Genetic variants in haem oxygenase-1 and endothelial nitric oxide synthase influence the extent and evolution of coronary artery atherosclerosis.

The genetic basis for atherosclerosis development and progression is poorly characterized. We aimed to assess the relationship between endothelial nitric oxide synthase (ENOS) 894 G/T, haem oxygenase-1 (HO1) dinucleotide-length promoter polymorphisms and coronary artery atherosclerotic invol vement and its changes during statin therapy. Coronary angiography, intravascular ultrasound (IVUS), IVUS-derived virtual histology (VH) and genetic polymorphism analysis were performed at study entry. Patients were randomized 1:1 to standard or aggressive hypolipidaemic treatment, and a follow-up evaluation was performed after twelve months. Plaque magnitude was significantly higher in carriers of HO1 risk variants when compared with carriers of the protective variants (< 25 GT repeats). Similarly, the total coronary atherosclerotic burden was significantly greater in HO1 risk variant carriers than in HO1 protective variant carriers. Both parameters did not differ with respect to the ENOS genotype. A higher prevalence of thin-cap fibroatheroma (TCFA) in HO1 risk variant carriers was observed, compared with the HO1 protective variant carriers. The prevalence of TCFA was not influenced by the ENOS genotype. Baseline plaque composition did not differ significantly with respect to both polymorphisms. Significant interactions between plaque composition changes and ENOS and HO1 genotypes were observed during statin treatment. In conclusion, the protective HO1 promoter polymorphism correlates with a lower coronary artery plaque burden, whereas the protective ENOS 894 G/T polymorphism seems to favourably influence changes of coronary artery plaque composition during statin therapy, but has no significant correlation to the magnitude of coronary atherosclerosis.

Intravascular ultrasound assessment of coronary artery involvement in Fabry disease.

AIM: We used intravascular ultrasound (IVUS) to characterize coronary artery involvement in patients with Fabry disease (FD). METHODS: Nine FD patients (5 women) were matched to 10 control patients (5 women) chosen from our IVUS database. Standard volumetric IVUS analyses were performed along with assessment of plaque echodensity. RESULTS: Plaques in FD patients were diffuse and hypoechogenic compared with more focal and more echogenic lesions in control patients. Echogenicity of plaques was significantly lower in FD patients (median 30.7 +/- 12.9 vs 55.9 +/- 15.7, p = 0.0052, mean 37.2 +/- 15.6 vs 66.2 +/- 13.3, p = 0.0014). Diffusiveness was assessed as differences between mean and median plaque burden versus the plaque burden in each of the analysed cross-sections. These differences were lower in FD vs controls (5.8 +/- 4.8 vs 8.7 +/- 6.6, p < 0.001 for mean, and 5.8 +/- 4.9 vs 8.8 +/- 7.3, p < 0.001 for median) indicating a more diffuse involvement. The occurrence of lipid cores was significantly higher in FD patients than in controls (2.4 +/- 1.5 vs 1.0 +/- 0.94, p = 0.02). CONCLUSION: IVUS showed diffuse hypoechogenic plaques in patients with FD. The explanation may be higher lipid content in plaques and accumulation of glycosphingolipid in smooth-muscle and endothelial cells.

Mechanism of lumen enlargement with direct stenting versus predilatation stenting: influence of remodelling and plaque characteristics assessed by volumetric intracoronary ultrasound.

