Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent: intravascular ultrasound results from ENDEAVOR III.

BACKGROUND: The purpose of this study was to investigate the vascular response of zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial intravascular ultrasound (IVUS). METHODS: Data were obtained from the Endeavor Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a randomized study comparing ZES and SES for the treatment of de novo native coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was available in 258 patients (190 ZES, 68 SES). RESULTS: At 8 months, ZES had greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm3/mm vs SES 0.2 +/- 0.1 mm3/mm, P < .01), resulting in smaller lumen volume index (6.0 +/- 2.0 mm3/mm vs 7.0 +/- 2.1 mm3/mm, P < .05). Zotarolimus-eluting stents showed larger IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P < .01) and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P < .01). Zotarolimus-eluting stents had a significantly lower incidence of late-acquired incomplete stent apposition. CONCLUSIONS: Zotarolimus-eluting stent is associated with a significantly greater amount of neointimal hyperplasia compared with SES. This amount of hyperplasia in ZES is distributed throughout the stent at 8-month follow-up.

Neointimal progression and luminal narrowing in sirolimus-eluting stent treatment for bare metal in-stent restenosis: a quantitative intravascular ultrasound analysis.

BACKGROUND: Recurrent restenosis may occur after drug-eluting stent implantation for in-stent restenosis (ISR) of bare metal stents (BMSs), especially in areas involving drug-eluting stent gaps. METHODS: To investigate the details of neointimal progression and luminal narrowing after the treatment of ISR using sirolimus-eluting stents (SESs), serial intravascular ultrasound analysis was performed in 65 patients with ISR at postintervention and at 6-month follow-up. The total stented segment was categorized into 3 compartments: new SES (N), new SES and old BMS overlap (N/O), and old BMS (O). In each of the 190 compartments, serial intravascular ultrasound parameters were analyzed at the cross section of the maximum change in neointimal area (delta neointimal area) from postintervention to follow-up or the minimum lumen area at follow-up if delta neointimal area was 0. Minimum lumen area in each compartment was also investigated serially. RESULTS: At postintervention, lumen area was the smallest in compartment N/O (N 5.8 +/- 1.5, N/O 5.1 +/- 1.3, O 6.0 +/- 1.4 mm2, P = .005). Not only the average of maximum delta neointimal area (N 0.2 +/- 0.4, N/O 0.2 +/- 0.4, O 0.8 +/- 1.0 mm2, P < .0001) but also the frequency of minimum lumen area decreasing from > or = 4.0 mm2 at postintervention to < 4.0 mm2 at follow-up (N 4.0%, N/O 5.1%, O 23.5%, P = .012) was the largest in compartment O. CONCLUSIONS: Neointimal progression and consequent luminal narrowing tend to occur where BMS is uncovered with SES in treatment of ISR, even in the absence of an obvious stenosis at postintervention.

Impact of gender on neointimal hyperplasia following coronary artery stenting.

Whether gender affects long-term outcomes after bare metal stent implantation remains controversial. The aim of this study was to examine the impact of gender on neointimal hyperplasia in a large cohort of patients after stent implantation using 3-dimensional intravascular ultrasound. Lumen and stent areas were manually traced at 0.5-mm intervals throughout the stented segment. Using Simpson's method, lumen, stent, and neointimal (stent - lumen) volumes were calculated and standardized by stent length. Women were older, presented more often with hyperlipidemia or hypertension, and had smaller reference vessel diameter and mean stent area, compared with men. Although neointimal hyperplasia and neointimal thickness in women were similar to that in men, the percentage of neointimal hyperplasia (neointimal area divided by stent area) was higher in women due to the smaller stent area. After adjusting for stent area, the percentage of neointimal hyperplasia did not differ by gender. In conclusion, the results of this study indicate that neointimal hyperplasia after bare metal stent implantation in women is similar to that seen in men. Despite the similarity in outcome, there are several gender-specific differences in baseline characteristics.

Serial intravascular ultrasonic study of outcomes of coronary culprit lesions with plaque rupture following bare metal stent implantation in patients with angina pectoris.

