Follow-up Intravascular Ultrasound Research Articles

Mechanisms and Predictors of Carotid Artery Stent Restenosis: A Serial Intravascular Ultrasound Study

The aim of this study was to determine the mechanisms and predictors of carotid artery restenosis after carotid artery stenting (CAS) using serial intravascular ultrasound (IVUS) imaging. Carotid artery stenting is increasingly used to treat high-grade obstructive carotid disease, but our knowledge of carotid in-stent restenosis and remodeling remains limited. Post-procedural and 6-month (median 6 months) follow-up quantitative carotid angiography and IVUS were performed after self-expanding stent deployment in 50 internal carotid arteries (ICA). The IVUS measurements at multiple designated sites included minimal luminal diameter, lumen area, stent area (SA), and neointimal hyperplasia area (NIH). Late stent enlargement at follow-up was found at all segments, and the percentage increase was greatest at the ICA lesion site (mean +/- SD, 48.9 +/- 35.3%). The NIH, expressed as a percentage of SA, was seen within all segments of the stent and was greatest at the ICA lesion site (37.3 +/- 23.3%). There was a strong positive correlation between the amount of NIH and late stent enlargement (r = 0.64; p < 0.001). Immediate post-procedural minimum ICA SA (r = -0.37; p < 0.01) and stent expansion (r = -0.44; p = 0.001) correlated negatively with the percentage restenotic area at follow-up. Although self-expanding carotid stents generate considerable neointimal hyperplasia, the process is balanced by marked late stent enlargement. Small stent dimensions immediately post-procedure were associated with a higher risk of restenosis.

Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: Effects of statin therapy on ruptured coronary plaque

Using serial intravascular ultrasound (IVUS), we evaluated the natural evolution of non-culprit/non-target lesion ruptured coronary plaques and assessed the impact of statin therapy. Twenty-eight patients with non-stenotic ruptured plaques underwent baseline and 12-month follow-up IVUS studies; half were treated with statins. Standard IVUS analyses were performed. Complete healing of ruptured plaques was observed in four (29%) statin-treated patients and no non-statin-treated patients ( p = 0.049). Statin-treated patients had an increase in lumen area of 0.4 ± 0.8 mm 2 (versus a decrease in lumen area of −0.6 ± 1.0 mm 2 in non-statin-treated patients, p = 0.007) and no change in plaque area (versus an increase in plaque area of 0.6 ± 0.9 mm 2, p = 0.051). During 1-year follow-up, target lesion revascularization was performed in three non-statin-treated patients (21%) and no statin-treated patient ( p = 0.11). Compared to lesions that did not require revascularization, lesions requiring revascularization had a decrease in lumen area (−1.7 ± 1.4 mm 2 versus 0.1 ± 0.8 mm 2, p = 0.001) as well as an increase in plaque area (1.6 ± 1.0 mm 2 versus 0.1 ± 0.7 mm 2, p = 0.002). In conclusion, the current observational follow-up IVUS study showed beneficial effects of statin treatment on reduction of revascularization rates and stabilization of non-culprit/non-target lesion plaque ruptures without significant stenosis. Conversely, healing of non-statin-treated non-culprit/non-target lesion plaque ruptures can be responsible for lesion progression requiring revascularization.

Invited commentary

This report [1] provides extensive angiographic and intravascular ultrasound follow-up of patients having coronary ostial and left main (LM) angioplasty with a patch of the proximal right internal thoracic artery (ITA) and demonstrating excellent anatomic results at 7 to 79 months postoperatively.

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.

Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis

Prior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression. To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging. Prospective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion. Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations. All patients received intensive statin therapy with rosuvastatin, 40 mg/d. Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified. The mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was -0.98% (3.15%), with a median of -0.79% (97.5% CI, -1.21% to -0.53%) (P<.001 vs baseline). The mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was -6.1 (10.1) mm3, with a median of -5.6 mm3 (97.5% CI, -6.8 to -4.0 mm3) (P<.001 vs baseline). Change in total atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of -14.7 (25.7) mm3, with a median of -12.5 mm3 (95% CI, -15.1 to -10.5 mm3) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials. Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome. ClinicalTrials.gov Identifier: NCT00240318.