OBJECTIVE: To compare the effects of arterial remodelling and plaque characteristics on the mechanisms of direct stenting and predilatation stenting. Direct stenting has become routine in some laboratories and differs technically from predilatation stenting. METHODS: Pre- and post-interventional volumetric intravascular ultrasound (IVUS) was undertaken in 30 patients with direct stenting and in 30 with predilatation stenting of non-calcified native coronary lesions, using the same stent design and stent length. Lumen, vessel (external elastic membrane (EEM)), and plaque (plaque + media) volumes were calculated. Remodelling was determined by comparing the EEM area at the centre of the lesion with the EEM areas at proximal and distal reference sites. Plaque eccentricity was defined as the thinnest plaque diameter to the thickest plaque diameter ratio. Plaque composition was characterised as soft, mixed, or dense. RESULTS: All volumetric IVUS changes were similar in the two groups. Pre-intervention remodelling remained uninfluenced after direct stenting, but was neutralised after predilatation stenting. Eccentric lesions responded to intervention by a greater luminal gain owing to greater vessel expansion in direct stenting. Plaque composition influenced luminal gain in direct stenting, the gain being greatest in the softest plaques; in predilatation stenting, luminal gain was equivalent but vessel expansion was greater for "dense" plaque and plaque reduction greater for "soft" plaque. CONCLUSIONS: In non-calcified lesions, the mechanisms of lumen enlargement after direct or predilatation stenting are significantly influenced by atherosclerotic remodelling, plaque eccentricity, and plaque composition.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

The contribution of "mechanical" problems to in-stent restenosis: An intravascular ultrasonographic analysis of 1090 consecutive in-stent restenosis lesions.

OBJECTIVES: Serial intravascular ultrasonographic (IVUS) studies have shown that in-stent restenosis is the result of intimal hyperplasia (IH). However, routine preintervention IVUS imaging has suggested that many restenotic stents were inadequately deployed. The purpose of this IVUS study was to determine the incidence of mechanical problems contributing to in-stent restenosis (ISR). METHODS: Between April 1994 and June 2000, 1090 patients with ISR were treated at the Washington Hospital Center. All underwent preintervention IVUS imaging. IVUS measurements included proximal and distal reference lumen areas and diameters; stent, minimum lumen, and IH (stent minus lumen) areas; and IH burden (IH/stent area). RESULTS: In 49 ISR lesions (4.5%), there were morphologic findings that contributed to the restenosis. These were termed mechanical complications. Examples include (1) missing the lesion (eg, an aorto-ostial stenosis), (2) stent "crush," and (3) having the stent stripped off the balloon during the implantation procedure. Excluding mechanical complications, stent underexpansion was common. In 20% of the ISR cases the stents had a cross-sectional area (CSA) at the site of the lesion <80% of the average reference lumen area. Twenty percent of lesions had a minimum stent area <5.0 mm(2) and an additional 18% had a minimum stent area of 5.0 to 6.0 mm(2). Twenty-four percent of lesions had an IH burden <60%. CONCLUSION: Mechanical problems related to stent deployment procedures contribute to a significant minority of ISR lesions (approximately 25%).

The impact of high pressure vs low pressure stent implantation on intimal hyperplasia and follow-up lumen dimensions; results of a randomized trial.

AIMS: Histology and retrospective clinical studies have indicated that the amount of neointimal hyperplasia is dependent on the arterial injury induced during stent implantation. This study analysed, prospectively, the impact of high vs low pressure stent implantation techniques using a second generation stent on intimal hyperplasia and follow-up lumen dimensions. METHODS AND RESULTS: Post-intervention and follow-up (mean[+/-SD] 5.5+/-1.3 months) angiographic and intravascular ultrasound studies were performed on 120 Multi-Link HP stents randomized to implantation at either low (8-10 atm) or high (16-20 atm) pressure. Intravascular ultrasound measurements of the external elastic membrane, stent, and lumen cross-sectional area were performed at 1 mm axial increments. Peri-stent plaque+media cross-sectional area (external elastic membrane-stent cross-sectional area, intimal hyperplasia cross-sectional area (stent-lumen cross-sectional area at follow-up), intimal hyperplasia thickness and peri-stent tissue growth cross-sectional area (Deltapersistent plaque+media cross-sectional area) were calculated. Intravascular ultrasound demonstrated a larger minimal lumen cross-sectional area post-intervention in the high pressure group (7.3+/-2.0 vs 6.2+/-1.8 mm(2), P<0.001, high vs low pressure group, respectively). At follow-up, the mean intimal hyperplasia cross-sectional area (1.7+/-0.9 vs 1.5+/-0.8 mm(2), P=0.708), the mean intimal hyperplasia thickness (0.16+/-0.12 vs 0.16+/-0.12 mm, P=0.818) and peri-stent tissue proliferation cross-sectional area were not greater in the high pressure group. Thus, the minimal lumen cross-sectional area at follow-up continued to be greater (5.5+/-2.0 vs 4.7+/-1.7 mm(2), P=0.038) in the high pressure group. CONCLUSIONS: High pressure stent implantation results in greater stent expansion even with the less rigid second generation Multi-Link stent. Larger lumen dimensions persist at follow-up, while intimal hyperplasia is not significantly greater after high pressure implantation compared to the low pressure technique.