Coronary culprit lesions with plaque rupture (PR) have been treated with different coronary interventions. However, it is unknown whether the presence of PR affects the restenotic process after coronary intervention. One hundred forty-two patients undergoing coronary bare metal stent implantation were enrolled in the present retrospective analysis. Case selection was based on availability of intravascular ultrasound (IVUS) and quantitative coronary angiographic examinations at baseline (before and after intervention) and at follow-up. Serial comparative analyses included qualitative and quantitative features of the culprit lesion and reference segments. PR was defined as an intraplaque cavity in communication with the lumen in the presence of a residual, disrupted cap. Patients were categorized according to the presence/absence of PR. Pre-interventional IVUS detected PR in 54 patients (38%). Baseline patient demographics were similar between the +PR and -PR groups. Quantitative IVUS analysis showed higher rates of positive remodeling and larger vessel and plaque areas in the +PR compared with -PR lesions (p <0.001 for all). At follow-up (7.2 +/- 2.6 months), no statistically significant difference was observed between the 2 groups in quantitative coronary angiographic or IVUS measurements. In conclusion, culprit lesions with PR exhibited larger plaque mass and higher rates of positive remodeling at preintervention IVUS examination. However, when treated with bare metal stents, the absence/presence of preintervention PR was not found to affect the rate or severity of in-stent restenosis in these culprit lesions.

Intravascular ultrasonic analysis of atherosclerotic vessel remodeling and plaque distribution of stenotic left anterior descending coronary arterial bifurcation lesions upstream and downstream of the side branch.

Bifurcation lesions remain a challenging lesion subset, even in the era of drug-eluting stents. The aim of this study was to investigate the longitudinal remodeling pattern and cross-sectional plaque location of bifurcation lesions. Seventy-four preintervention intravascular ultrasound studies of left anterior descending bifurcation lesions were analyzed, in which the lesion was located proximal (type A, n=32) or distal (type B, n=42) to the side branch. Vessel area and plaque area at the lesion (VAlesion and PAlesion) and at the reference site (VAreference and PAreference) were measured. The remodeling ratio was defined as VAlesion/VAreference, and the vessel compensation ratio was defined as (VAlesion-VAreference)/(PAlesion-PAreference). The geometric center of the lumen at the lesion site was identified, and the lesion site was divided into circumferential equal arcs to compare the cross-sectional distribution of percentage plaque area (100x[PAlesion/VAlesion]) between the 2 groups. The remodeling ratio (1.03+/-0.15 vs 0.94+/-0.14, p=0.01) and the vessel compensation ratio (0.0+/-0.36 vs -0.37+/-0.61, p<0.01) were significantly greater in type A than in type B lesions. The circumferential distribution pattern of percentage plaque area was significantly different between the groups (analysis of variance p<0.005), with greater percentage plaque area for the vessel wall opposite from the side branch in type B lesions (46.3+/-18.0% vs 54.6+/-15.4%, type A vs type B lesions, p<0.05). In conclusion, these results suggest that a major side branch may affect longitudinal lesion remodeling as well as the circumferential location of atherosclerotic plaque.

Delivered dose and vascular response after beta-radiation for in-stent restenosis: retrospective dosimetry and volumetric intravascular ultrasound analysis.

BACKGROUND: Observations from previous intracoronary radiation therapy trials noted a considerable discrepancy between the prescribed radiation dose and the dose actually delivered. The aims of this study were to investigate the effect of actual delivered dose on vascular changes and to test the appropriateness of the current dose prescription. METHODS AND RESULTS: Serial volumetric intravascular ultrasound (IVUS) analysis was performed in 30 in-stent restenosis cases treated with a 40-mm (90)Sr/Y source train. The fixed dose was prescribed at 2 mm from the centerline of the source train (18.4 Gy at 2 mm for reference diameter < or =3.35 mm and 23 Gy for diameter > or =3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). D(S90)EEM (the minimum dose absorbed by 90% of the external elastic membrane surface) was calculated as the delivered dose corresponding to each segment, assuming that the radiation catheter occupied the same position in the vessel as the IVUS catheter. Mean D(S90)EEM of 23.5+/-5.82 Gy (range 12.3 to 41.7 Gy) was delivered to these subsegments. Overall, intimal hyperplasia volume remained constant from postintervention to follow-up (2.23+/-1.10 to 2.32+/-1.09 mm3/m; P=NS). Regression analysis revealed there was no correlation between delivered dose intensity and changes in intimal hyperplasia volume. No particular dose-dependent complications were appreciated in this delivered dose range. CONCLUSIONS: The current dose-prescription protocol of (90)Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.

Impact of final stent dimensions on long-term results following sirolimus-eluting stent implantation: serial intravascular ultrasound analysis from the sirius trial.