Compensatory enlargement of human coronary arteries during progression of atherosclerosis is unrelated to atheroma burden: serial intravascular ultrasound observations from the REVERSAL trial

On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement (remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden (cross-sectional area stenosis) reaches approximately 40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound (IVUS). From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane (EEM) area for each mm(2) increase in atheroma area was not significantly different in lesions with <40 and >or=40% atheroma burden at baseline (1.62 vs. 1.28 mm(2), P=0.30). There were no correlations between atheroma burden at baseline and change in EEM (r=0.02, P=0.86) or change in lumen (r=0.04, P=0.64) areas. Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.

Paradoxical increase in lumen size during progression of coronary atherosclerosis: Observations from the REVERSAL trial

Relative changes in lumen size during progression and regression of coronary atherosclerosis remain largely unknown. We assessed these changes using serial intravascular ultrasound (IVUS). From the baseline IVUS interrogations of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, 210 focal coronary lesions with <50% angiographic stenosis were identified. Lesions were matched to the follow-up IVUS, performed after 18 months of treatment with atorvastatin 80 mg/day or pravastatin 40 mg/day. Changes in external elastic membrane (EEM) and lumen areas of lesions demonstrating progression and regression (i.e. increased and decreased atheroma area) were examined. In progressors ( n = 128), there was 1.34 mm 2 increase in EEM area for every 1 mm 2 increase in atheroma area ( r = 0.72, p < 0.0001). This resulted in 0.34 mm 2 increase in lumen area for every 1 mm 2 increase in atheroma area ( r = 0.25, p = 0.004). In contrast, there was no significant change in lumen area with regression of disease ( n = 82, r = −0.06, p = 0.59). Progression of coronary atherosclerosis can be associated with a paradoxical increase in lumen cross-sectional area, whereas regression is not associated with any change in lumen area. Measurement of changes in lumen size may not be an accurate method to study progression and regression of atherosclerotic lesions with <50% stenosis.

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.

Intravascular Ultrasound Characterization of the “Black Hole” Phenomenon After Drug-Eluting Stent Implantation

An intraluminal echolucent tissue, dubbed "black hole," has been identified by intravascular ultrasonography after intracoronary brachytherapy. This study reports the characteristics and incidence of the black hole in patients treated with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We included intravascular ultrasound data from the Compassionate Use of Sirolimus-Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions), a multicenter, randomized study comparing SES versus bare metal stents in diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In the SECURE population, a black hole was observed in 10 patients (19.6%). Seven black hole segments had significant intimal hyperplasia (> 10%). A black hole accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients (2.5%) in the SES group and none in the bare metal stent group showed echolucent intimal hyperplasia. In conclusion, a black hole occurred frequently after implantation of a SES in patients in whom intracoronary brachytherapy had previously failed. Black holes were also identified in a nonirradiated population, although the incidence was lower than in the post-brachytherapy patients. Bare metal stents were not associated with this phenomenon.

Preinterventional peak monocyte count and in-stent intimal hyperplasia after coronary stent implantation in human coronary arteries

The mechanism of restenosis after stent implantation principally is neointimal hyperplasia. There is evidence that monocytes play a important role in in-stent restenosis (ISR) after stent implantation. This study assessed the relationship between preinterventional peak monocyte count and neointimal growth after successful stent implantation. We performed coronary stent implantation in 85 patients (85 de novo lesions). Peripheral blood sample was obtained in all patients every 12 h before coronary angiography for measurement of peripheral monocytes. All patients received angiographic and intravascular ultrasound (IVUS) follow-up at 6 months after stenting. The preinterventional circulating monocyte count was significantly higher in the ISR group than that in the group without ISR (654 +/- 62/vs. 461 +/- 222/mm3, p < 0.001) and was significantly higher in the reintervention group than that in the no-reintervention group (660 +/- 72/ vs. 470 +/- 216/mm3, p< 0.001). The incidence of ISR and repeat intervention associated with preinterventional monocyte count was highest among the patients in the highest tertile, who were at a 2.64-fold increased risk of ISR and 3.22-fold increased risk of repeat intervention compared with the patients in the lowest tertile. A significant positive correlation was found between preinterventional peak monocyte count and preinterventional plaque and media cross-sectional area and follow-up neointima area (r = 0.311, p = 0.007, r = 0.465, p < 0.001, respectively). The neointima area associated with preinterventional monocyte count was largest among the patients in the highest tertile, that is, 2-fold larger than that of the patients in the lowest tertile (p < 0.001) and 1.44-fold larger than that of the patients in the middle tertile (p = 0.001). Our results suggest that circulating preinterventional monocytes play a principal role in the process of in-stent neointimal growth after successful stent implantation.