Elective stenting of unprotected left main coronary artery stenosis: effect of debulking before stenting and intravascular ultrasound guidance.

OBJECTIVES: We sought to evaluate: 1) the long-term outcomes of 127 selected patients receiving unprotected left main coronary artery (LMCA) stenting; and 2) the impact of the debulking procedure before stenting and intravascular ultrasound (IVUS) guidance on their clinical outcomes. BACKGROUND: The long-term safety of stenting of unprotected LMCA stenoses has not been established yet. METHODS: A total of 127 consecutive patients with unprotected LMCA stenosis and normal left ventricular function were treated by elective stenting. The long-term outcomes were evaluated between two groups: IVUS guidance (n = 77) vs. angiographic guidance (n = 50); and debulking plus stenting (debulking/stenting; n = 40) vs. stenting only (n = 87). RESULTS: Angiographic restenosis was documented in 19 (19%) of 100 patients. The lumen diameter after stenting was significantly larger in IVUS-guided group (p = 0.003). The angiographic restenosis rate was significantly lower in the debulking/stenting group (8.3% vs. 25%, p = 0.034). The reference artery size was the only independent predictor of angiographic restenosis. During follow-up (25.5 +/- 16.7 months), there were four deaths, but no nonfatal myocardial infarctions occurred. The survival rate was 97.0 +/- 1.7% at two years. CONCLUSIONS: These data suggest that stenting of unprotected LMCA stenosis might be associated with a favorable long-term outcome in selected patients. Guidance with IVUS may optimize the immediate results, and debulking before stenting seems to be effective in reducing the restenosis rate. However, we need a large-scale, randomized study.

An intravascular ultrasound classification of angiographic coronary artery aneurysms.

The purpose of this study was to use intravascular ultrasound (IVUS) to clarify the morphology of coronary aneurysms diagnosed by angiography. Seventy-seven consecutive patients with an aneurysmal dilatation in a native coronary artery diagnosed by angiography (defined as a lesion lumen diameter 25% larger than reference) were evaluated by IVUS. IVUS true aneurysms were defined as having an intact vessel wall and a maximum lumen area 50% larger than proximal reference. IVUS pseudoaneurysms had a loss of vessel wall integrity and damage to adventitia or perivascular tissue. Complex plaques were lesions with ruptured plaque or spontaneous or unhealed dissection. Aneurysmal dilatation and reference segments were assessed using standard IVUS quantitative techniques. Twenty-one lesions (27%) were classified as true aneurysms, 3 (4%) were classified as pseudoaneurysms, 12 (16%) were complex plaques, and the other 41 (53%) were normal arterial segments adjacent to > or =1 stenosis. The maximum lumen area within the aneurysmal segment was largest for pseudoaneurysm (35.1 +/- 10.4 mm(2)), 22.1 +/- 9.9 mm(2) for true aneurysm, and similar for complex plaques (11.2 +/- 3.5 mm(2)) and normal segments with adjacent stenoses (13.8 +/- 6.4 mm(2)): analysis of variance, p <0.0001. Only one third of angiographically diagnosed aneurysms had the IVUS appearance of a true or pseudoaneurysm. Instead, most angiographically diagnosed aneurysms had the morphology of complex plaques or normal segments with adjacent stenoses.

Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma-radiation therapy for preventing recurrence in very long, diffuse, in-stent restenosis lesions.

BACKGROUND: The efficacy of coronary gamma-irradiation in preventing recurrent in-stent restenosis (ISR) is well established. However, brachytherapy may be less effective in very long, diffuse ISR lesions. METHODS AND RESULTS: We used serial intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of intracoronary gamma-irradiation (15 Gy at 2 mm from the source) and (2) high-dose (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen, and intimal hyperplasia were measured at 2-mm intervals. Complete postintervention and follow-up IVUS imaging was available in 30 irradiated and 34 placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent length was longer in HD Long WRIST than in placebo or treated patients in Long WRIST (P=0.0064 and P=0.0125, respectively). Otherwise, baseline measurements were similar. At follow-up, the minimum lumen area was largest in the HD Long WRIST patients (4.0+/-1.4 mm(2)); areas were 2.9+/-1.0 mm(2) in irradiated patients in Long WRIST and 1.9+/-1.1 mm(2) in placebo patients in Long WRIST (P<0.005 for all comparisons). CONCLUSIONS: - Serial IVUS analysis shows that gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.

Intravascular ultrasound-guided renal artery stenting.

PURPOSE: To evaluate the clinical outcomes of patients undergoing renal artery stenting with intravascular ultrasound (IVUS) guidance and compare measurements between IVUS and angiography. METHODS: One hundred thirty-one patients (71 women; mean age 71 +/- 8 years) underwent IVUS-guided Palmaz stent implantation in 153 stenotic renal arteries at a single center. The indications for stenting were uncontrolled hypertension (102, 77.9%), renal insufficiency (10, 7.6%), and both conditions (19, 14.5%). The majority of lesions were ostial (114, 74.5%); the remainder occupied the proximal renal artery (39, 25.5%). The mean lesion length and diameter stenosis were 6.5 +/- 3.0 mm and 74% +/- 10%, respectively, as measured by angiography. Data were recorded in a prespecified database; angiographic and IVUS images were analyzed at dedicated core laboratories and compared. RESULTS: Angiographic success was achieved in all patients, but IVUS indicated the need for additional intervention in 36 (23.5%) cases. There was strong correlation between the angiographic and IVUS measurements of lesion length (r = 0.60, p < 0.0001) and pre-/postprocedural minimal luminal diameter (r = 0.72 and 0.63, respectively; p < 0.0001). The mean contrast volume was 74 +/- 18 mL per case. In-hospital renal failure occurred in 8 (6.1%) patients; 2 (1.5%) required transient hemodialysis. At a mean 15-month follow-up, patients were treated with fewer antihypertensive medications (p = 0.05), and systolic and diastolic arterial blood pressures had decreased (p = 0.001); no significant change was noted in serum creatinine. CONCLUSIONS: IVUS-guided stenting facilitates safe renal artery revascularization. IVUS imaging may complement angiography in certain cases, which should be studied further in prospective studies with iodinated or noniodinated contrast agents.

Are we making progress with percutaneous saphenous vein graft treatment? A comparison of 1990 to 1994 and 1995 to 1998 results.

