Heidi N. Bonneau

7-Hexanoyltaxol–Eluting Stent for Prevention of Neointimal Growth: An Intravascular Ultrasound Analysis From the Study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE)

Background—Inhibition of neointimal tissue growth has been demonstrated in preliminary human feasibility studies with a stent-based polymer sleeve delivering 7-hexanoyltaxol. The Study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE) trial is a human, randomized, multicenter trial comparing 7-hexanoyltaxol (QP2)-eluting stents (qDES) with bare metal stents (BMS) in the treatment of de novo coronary lesions. The purpose of this substudy was to evaluate the acute expansion property and long-term neointimal responses of qDES compared with BMS as assessed by intravascular ultrasound (IVUS). Methods and Results—A total of 122 (qDES 66, BMS 56) patients were enrolled into the IVUS substudy. All IVUS images (immediately after the procedure and at 6-month follow-up) were analyzed at an independent core laboratory in a blind manner. At baseline, qDES achieved stent expansion similar to BMS. At follow-up, qDES showed reduced neointimal growth by 70% at the tightest cross section and by 68% over the stented segment (P <0.0001 for both), resulting in a significantly larger lumen in qDES than in BMS. Unlike intracoronary brachytherapy, there was no evidence of negative edge effects, unhealed dissections, or late stent-vessel wall malapposition over the stented and adjacent references segments in either group. Conclusions—Detailed IVUS analysis revealed that qDES had comparable acute mechanical and superior long-term biological effects to BMS. Although the long-term benefits and limitations of this technology require further investigation, the reduction in neointimal thickenings demonstrated that local delivery of 7-hexanoyltaxol through polymer sleeves augments conventional mechanical treatment of atherosclerotic disease.

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.

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

BackgroundVessel 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 ResultsSerial 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 [%&Dgr;]). As expected, %&Dgr;PSV directly correlated with %&Dgr;VV (P <0.0001, r =0.935), with no significant &Dgr;SV. A highly significant inverse correlation was seen between %&Dgr;PSV and the percent change of intrastent volume (P <0.0001, r =0.517). Consequently, %&Dgr;LV significantly correlated with peri-stent remodeling, as measured by %&Dgr;VV (P <0.0001, r =0.602). ConclusionPositive 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.

An optimal diagnostic threshold for minimal stent area to predict target lesion revascularization following stent implantation in native coronary lesions.

tions, 1980:122–159. 17. Antoniucci D, Valenti R, Moschi G, Santoro GM, Bolognese L, Trapani M, Fazzini PF. Cost-effective analysis of primary infarct-artery stenting versus optimal primary angioplasty (the Florence Randomized Elective Stenting in Acute Coronary Occlusions [FRESCO] trial). Am J Cardiol 2000;85:1247–1249. 18. Saito S, Hosokawa G. Primary Palmaz-Schatz stent implantation for acute myocardial infarction: the final results of Japanese PASTA (primary angioplasty vs stent implantation in AMI in Japan) trial (abstr). Circulation 1997;96(suppl I):I-595. 19. Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA, Giambartolomei A, Brodie BR, Lansky AJ, O’Neill WW, Grines LL, Boura JA, Morice MC. Stent PAMI. 12 month results and predictors of mortality. J Am Coll Cardiol 2000; 35(suppl A):402A. 20. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992;14:154–176.

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.

AUTOMATED CONTOUR DETECTION FOR HIGH-FREQUENCY INTRAVASCULAR ULTRASOUND IMAGING: A TECHNIQUE WITH BLOOD NOISE REDUCTION FOR EDGE ENHANCEMENT

Automated edge detection may standardize measurements among observers, providing for rapid assessment of intravascular ultrasound (IVUS) images. However, with high frequency images, enhanced blood signals make it difficult to define and trace the lumen borders. Accordingly, we evaluated a fully automated contour analysis facilitated with a blood noise reduction algorithm (BNR) for 40-MHz IVUS images in human coronary arteries of 27 patients. This algorithm is based on the principle that blood echo speckles have higher temporal and spatial variations than the arterial wall. A total of 193 paired lumen areas and 78 external elastic membrane (EEM) areas were measured and compared. Automated measurements showed good agreement with manual tracings for lumen and EEM area, with high correlation coefficients (0.945 and 0.950, respectively) and small variability (0.4 +/- 14.4% and 0.6 +/- 9.7%, respectively). This preliminary finding suggests that automated contour detection facilitated with BNR appeared to be a feasible and reliable technique for area measurements in 40-MHz IVUS imaging.

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 Simpsons 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.

Mechanisms of acute lumen gain following cutting balloon angioplasty in calcified and noncalcified lesions: An intravascular ultrasound study

Several studies have shown that mechanisms for lumen enlargement following conventional balloon angioplasty (BA) consist of plaque reduction and vessel expansion. To assess the mechanisms of lumen enlargement after Cutting Balloon (CB) angioplasty, intravascular ultrasound images were analyzed in 180 lesions (89 CB and 91 BA). External elastic membrane (EEM) cross‐sectional area (CSA), lumen CSA, and plaque plus media (P+M) CSA were measured before and after angioplasty. In the CB group, lower balloon pressure was utilized (P < 0.0001). ΔP+M CSA was significantly larger (P = 0.02) and Δlumen CSA showed a trend toward being larger (P = 0.07) compared to BA group. For noncalcified lesions, CB resulted in a larger ΔP+M CSA (P < 0.05) and a smaller ΔEEM CSA (P = 0.10) than BA. For calcified lesions, Δlumen CSA was significantly larger in the CB group (P < 0.05) without significant differences in ΔEEM CSA and ΔP+M CSA. Dissections complicated with calcified lesions were associated with larger Δlumen CSA for the CB group. In conclusion, for noncalcified lesions, CB achieves similar luminal dimensions with larger plaque reduction and less vessel expansion compared to BA. On the other hand, for calcified lesions, the CB achieves larger lumen gain, especially in lesions with evidence of dissections. Cathet Cardiovasc Intervent 2002;57:429–436.

Delivered Dose and Vascular Response After β-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 90Sr/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 ≤3.35 mm and 23 Gy for diameter ≥3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). DS90EEM (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 DS90EEM 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 90Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.

Influence of plaque calcium on neointimal hyperplasia following bare metal and drug-eluting stent implantation

To examine the influence of vessel wall calcium on neointimal hyperplasia (NIH) following bare metal stent (BMS) and drug‐eluting stent (DES) implantation.