Six-Month Intravascular Ultrasound Follow-up of Coronary Bifurcation Lesions Treated With Rapamycin-Eluting Stents: Technical Considerations

In vitro studies show that stents deform when dilated laterally to access a side branch. This phenomenon may be avoided by use of a kissing balloon at the end of the procedure. However, to date, no in vivo data are available. Our objectives were to investigate the main vessel stent using intravascular ultrasound (IVUS) at six-month follow-up in 55 patients with bifurcation lesions treated using rapamycin-eluting stents and to examine the effect of technical factors. All patients were treated using provisional or T stents. At 6 months, IVUS measurements were made in the main vessel at both proximal and distal ends of the stent, in reference segments, immediately below the side branch ostium, and at the points where the lumen was smallest and where stent expansion was greatest. The lumen area immediately below the side branch ostium was significantly smaller than that at the point of maximum stent expansion (6.7 [1.8] vs 5.1 [1.3] mm2; P<.05). Underexpansion was not influenced by use of a kissing balloon (stent area immediately under the side branch ostium: 5.5 [0.9] vs 5.6 [1.6] mm2; P=NS) and only one patient experienced restenosis at this point. The lumen areas at the proximal and distal edges of the stent were almost identical in patients who did or did not undergo balloon dilation beyond the ends of the stent. Stent underexpansion below the side branch ostium was frequently found following provisional or T stenting of bifurcation lesions. This minor stent deformity was not prevented by use of a kissing balloon nor by any specific side branch treatment and had no significant impact on the restenosis rate.

Comparison Between Sirolimus-Eluting Stents and Intracoronary Catheter-Based Beta Radiation for the Treatment of In-Stent Restenosis

We report the outcomes of patients who had in-stent restenosis (IRS) that was treated with intravascular brachytherapy (IVBT) or sirolimus-eluting stent (SES) implantation. The benefit of IVBT for treating ISR is well documented. SES implantation decreases first-time ISR and, in preliminary reports, has been used to treat ISR. Fifty consecutive patients who had ISR were treated; the first 25 patients underwent SES implantation and the next 25 patients were treated with IVBT using a beta-Cath System (a 40-mm strontium-90/yttrium-90 source). Quantitative angiographic and intravascular ultrasound follow-up were performed at 5.2 +/- 1.1 and 12.1 +/- 1.2 months; clinical follow-up was performed at 15 months. SES deployment and IVBT were successful in all patients. At 12-month follow-up, 8 patients who underwent IVBT had angiographic recurrence (4 in the stent and 4 at the stent edge); only 1 patient who underwent SES implantation developed recurrent ISR. At 12 months, in-stent late luminal loss was similar between the SES and IVBT groups (0.35 +/- 0.45 vs 0.34 +/- 0.46 mm, p = 0.9); however, in-stent net luminal gain was higher in the SES group than in the IVBT group (1.32 +/- 0.13 vs 0.57 +/- 0.19 mm, p <0.0001), and in-lesion late luminal loss was higher in the IVBT group (0.48 +/- 0.32 vs 0.16 +/- 0.42 mm, p = 0.004). At 12 months, intravascular ultrasound stent volume obstruction was higher after IVBT versus than after SES implantation (38.7% vs 6.7%, p <0.0001). At 15-month clinical follow-up, 64% and 96% (p <0.01) of patients who underwent IVBT and SES implantation, respectively, were free of major adverse cardiac events. In conclusion SES implantation for the treatment of ISR was effective and superior to catheter-based IVBT in preventing recurrent neointimal proliferation and angiographic restenosis at 1-year follow-up.