OBJECTIVES: We sought to determine whether strategies to reduce procedural distal embolization and late repeat revascularization have resulted in more favorable outcomes after saphenous vein graft (SVG) angioplasty. BACKGROUND: Angioplasty of SVG lesions has been associated with frequent procedural and late cardiac events. Therefore, evolving strategies have been attempted to improve outcomes after SVG angioplasty. METHODS: We compared our earlier experience (1990 to 1994) of 1,055 patients with 1,412 SVG lesions with a recent group (1995 to 1998) of 964 patients with 1,315 lesions. RESULTS: Baseline characteristics were similar between the groups. However, there were significantly more unfavorable lesion characteristics (older, longer and significantly more degenerated SVGs) in the recent series. Between the two periods, there was decreased use ofatheroablative devices, whereas stent use increased. The procedural success rates (96.6% vs. 96.1%) were similar. However, one-year outcome (event-free survival) was significantly improved in the more recent experience (70.7% vs. 59.1%, p < 0.0001), especially late mortality (6.1% vs. 11.3%, p < 0.0001). Multivariate analysis showed stent use to be the only protective variable for both periods. CONCLUSIONS: This study shows that despite higher risk lesions, strategies to reduce distal embolization have maintained high procedural success. Late cardiac events, including mortality, have also been substantially reduced.

Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population.

Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 +/- 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 +/- 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 +/- 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.

Intravascular ultrasound assessment of the stenoses location and morphology in the left main coronary artery in relation to anatomic left main length.

Eighty-seven left main stenoses were evaluated by angiography and intravascular ultrasound. Intravascular ultrasound analysis included left main length (bifurcation to ostium), stenosis location, stenosis length, stenosis external elastic membrane, lumen, plaque & media cross-sectional area (CSA), plaque burden (plaque & media/external elastic membrane CSA), calcium arc, calcium length, eccentricity, and remodeling index (stenosis/reference external elastic membrane CSA). Long anatomic left main arteries (length > or =10 mm, n = 43) were compared with short anatomic left main arteries (length <10 mm, n = 44) regarding stenosis location. Ostial (proximal third of left main artery) (n = 32) and nonostial (midthird and distal third) stenoses (n = 55) were compared regarding stenosis morphology. Short anatomic left main arteries developed stenoses more frequently near the ostium (ostium 55%, bifurcation 38%). Conversely, long anatomic left main arteries developed stenoses more frequently near the bifurcation (ostium 18%, bifurcation 77%, p = 0.001). Ostial left main stenoses were more common in women (44% vs 20%, p = 0.02), had larger lumen area (6.2 +/- 2.2 vs 4.6 +/- 2.3 mm(2), p = 0.002), less plaque burden (62 +/- 15% vs 80 +/- 9%, p <0.0001), less calcification (arc = 78 +/- 65 degrees vs 195 +/- 101 degrees, p <0.0001), and more negative remodeling (remodeling index = 0.87 +/- 0.19 vs 1.01 +/- 0.21, p = 0.005) than nonostial left main stenoses. Most ostial left main stenoses were categorized as eccentric (97% vs 76%, p = 0.01). Short and long left main arteries develop stenoses at different locations. Stenosis morphology was significantly different in these 2 locations.

Plaque distribution and vascular remodeling of ruptured and nonruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo.

OBJECTIVES: This study was designed to identify potential differences between the intravascular ultrasound (IVUS) characteristics of spontaneously ruptured and nonruptured coronary plaques. BACKGROUND: The identification of vulnerable plaques in vivo may allow targeted prevention of acute coronary events and more effective evaluation of novel therapeutic approaches. METHODS: Intravascular ultrasound was used to identify 29 ruptured plaques in arteries containing another nonruptured plaque in an adjacent segment. Intravascular ultrasound characteristics of these plaques were compared with plaques of computer-matched controls without evidence of plaque rupture. Plaque distribution was assessed by measuring the eccentricity of lumen location (inside the total vessel). Lumen cross-sectional area narrowing was calculated as [1 - (target/reference lumen area)] x 100%. A remodeling index was calculated as lesion/reference arterial area (>1.05 = compensatory enlargement, <0.95 = shrinkage). RESULTS: Among the three groups of plaques, there was no significant difference in quantitative angiographic parameters, IVUS reference dimensions and IVUS lumen cross-sectional area narrowing. There was a difference in plaque distribution; lumen location by IVUS was significantly more eccentric in ruptured than in nonruptured (p = 0.002) and control plaques (p < 0.0001). The arc of disease-free vessel wall was larger in ruptured than in control plaques (p < 0.0001). The remodeling pattern of ruptured and nonruptured plaques differed significantly from that of the control plaques (p = 0.0001 and 0.003); compensatory enlargement was found in 66%, 48%, and 17%, whereas shrinkage was found in 7%, 10% and 48%, respectively. CONCLUSIONS: Intravascular ultrasound assessment of plaque distribution and vascular remodeling may help to classify plaques with the highest probability of spontaneous rupture.