OBJECTIVES: We assessed the predictive value of minimum stent area (MSA) for long-term patency of sirolimus-eluting stents (SES) implantation compared to bare metal stents (BMS). BACKGROUND: Although MSA is a consistent predictor of in-stent restenosis, its predictive value in BMS is still limited because of biologic variability in the restenosis process. METHODS: From the SIRolImUS (SIRIUS) trial, 122 cases (SES: 72; BMS: 50) with complete serial intravascular ultrasound (IVUS) (baseline and 8-month follow-up) were analyzed. Postprocedure MSA and follow-up minimum lumen area (MLA) were obtained. Based on previous physiologic studies, adequate stent patency at follow-up was defined as MLA >4 mm(2). RESULTS: In both groups, a significant positive correlation was observed between baseline MSA and follow-up MLA (SES: p < 0.0001, BMS: p < 0.0001). However, SES showed higher correlation than BMS (0.8 vs. 0.65) with a higher regression coefficient (0.92 vs. 0.59). The sensitivity and specificity curves identified different optimal thresholds of MSA to predict adequate follow-up MLA: 5 mm(2) for SES and 6.5 mm(2) for BMS. The positive predictive values with these cutoff points were 90% and 56%, respectively. CONCLUSIONS: In this SIRIUS IVUS substudy, SES reduced both biologic variability and restenosis, resulting in increased predictability of long-term stent patency with postprocedure MSA. In addition, SES had a considerably lower optimal MSA threshold compared to BMS.

Predictors of edge stenosis following sirolimus-eluting stent deployment (a quantitative intravascular ultrasound analysis from the SIRIUS trial).

To study the interaction of the sirolimus-eluting stent and vessel margins, we analyzed the intravascular ultrasound parameters in 317 edges of 167 stents having 18 edge stenoses at 8 months of follow-up from the SIRIUS trial. Of the baseline parameters, a larger reference percentage of plaque area and a larger edge stent area/reference minimum lumen area were associated with edge stenosis in the sirolimus-eluting stent cohort compared with the incidence of edge stenosis in the bare metal stent cohort. Thus, full lesion coverage and matching the stented segment properly to the adjacent segment using intravascular ultrasound guidance may improve sirolimus-eluting stent implantation efficacy further.

Mechanism of lumen gain with a novel rotational aspiration atherectomy system for peripheral arterial disease: examination by intravascular ultrasound.

OBJECTIVE: The purpose of this study was to evaluate the mechanism of luminal gain with a novel atheroablation system (Pathway PV) for the treatment of peripheral artery disease using intravascular ultrasound (IVUS). METHODS: The atherectomy system is a rotational atherectomy device, which employs expandable rotating blades with ports that allow flushing and aspiration of the plaque material or thrombus. In this first-in-man clinical study, IVUS analysis was available in 6 patients with lower limb ischemia treated with this device. The treatment results were assessed using IVUS at pre and post atherectomy. Lumen beyond burr size (LBB) was defined as lumen gain divided by the estimated burr area determined by the burr-size. RESULTS: IVUS analysis was available in six patients (superficial femoral artery n=3, popliteal artery n=2, posterior tibial artery n=1). Atheroablation achieved a significant increase in lumen area (LA) (preintervention 3.9+/-0.4, postatheroablation 8.0+/-1.7 mm(2), P<.05), and significant reduction in plaque area (27.5+/-4.0, 23.7+/-3.1 mm(2), P=.001), while there was no change in the vessel area (31.3+/-4.2, 32.1+/-2.8 mm(2), P=.4). LBB was 57.4+/-51.3%. CONCLUSION: This novel rotational aspiration atherectomy device achieved significant luminal gain by debulking in the absence of vessel stretching. The LA was greater than burr-sized lumen expectancy at cross-sections along the treated segments, suggesting a complimentary role of aspiration in luminal gain in atherosclerotic peripheral artery lesions.

A Novel Technique for Endovascular Detection and Removal of Radiographic Contrast during Angiography.

