Predictors and outcomes of stent thrombosis: an intravascular ultrasound registry.

AIMS: To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance. METHODS AND RESULTS: A total of 53 patients were enrolled (mean age 61+/-9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1.6+/-0.8 stents/artery with 87% undergoing high-pressure dilatation (> or =14 atmospheres). The minimum stent area was 7.7+/-2.8 mm(2)with a mean stent expansion of 81.5+/-21.9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30.0, P<0.001). Stent thrombosis occurred at 132+/-125 h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%. CONCLUSION: On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.

Impact of pre-interventional arterial remodeling on subsequent vessel behavior after balloon angioplasty: a serial intravascular ultrasound study.

OBJECTIVES: The purpose of this study was to assess the impact of pre-intervention arterial remodeling on subsequent vessel behavior following balloon angioplasty. BACKGROUND: Positive arterial remodeling before intervention has been shown to have a negative impact on the clinical outcome after nonstented coronary interventional procedures. However, the mechanism of interventions in coronary vessel geometry over time is less well characterized. METHODS: Serial (pre-, post- and follow-up) intravascular ultrasound analysis was performed in 46 native coronary lesions. Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index was defined as VA at the target lesion site divided by that of average references. RESULTS: Pre-interventional PR and IR/NR were present in 21 (46%) and 25 (54%) of 46 patients, respectively. At follow-up, the change in plaque area was similar between the two groups (1.3 +/- 2.1 vs. 1.2 +/- 2.1 mm(2), p = 0.840). Lesions with PR showed a significantly smaller change in VA than those with IR/NR (-0.2 +/- 2.5 vs. 1.4 +/- 2.3 mm(2), p = 0.03). As a result, late lumen loss was significantly larger in lesions whose pre-intervention configuration exhibited PR (-1.5 +/- 1.8 vs. 0.2 +/- 1.6 mm(2), p = 0.002). CONCLUSIONS: Lesions with PR appear to have less capacity to compensate for further plaque growth after balloon angioplasty and thus show a proportional increase in late lumen loss. This may in part explain the less favorable clinical outcomes of positively remodeled lesions.

Efficacy of postdeployment balloon dilatation for current generation stents as assessed by intravascular ultrasound.

Adjunctive balloon dilatation strategy has been shown to improve optimal stent deployment. As improvements in current stent designs evolve, less adjunctive balloon dilatation may be needed. However, few data currently exist to support this practice. We evaluated 88 native coronary lesions treated with single stent implantation (Nir, Tristar or S670). Serial intravascular ultrasound was performed after successful stent deployment and again after adjunctive balloon dilatation. To investigate further the precise expansion characteristics of the stents, serial volumetric intravascular ultrasound analyses were performed in 40 patients with automated pullback. After adjunctive balloon dilatation, minimal stent area increased significantly, from 6.4 +/- 2.1 to 7.4 +/- 2.2 mm(2) (p <0.001). Volumetric analysis showed a corresponding increase in stent volume index (6.6 +/- 1.8 to 7.5 +/- 2.0 mm(3)/mm, p <0.001). In the analysis of cross sections at 0.5-mm axial intervals, the percentage of cross sections, where stent area was > or =80% of the average reference lumen area, increased from 51% to 78% (p <0.001). Similarly, the percentage of cross sections, where stent area was > or =90% of the average reference lumen area, increased from 29% to 56% (p <0.001) with postdilatation. Postdeployment high- pressure balloon dilatation improved minimal stent area and volumetric expansion throughout the stented segment.

Fractional flow reserve compared with intravascular ultrasound guidance for optimizing stent deployment.

BACKGROUND: Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria. METHODS AND RESULTS: Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group. CONCLUSIONS: A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

Coronary artery distensibility and compensatory vessel enlargement--a novel parameter influencing vascular remodeling?