Four-Year Angiographic and Intravascular Ultrasound Follow-up of Patients Treated With Sirolimus-Eluting Stents

Four-Year Angiographic and Intravascular Ultrasound Follow-up of Patients Treated With Sirolimus-Eluting Stents

Four-Year Angiographic and Intravascular Ultrasound Follow-Up of Patients Treated With Sirolimus-Eluting Stents

Despite the proven superiority of sirolimus-eluting stents (SESs) compared with bare stents in the first year after implantation, long-term outcomes of patients treated with these novel devices remain unknown. Our goal was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with SESs 4 years after implantation. The study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR; n=15] and fast release [FR; n=15]). Twenty-six patients underwent 4-year angiographic and IVUS follow-up and had matched assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up). One death occurred during the study period in a patient with a patent SES. There were no target-vessel revascularizations or thromboses between 2- and 4-year follow-up examinations. There was no stent thrombosis, target-lesion revascularization, death, or myocardial infarction in the SR group up to 4 years. Cumulative event-free survival rate was 87% for the total population (80% in the FR group and 93% in the SR group). In-stent late loss was slightly greater in the FR group (0.41+/-0.49 mm) than the SR group (0.09+/-0.23) after 4 years. One patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FR=9.1% and SR=5.7%). This study confirms the longevity of the optimal outcomes observed in patients treated with sirolimus-eluting Bx Velocity stents 4 years after implantation. In-stent lumen dimensions remained essentially unchanged at 4-year follow-up, particularly in the population treated with the currently available SES (SR formulation).

Elevated Preprocedural High-Sensitivity C-Reactive Protein Levels are Associated With Neointimal Hyperplasia and Restenosis Development After Successful Coronary Artery Stenting

Recent data indicate that an elevated serum level of high-sensitivity C-reactive protein (hs-CRP) predicts the risk of recurrent coronary events, and that statin therapy decreases the risk of coronary events. This study assessed the relationship between the pre-procedural hs-CRP level and in-stent neointimal hyperplasia (NIH) after stenting and the effects of statins on the relationship between restenosis after stenting and the serum hs-CRP levels of patients with coronary artery disease. This study included 100 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a normal C-reactive protein (CRP) group (<0.5 mg/dl, n=59) and elevated CRP group (>or=0.5 mg/dl, n=41). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline CRP level was 0.29+/-0.08 mg/dl in the normal CRP group and 2.90+/-2.31 mg/dl in the elevated CRP group. The NIH cross-sectional area (CSA) in the minimal lumen CSA at follow-up was significantly larger in the elevated CRP group compared with the normal CRP group (1.9+/-1.3 mm2 vs 3.0+/-1.5 mm2, p=0.001). A significant positive correlation was found between pre-interventional CRP level and NIH area (r=0.52, p<0.001). In patients with normal CRP, an association between statin therapy and restenosis was not observed. However, when the analysis was confined to patients with elevated CRP, statin therapy significantly reduced the restenosis rate (20% vs 37.5%, p=0.031). In the normal CRP group, the intra-stent neointimal area at 6 months was not different between the non-statin and statin groups (2.2+/-1.4 mm2 vs 1.8+/-1.1 mm2). However, in the elevated CRP group, statin therapy significantly decreased the neointimal area at 6-month follow-up (3.6+/-1.7 mm2 vs 2.4+/-1.3 mm2, p<0.001). Measuring the pre-interventional hs-CRP level may help predict the development of restenosis after stenting and statin therapy will significantly reduce the restenosis rate in patients with an elevated hs-CRP.

First human experience with angiopeptin-eluting stent: A quantitative coronary angiography and three-dimensional intravascular ultrasound study

Angiopeptin has been shown to reduce in-stent restenosis in various animal models. Meanwhile, BiodivYsio DD phosphorylcholine (PC)-coated stent provides a platform for local delivery of antiproliferative agents to the coronary artery. We studied the feasibility, safety, and impact on tissue growth of angiopeptin-eluting BiodivYsio DD PC-coated stents in human native de novo coronary lesions. We enrolled 14 patients (16 lesions) who underwent intravascular ultrasound (IVUS)-guided angiopeptin-eluting stent implantation in native coronary arteries between 3.0 and 4.0 mm in diameter with lesion length<or=18 mm. We successfully implanted 13 stents loaded with 22 microg of angiopeptin and three stents with 126 microg of angiopeptin. No major adverse cardiac events or target vessel failure occurred at 1-year clinical follow-up. All patients underwent 6-month angiographic and volumetric IVUS follow-up. In-stent late loss was 0.46+/-0.32 mm in the low-dose group and 0.26+/-0.14 mm in the high-dose group. Binary restenosis rate was 0%. Follow-up percentage neointimal hyperplasia by IVUS was 18.4%+/-22.5% for the low-dose group and 10.2%+/-5.8% for the high-dose group, respectively. There were no edge effect and late stent malapposition. Angiopeptin-eluting BiodivYsio DD PC stent appears feasible and safe in treating native de novo coronary lesions with modest degree of neointimal hyperplasia.