OBJECTIVES: This study aims at in-vitro validation of the principles of endovascular detection of contrast medium and assessing the feasibility of in-vivo detection and removal of contrast during angiography. BACKGROUND: Contrast-induced nephropathy is a growing concern in current percutaneous interventions with increasing lesion complexity and patient comorbidity. To address this clinical problem, a novel method of endovascular detection and automatic removal of contrast has been developed, and is comprised of a catheter-based system with a reflectance-type optical sensor. METHODS: Blood samples were obtained from ovine subjects to characterize the optical response of blood by measuring the reflectance spectrum at varying levels of hematocrit diluted by a contrast agent. The results from the in-vitro test were implemented into an in-vivo system. An aspiration catheter equipped with a fiberoptic sensor was inserted into the coronary sinus (CS) of 5 canines. Contrast was administered through the coronary artery and reflectance signals were recorded at the CS. The removal rate was analyzed through 20 specimen collections. RESULTS: A proportional relationship was found between hematocrit and reflectance intensity in in-vitro test. Upon in-vivo detection of contrast, the sensor signal showed a 79.5 +/- 9.9% (n = 33) drop from the pre-injection baseline. This was highly reproducible and beyond the noise level of baseline, (2.5 +/- 0.9%), enabling automatic activation of the aspiration system. The signal duration was 12.2 +/- 3.7 seconds. The removal rate of contrast was 59.3 +/- 11%. CONCLUSION: The present study validated the principles of endovascular contrast detection and demonstrated the feasibility of an in-vivo, catheter-based removal of contrast using reflectance technology.

Two-year intravascular ultrasound observations in diabetic patients treated with single and double dose sirolimus-eluting stents: results of the double dose diabetes (3D) study.

BACKGROUND: Diabetes has been reported as an independent predictor of restenosis after drug-eluting stent implantation. The purpose of this study was to assess the long-term impact of increased drug dose in sirolimus-eluting stents (SES) on neointimal hyperplasia (NIH) in diabetic patients using volumetric intravascular ultrasound analysis. METHODS: The 3D trial is a multicenter, prospective, randomized, feasibility study of double-dose (280 microg/cm2) or conventional single-dose (140 microg/cm2) SES for the treatment of de novo coronary lesions in diabetic patients. To evaluate long-term efficacy, complete serial volumetric analyses (baseline, 6-month and 2-year follow up) were performed in 39 diabetic patients (17 single-dose, 22 double-dose). Each volume was divided by stent length to acquire volume index, expressed as mm3/mm. Percent neointimal volume was calculated as (neointimal volume/stent volume) x 100 at follow up. RESULTS: Volumetric analysis showed similar results over time between the 2 stent groups (p = NS for all). At 2-year follow up, minimal increases in NIH area and percent NIH were observed in both groups, which translated into a decrease in lumen volume index compared to baseline (p < 0.05 for all). No late-acquired incomplete stent apposition was observed in either group. CONCLUSIONS: The current single dose of sirolimus in SES is effective in inhibiting NIH in diabetic patients up to 2 years. In this patient subset, double-dose SES did not confer additional NIH suppression at 2-year follow up compared to conventional single-dose SES.

Impact of different definitions on the interpretation of coronary remodeling determined by intravascular ultrasound.

The objective of this study was to compare the categorizations and determinants related to remodeling by the three definitions commonly used. Several morphological and intravascular ultrasound (IVUS) studies have demonstrated the fundamental importance of arterial remodeling in atherosclerosis. However, lack of consensus on how to define remodeling has led to conflicting analyses of factors that influence this process. Analysis of pre-interventional IVUS images of 514 lesions in native coronary arteries was performed. Arterial remodeling was defined as outward by definition 1, when [cross-sectional area (CSA) of the external elastic membrane (EEM) at the lesion site (EEM(lesion))]/[EEM CSA either at the proximal (EEM(prox ref)) or distal (EEM(distal ref)) reference site with the least amount of plaque] was > 1.05, intermediate when this ratio was between 0.95 and 1.05, and inward when < 0.95. Remodeling was defined as outward by definition 2 when EEM(lesion) > both EEM(prox ref) and EEM(distal ref), inward when EEM(lesion) < both EEM(prox ref) and EEM(distal ref), and intermediate when EEM(lesion) was intermediate between EEM(prox ref) and EEM(distal ref). By definition 3, vessel remodeling was defined as outward when EEM(lesion) > (EEM(prox ref) + EEM(distal ref))/2 and intermediate/inward when EEM(lesion) < or = (EEM(prox ref) + EEM(distal ref))/2. The frequency of outward remodeling was significantly higher by definitions 1 and 3 than by definition 2, whereas a higher frequency of inward remodeling was observed in definition 1, resulting in significantly different remodeling distributions between the three definitions (P < 0.0001). By multivariate logistic analysis, the only clinical determinants related to outward remodeling was younger age, and only by definition 3. IVUS determinants varied significantly between the three definitions. The only consistent determinants among the three definitions were smaller lumen CSA at the reference site and larger plaque + media CSA at the lesion site. This study demonstrates the significant impact of different remodeling definitions on the incidence and determinants of remodeling patterns. The marked variability in categorization of remodeling underscores the importance of developing a standard methodology.