 previously published consensus documents.4,5 When it appeared to be present, thrombus was classified as (1) a low-echoic smooth mass with a distinct interface with the underlying plaque, (2) attached to the vessel wall, or (3) mobile. Statistical analysis was performed using StatView 5.0 (SAS Institute, Cary, North Carolina). Continuous variables are expressed as mean 1SD; categoric variables are expressed as frequencies. Variables were compared using Student’s t test, categoric analysis of variance, and correlation coefficients. Multivariate linear regression analysis was used to assess predictors of cTFC. A p value 0.05 was considered significant. Angiographic findings are listed in Table 1. Heart rate was 80 15 beats/min, systolic blood pressure was 118 19 mm Hg, and diastolic blood pressure was 70 14 mm Hg. Preprocedural IVUS findings are listed in Table 2. Stenosis length was 17 9 mm. There was no difference in stenosis length (p 0.2), plaque media area (p 0.3), and the presence of thrombus (p 0.5) between patients treated with and without preinterventional thrombolysis. Final cTFC correlated with preinterventional stenosis EEM area (r 0.45, p 0.0022), plaque From the Cardiovascular Research Institute, Washington Hospital Center, Washington, DC; and the Cardiovascular Research Foundation, New York, New York. Dr. Weissman’s address is: Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. E-mail: Neil.J.Weissman@medstar.net. Manuscript received November 1, 2002; revised manuscript received and accepted December 3, 2002.