Intracoronary radiation with gamma wire inhibits recurrent in-stent restenosis.

To study the safety and efficacy of intracoronary gamma radiation delivered via a new high-activity (192)Ir source wire for the treatment of in-stent restenosis. In-stent restenosis results from neointimal tissue proliferation especially in its diffused form and presents a therapeutic challenge. Gamma radiation has been shown to decrease neointima formation within stents in animal models and in initial clinical trials. A total of 26 patients with in-stent restenosis underwent successful intervention and was treated with open-label (192)Ir using a high-activity line source. The specific activity of the source wire was 372+/-51 mCi, and the dwell time was 10.8+/-1.9 min. Primary endpoints were freedom from death, myocardial infraction (MI), and repeat target lesion revascularization (TLR) at 6 months. Secondary endpoints included angiographic restenosis and intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was high (96.2%), and in-hospital and 30-day complications were low with no deaths, MI, or requirement for repeat revascularization. At 6 months, event-free survival was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21) in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25 patients. There was no increase in intimal hyperplasia from postintervention to follow-up (3.11.8 vs. 3.41.8 mm(2); P=.32). Eight patients had a reduction of neointimal intimal tissue at follow-up. These results indicate that intracoronary gamma radiation with the Angiorad source wire is safe and effective in preventing in-stent restenosis.

Serial intravascular ultrasound analysis of edge recurrence after intracoronary gamma radiation treatment of native artery in-stent restenosis lesions.

In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients were first treated with conventional techniques and then randomized to either gamma-irradiation ((192)Ir) or placebo (dummy seeds). In the (192)Ir group with native coronary in-stent restenosis, we identified 8 patients with edge recurrence and compared them with 21 patients with no recurrence. Serial (postirradiation and follow-up) intravascular ultrasound analysis was performed according to conventional methods. When compared with nonrecurring lesions, lesions with distal edge recurrence had (1) greater decrease in mean distal lumen cross-sectional area (-3.0 +/- 1.2 vs -0.7 +/- 1.0 mm(2), p = 0.0002), (2) no change in mean distal external elastic membrane cross-sectional area versus an increase in mean distal cross-sectional area of 1.0 +/- 0.9 mm(2) in nonrecurring lesions (p = 0.0047), and (3) a greater increase in mean distal plaque + media cross-sectional area (2.9 +/- 1.2 mm vs 1.7 +/- 0.6 mm(2), p = 0.0103). Within the stented segment, the nonrecurring lesions had no decrease in mean lumen and no increase in mean intimal hyperplasia cross-sectional area. Conversely, lesions with distal edge recurrence had a significant decrease in mean intrastent lumen cross-sectional area (-1.7 +/- 1.7 mm(2)) and a significant increase in mean intrastent intimal hyperplasia cross-sectional area (1.6 +/- 1.6 mm(2)). Lesions with distal edge recurrence also had a greater decrease in mean proximal lumen cross-sectional area (-1.7 +/- 1.3 vs -0.3 +/- 0.8 mm(2), p = 0.0213), with a trend toward a greater increase in mean proximal plaque + media cross-sectional area. Thus, edge recurrence after (192)Ir treatment of in-stent restenosis is the result of neointimal hyperplasia (part of generalized treatment failure) and the absence of radiation-induced positive remodeling.