Vascular remodeling implies the concept of compensatory vessel enlargement to preserve luminal dimensions during atheromatous plaque development. However, negative remodeling, i.e. vessel shrinkage in response to plaque accumulation has also been described. So far, the factors influencing positive or negative remodeling are uncertain. We hypothesized that vascular distensibility, a measure of vessel compliance, is related to compensatory enlargement. In 58 patients undergoing intravascular ultrasound interrogation of a de novo lesion prior to coronary intervention, the cross-sectional vessel area (VA), lumen area (LA) and plaque area (PA = VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Positive remodeling was defined to be present when the VA at the lesion was > 1.05 times larger than that at the proximal reference (group A), negative remodeling when the VA at the lesion was < 0.95 of the reference site (group C) and in-between was considered to be intermediate (group B). Vessel compliance was measured by calculating vascular distensibility. Results showed a similar LA at the lesion site in all groups (4.18+/-2.18 vs. 4.36+/-1.19 vs. 3.74+/-1.81 mm2, NS) while VA and PA were significantly larger in group A (17.19+/-5.08 vs. 14.22+/-3.66 and 12.45+/-4.82 mm2, p = 0.005 and 13+/-4.55 vs. 9.95+/-3.58 and 8.7+/-3.83, p = 0.003, respectively). Vascular distensibility at the proximal reference segment was significantly greater in group A (3.55+/-2.67 vs. 1.25+/-1.03 and 0.85+/-0.73 mmHg(-1), p < 0.001) with a positive correlation between remodeling and distensibility (R = 0.52, p < 0.001). In a multiple regression model including clinical and lesional factors, distensibility was the only predictor of remodeling. In conclusion, these results suggest that compensatory vessel enlargement occurs to a greater degree in patients with increased coronary artery distensibility, which appears to be a predictor for positive remodeling.

Novel drug-delivery stent: intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system.

BACKGROUND: The aim of this study was to use serial intravascular ultrasound (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a taxane analogue) delivery on neointimal tissue growth within the stent and on vessel dimensions at the adjacent reference segments. METHODS AND RESULTS: Serial IVUS analyses (immediately after intervention and at follow-up at 8.3 months) were performed in 15 native coronary lesions treated with the QuaDS-QP2 stent. IVUS measurements were performed at 8 cross-sections in each target segment (4 cross-sections within the stent and 2 cross-sections in each reference segment). At baseline, no significant plaque protrusion or thrombus was detected in the target segment. Mild incomplete stent apposition and edge dissection were observed in one and two cases, respectively. Percent expansion of the stent (minimum stent area/average reference lumen area) was 96.0+/-21.7%. At follow-up, mean neointimal area within the stent was 1.2+/-1.3 mm(2), and mean cross-sectional narrowing (neointimal area/stent area) was 13.6+/-14.9%. At the vessel segments immediately adjacent to the stent, a significant increase in plaque area (1.9+/-2.6 mm(2), P=0.001) was observed, but vessel area remained unchanged. However, no patients showed clinically significant in-stent or edge restenosis (diameter stenosis >/=50%) during the follow-up period. CONCLUSIONS: The first human experience with the new drug-delivery stent showed a minimal amount of neointimal proliferation in the stented segment. Late lumen loss at the reference sites adjacent to the stent was acceptable and predominantly due to plaque proliferation.

Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study.

BACKGROUND: Vessel remodeling is an important mechanism of late lumen loss after nonstent coronary interventions. However, its impact on in-stent restenosis has not been systematically investigated. METHODS AND RESULTS: Serial volumetric intravascular ultrasound analyses (poststent and follow-up) were performed in 55 lesions treated with a balloon-expandable stent (ACS MultiLink) using standard stent deployment techniques. The vessel volume (VV), lumen volume (LV), and volume bordered by the stent (SV) were measured using Simpson's method. The volume of plaque and neointima outside the stent (peri-stent volume, PSV) and volume of neointima within the stent (intrastent volume) were also measured. The change of each parameter during the follow-up period (follow-up minus poststent) was calculated and then divided by SV to normalize these values (designated as percent change [%]). As expected, %PSV directly correlated with %VV (P<0.0001, r=0.935), with no significant SV. A highly significant inverse correlation was seen between %PSV and the percent change of intrastent volume (P<0.0001, r=0.517). Consequently, %LV significantly correlated with peri-stent remodeling, as measured by %VV (P<0.0001, r=0.602). CONCLUSION: Positive remodeling of the vessel exterior to a coronary stent occurs to a variable degree after stent implantation. There is a distinct trade-off between positive remodeling and in-stent hyperplasia: in segments in which the degree of peri-stent remodeling is less, intrastent neointimal proliferation is greater and accompanied by more significant late lumen loss.

Intravascular sonotherapy decreases neointimal hyperplasia after stent implantation in swine.