Evolution of Spontaneous Atherosclerotic Plaque Rupture With Medical Therapy

Ruptured coronary atheromatous plaque is generally considered to involve a high risk of subsequent clinical events. Few data are available on the natural evolution of non-culprit-lesion ruptured plaque. We therefore used serial intravascular ultrasound (IVUS) to study how such lesions, detected in the context of a first acute coronary syndrome with elevated troponin I levels, develop. Fourteen patients with 28 distinct plaque ruptures (2+/-1 per patient) without significant associated stenosis (minimal lumen cross-sectional area >4 mm2) were included and systematically treated with 40 mg statin and antiplatelet agent (clopidogrel and aspirin for > or =9 months). Mean clinical and IVUS follow-up was 22+/-13 months (median, 22 months). No clinical event related to the lesion under study occurred. On final IVUS examination, half (14 of 28) of the ruptured plaques had healed, and the degree of stenosis tended to diminish (stenosis, 22+/-17% versus 29+/-17% at baseline; P=0.056). No healing-prediction criterion could be identified. Nearly 2 years of follow-up found that spontaneous coronary atheromatous plaque rupture without significant stenosis detected on first acute coronary syndrome healed without significant plaque modification in 50% of cases with medical therapy.

Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesionsThe Oral Rapamune to Inhibit Restenosis (ORBIT) study

The aim of this study was to establish safety and feasibility of oral Rapamycin at two doses—2 mg and 5 mg—in achieving low rates of repeat target lesion revascularization (TLR) in de novo native coronary artery lesions. Drug-eluting stents have shown the ability to limit restenosis. Oral Rapamycin is an alternative strategy that can target multiple coronary lesions suitable for treatment with any approved metal stent and at potentially lower cost. The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open-label study of 60 patients with de novo lesions treated with bare metal stents in up to two vessels. After a loading dose of 5 mg, patients received a daily dose of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic, intravascular ultrasound (IVUS), and clinical follow-up were conducted. Baseline clinical and procedural characteristics were similar: 10% of patients in the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the 2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up, late loss (0.6 ± 0.5 mm vs. 0.7 ± 0.5 mm; p = NS), in-stent binary restenosis (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs. 24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in 2-mg and 5-mg groups. Oral Rapamycin for the prevention of restenosis is safe, feasible, and associated with low rates of repeat revascularization. Although associated with certain side effects, it may be considered for patients undergoing multivessel stents if proven in larger randomized studies.

Actinomycin-eluting stent for coronary revascularizationA randomized feasibility and safety study: The ACTION trial

We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novonative coronary esions. Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 μg/cm 2 of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction. The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis.

Effect of abciximab-coated stent on in-stent intimal hyperplasia in human coronary arteries

The investigators tested whether abciximab-coated stents prevent neointimal hyperplasia (NIH) formation in coronary de novo lesions. Abciximab-coated stents were compared with control stents. All patients underwent follow-up coronary angiography and intravascular ultrasound (IVUS). All stents were successfully deployed, and patients were discharged home without clinical events. At follow-up coronary angiography, the restenosis rate and late loss were 14% and 0.33 +/- 0.28 mm in the abciximab-coated stent group and 28.6% and 0.64 +/- 0.32 mm in the control stent group (p = 0.099 and p = 0.014, respectively). At follow-up IVUS, the intrastent luminal area and intrastent NIH area were 5.7 +/- 1.6 and 2.0 +/- 1.6 mm(2), respectively, in the abciximab-coated stent group and 4.2 +/- 0.8 and 3.4 +/- 1.7 mm(2), respectively, in the control stent group (p = 0.001 and p = 0.001, respectively). Abciximab-coated stents are feasible and significantly inhibit NIH, with potential therapeutic benefit in preventing stent restenosis.