BACKGROUND: Intimal hyperplasia and subsequent in-stent restenosis remain a major limitation after stent implantation. In vitro cell culture studies show that low-frequency, noncavitational ultrasound energy may impact smooth muscle cell proliferation. Accordingly, we assessed the efficacy of intravascular sonotherapy treatment on intimal hyperplasia in a swine stent model. METHODS AND RESULTS: After balloon injury, biliary stents (Johnson & Johnson) were implanted in the femoral arteries of 14 swine. A total of 48 stented sites were randomized to sonotherapy or sham treatment using a custom-built, 8-French catheter intravascular sonotherapy system (URX, PharmaSonics Inc). After stent deployment, ultrasound energy (700 KHz) was applied to the treatment group for up to 5 minutes. Smooth muscle cell proliferation was assessed using bromodeoxyuridine histology preparation (BrdU) at 7 days in 28 stented sites. At 28 days, the neointimal thickness and the ratio of neointimal/stent area (percent stenosis) was calculated by histomorphometric quantification in 20 stented sites. At 7 days, percent of BrdU staining was significantly reduced in the sonotherapy group compared with the sham group (24.1+/-7.0% versus 31.2+/-3.0%, P<0.05). At 28 days, percent stenosis was significantly less in the sonotherapy group than in the sham group (36+/-24% versus 44+/-27%, P<0.05), and the mean neointimal thickness in the sonotherapy group was less than in the sham group (417+/-461 micrometer versus 643+/-869 micrometer, P=0.06). CONCLUSIONS: In this swine peripheral model, intravascular sonotherapy seemed to decelerate cellular proliferation and decrease in-stent hyperplasia. Therefore, intravascular sonotherapy may be an effective form of nonionizing energy to reduce in-stent restenosis.

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.

Preintervention arterial remodeling affects clinical outcome following stenting: an intravascular ultrasound study.

OBJECTIVES: The study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting. BACKGROUND: The impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified. METHODS: Preintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments. RESULTS: Positive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 +/- 1.80 vs. 8.09 +/- 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02). CONCLUSIONS: Lesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation.

Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model.

OBJECTIVE: Motexafin lutetium (Lu-Tex, Antrin Injection) is a photosensitizer that selectively accumulates in atheromatous plaque where it can be activated by far-red light. The localization and retention of intra-arterially administered Lu-Tex and its efficacy following activation by endovascularly delivered light (photoangioplasty) was evaluated. METHODS: Bilateral iliac artery lesions were induced in 17 rabbits by balloon denudation, followed by a high cholesterol diet. Lu-Tex distribution within the atheroma was examined (n=8) following local injection. Fluorescence spectral imaging and chemical extraction techniques were used to measure Lu-Tex levels within the atheroma and adjacent normal tissue. Photoactivation was performed 15 min following Lu-Tex administration (180 J/cm fiber at 200 mW/cm fiber). Two weeks post photoangioplasty, vessels were harvested and hematoxylin and eosin (H&E) and RAM11 (macrophages) staining was performed. RESULTS: Local delivery of Lu-Tex achieved immediate high concentrations within plaque (mean 40x control iliac atheroma). Mean percent plaque area in the treated segments was significantly lower than in the non-treated contralateral lesions (73 vs. 82%, P<0.01). No medial damage was observed. Quantitative analysis using RAM11 positive cells revealed significant reduction of macrophages in treated lesions in both the intima (5 vs. 22%, P<0.01) and in media (8 vs. 23%, P<0.01) compared to untreated contralateral segments. CONCLUSIONS: Local delivery provides high levels of Lu-Tex selectively within atheroma. Photoactivation results in a significant decrease in macrophage and a small decrease in atheroma burden without damage to the normal vessel wall.

Efficacies of sirolimus (rapamycin) and cyclosporine in allograft vascular disease in non-human primates: trough levels of sirolimus correlate with inhibition of progression of arterial intimal thickening.

We investigated the efficacies of sirolimus (rapamycin) and cyclosporine for inhibition of graft vascular disease (GVD) in cynomolgus monkey recipients of aortic allografts. Increases in arterial intimal thickening in the midgraft (six consecutive cross-sections) after transplantation were quantified by serial intravascular ultrasound (IVUS) from day 21 to day 105. These data enabled correlations between changes in intimal indexes [II = (intimal area/vessel area) x 100] and trough levels of sirolimus and cyclosporine to be determined. Eighteen recipients received no immunosuppression for 6 weeks to allow alloimmune injury to occur. On day 45, monkeys were treated daily with sirolimus (n = 6) or cyclosporine (n = 6); six monkeys remained untreated. II increased significantly from day 63 to day 105 in untreated monkeys and monkeys treated with cyclosporine, whereas monkeys treated with sirolimus did not have a significant increase in II (P = 0.008, P = 0.006, P = NS; paired t-test). The change in II from days 63 to 105 was significantly greater in untreated monkeys compared to sirolimus-treated monkeys (P = 0.13; one-way ANOVA, P = 0.012 Tukey's post hoc test); other post hoc pairwise comparisons were not significant. Mean sirolimus and cyclosporine levels +/- SEM were 43 +/- 7 ng/ml and 562 +/- 20 ng/ml, respectively. Sirolimus trough levels, but not cyclosporine levels, correlated inversely with changes in II from day 42 to 105 (r2 = 0.73, P = 0.03). This non-human primate study shows that inhibition of intimal thickening by sirolimus depends on trough levels and provides the rationale for clinical trials of sirolimus for the control of GVD in organ transplant recipients.

Longitudinal plaque redistribution during stent expansion.

The purpose of this study was to clarify the 3-dimensional behavior of plaque during coronary stent expansion. Serial intravascular ultrasound (IVUS) studies, preintervention, and poststenting were evaluated in 32 patients treated with a single-balloon expandable tubular stent. External elastic membrane (EEM), lumen, stent, and plaque + media cross-sectional area were measured at 1-mm intervals through the entire stent as well as proximal and distal reference segments 5 mm from the stent edge. Volumetric calculations were based on Simpson's rule. Overall, the plaque + media volume through the entire lesion did not change during stent expansion (218 +/- 51 vs 217 +/- 47 mm3, p = 0.69). However, EEM and lumen volume increased significantly (EEM volume, 391 +/- 84 vs 448 +/- 87 mm3 [p < 0.0001]; lumen volume, 173 +/- 52 vs 231 +/- 54 mm3 [p < 0.0001]). The change in lumen volume correlated strongly with the change in EEM volume (r = 0.85, p < 0.0001), but poorly with the change in plaque + media volume (r = 0.37, p = 0.03). Plaque + media volume decreased in the midstent zone (59 +/- 14 vs 53 +/- 11 mm3, p = 0.0005), and increased in the distal stent zone (40 +/- 11 vs 44 +/- 9 mm3, p = 0.003), but did not change in either the proximal stent zone or reference segments. The mechanism of stent expansion is a combination of vessel stretch and plaque redistribution, translating disease accumulation from the midstent zone to the distal stent zone.

Selective regional myocardial infiltration by the percutaneous coronary venous route: A novel technique for local drug delivery.

Recent advances in the treatment of heart disease, in particular cardiovascular gene therapy and therapeutic angiogenesis, highlight the need for efficient and practical local delivery methods for the heart. We assessed the feasibility of percutaneous selective coronary venous cannulation and injection as a novel approach to local myocardial drug delivery. In anesthetized swine, the coronary sinus was cannulated percutaneously and a balloon-tipped catheter advanced to the anterior interventricular vein (AIV) or middle cardiac vein (MCV). During balloon occlusion, venous injection of radiographic contrast caused regional infiltration of targeted myocardial regions. Complete AIV occlusion had no impact on LAD flow parameters. Videodensitometric analysis following venous injection showed that radiographic contrast persisted for at least 30 min. Selective regional myocardial infiltration is feasible by this approach, targeting selected myocardial beds, including the apex, anterior wall, septum, and inferoposterior wall. This novel technique has potential application for local myocardial drug or growth factor delivery. Cathet. Cardiovasc. Intervent. 51:358-363, 2000.

Comparison of coronary stent expansion by intravascular ultrasonic imaging in younger versus older patients with diabetes mellitus.

The poor long-term outcome in young diabetic patients receiving stents is not well understood. The purpose of this study was to characterize the pastprocedural results of stent placement in diabetic patients using intravascular ultrasound to identify factors that might be associated with poor clinical outcome. The acute dimensions from intravascular ultrasound studies after stent deployment at 5 sites were measured from 39 coronary segments from patients with diabetes mellitus (DM) and 161 segments from nondiabetic patients (non-DM). Within these 2 groups, segments were subgrouped into young (y) and old (o) in reference to the mean study age of 64 years, forming 4 groups: yDM (n = 20), y non-DM (n = 65), oDM (n = 19), and o non-DM (n = 96). Results are reported as mean +/- 1 SD. Diabetic patients had smaller mean lumen area within the treated segment than o non-DM (8.37+/-2.59 vs. 9.11+/-3.35 mm2, p<0.01). These differences were more pronounced at the distal reference vessel lumen of yDM than y non-DM (7.6+/-2.3 vs. 10.3+/-4.5 mm2, p<0.003), and were associated with greater percent plaque area in the distal reference vessel (43.4+/-13% vs. 34.1+/-11.2%, p<0.003). In young diabetic patients undergoing elective stent placement, underexpansion of the stented segment is common, which may contribute to the relatively poor long-term outcome in these patients. We suggest that when stenting is the procedure of choice in this subgroup of high-risk patients, special attention should be given to optimizing lumen dimensions.

Use of fractional myocardial flow reserve to assess the functional significance of intermediate coronary stenoses.

The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

Sirolimus (rapamycin) halts and reverses progression of allograft vascular disease in non-human primates.

BACKGROUND: Current immunosuppressive protocols fail to prevent chronic rejection often manifested as graft vascular disease (GVD) in solid organ transplant recipients. Several new immunosuppressants including sirolimus, a dual function growth factor antagonist, have been discovered, but studies of drug efficacy have been hampered by the lack of a model of GVD in primates, as a prelude to clinical trials. As described earlier, we have developed a novel non-human primate model of GVD where progression of GVD is quantified by intravascular ultrasound (IVUS). METHODS: Twelve cynomolgus monkeys underwent aortic transplantation from blood group compatible but mixed lymphocyte reaction-mismatched donors. To allow the development of GVD in the allograft, no treatment was administered for the first 6 weeks. Six monkeys were treated orally with sirolimus from day 45 after transplantation to day 105. RESULTS: Progression of GVD measured as change in intimal area from day 42 to 105 was halted in sirolimus-treated monkeys compared to untreated monkeys (P<0.001, general linear model). On day 105, the intimal area +/- SEM was 3.7+/-1.0 and 6.4+/-0.5 mm2, respectively (P<0.05, t test). The magnitude of allograft intimal area on day 105 correlated inversely with sirolimus trough levels (R2=0.67, P<0.05). Regression of the intimal area was seen in four of six sirolimus-treated monkeys, which was significantly different from the untreated monkeys (P<0.05). CONCLUSIONS: Our results in the first non-human primate model of GVD showed that treatment with sirolimus not only halted the progression of preexisting GVD but also was associated with partial regression. Sirolimus trough blood levels were correlated with efficacy. Therefore, sirolimus has the potential to control clinical chronic allograft rejection.

Feasibility of a novel blood noise reduction algorithm to enhance reproducibility of ultra-high-frequency intravascular ultrasound images.

BACKGROUND: Ultra-high-frequency (40- to 50-MHz) intravascular ultrasound (IVUS) improves image quality compared with conventional 20- to 30-MHz IVUS. However, as the frequency of IVUS increases, high-intensity backscatter from blood components may cause visual difficulties in discrimination between the lumen and arterial wall structure. The purpose of this study was to evaluate the effect of a novel blood noise reduction algorithm (BNR) on quantitative coronary ultrasound measurements. METHODS AND RESULTS: IVUS studies using a 40-MHz transducer were performed in 35 patients with coronary artery disease. A total of 620 gray-scale images (310 pairs) were processed with and without the BNR, and lumen cross-sectional area (CSA) was determined by 2 independent observers. With the BNR, the intraobserver and interobserver correlation coefficients for lumen CSA were significantly improved (0.85 to 0.99 and 0.80 to 0.98, respectively). In the 270 images (135 pairs) in which vessel wall measurements were possible, the BNR significantly improved the intraobserver and interobserver correlation coefficients for plaque plus media CSA (0.83 to 0.99 and 0.76 to 0.97, respectively), whereas no influence was observed for external elastic membrane CSA (1.00 to 1.00 and 0.99 to 0.99, respectively). CONCLUSIONS: This study demonstrates the feasibility of this novel algorithm to reduce blood noise, thereby enabling accurate lumen border delineation and providing reproducible measurements of both the lumen and plaque plus media CSAs. Incorporating a digital BNR may serve as an important adjunct to ultra-high-frequency IVUS imaging for improving accurate quantitative evaluation of vessel dimensions.