The atherosclerotic Yucatan animal model to study the arterial response after balloon angioplasty: the natural history of remodeling

OBJECTIVE: Remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference which, together with plaque growth or neointimal formation, determines the lumen of the artery. To better understand the fundamental biology of neointimal formation, remodeling and their interaction, animal studies are needed. In this study, we described in detail the methodology used and the natural history of neointimal formation and remodeling after balloon angioplasty in atherosclerotic Yucatan micropigs. METHODS AND RESULTS: Atherosclerosis was induced in 60 peripheral arteries of sixteen Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed in 38 arteries, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2, 4, 7, 14 or 42 days follow-up. Remodeling, expressed as late media-bounded area (MBA) loss, increased progressively over time. At 42 days, late MBA loss after balloon angioplasty was significantly different compared to late MBA loss in control arteries, 2.2 +/- 1.0 versus -0.3 +/- 1.1 mm2 and p = 0.02. Late lumen loss increased over time and was highest at 42 days after balloon angioplasty (2.8 +/- 0.7 mm2). The contribution of neointimal formation to late lumen loss decreased over time and the contribution of late MBA loss to late lumen increased over time and was highest at 42 days (78%). Medial necrosis was 48% at two days after balloon angioplasty and the repopulation of the media was almost completed at seven days. CONCLUSION: Remodeling following balloon angioplasty has an early onset and progresses with neointimal formation to cause restenosis over the standard 42-day time course for Yucatan micropigs. This correlates to six months renarrowing in humans. In this model, atherosclerosis and the natural history of restenosis, both with respect to neointimal formation and remodeling, resemble the human disease quite closely.     

The relation between de novo atherosclerosis remodeling and angioplasty-induced remodeling in an atherosclerotic Yucatan micropig model

Geometric remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference that, together with plaque growth or neointima formation, determines the lumen of the artery. The heterogeneous nature of arterial obstructions raises the question of whether early and late outcomes (restenosis) of angioplasty are affected by the degree and direction of de novo atherosclerotic remodeling. This study was designed to assess the relationship between atherosclerotic remodeling and the degree and mechanism of restenosis after balloon angioplasty. Atherosclerosis was induced in 27 peripheral arteries of 18 Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed, with serial intravascular ultrasound and quantitative angiography before and after intervention and at 42 days' follow-up. We used the relative media-bounded area (MBA), defined as the MBA of the treated site divided by the MBA of the reference, before angioplasty as a measure of remodeling in de novo atherosclerosis and late MBA loss as a measure of remodeling after balloon angioplasty. Relative MBA before angioplasty was not correlated with angiographic and echographic acute gain after balloon angioplasty (r=.22, P=.28 and r=.14, P=.48) or with late lumen loss (r=-.05, P=.81 and r=.19, P=.33). No correlation was found between relative MBA and late MBA loss (r=.14 and P=.48). In the atherosclerotic Yucatan micropig, remodeling during de novo atherosclerosis has no relevance for acute gain and late lumen loss after balloon angioplasty. Both the direction and the extent of remodeling after balloon angioplasty are not related to the direction and extent of remodeling during de novo atherosclerosis.     

Treatment success with a mandibular advancement device is related to supine-dependent sleep apnea

OBJECTIVES: This study was performed to determine predictors of in-stent restenosis from a high volume, single-center practice. BACKGROUND: Intracoronary stents have been shown to reduce the restenosis rate as compared with balloon angioplasty, but in-stent restenosis continues to be an important clinical problem. METHODS: Between April 1993 and March 1997, 1,706 patients with 2,343 lesions were treated with a variety of intracoronary stents. The majority of stents were placed with high pressure balloon inflations and intravascular ultrasound (IVUS) guidance. Angiographic follow-up was obtained in 1,173 patients with 1,633 lesions (70%). Clinical, angiographic and IVUS variables were prospectively recorded and analyzed by univariate and multivariate models for the ability to predict the occurrence of in-stent restenosis defined as a diameter stenosis > or =50%. RESULTS: In-stent restenosis was angiographically documented in 282 patients with 409 lesions (25%). The restenosis group had a significantly longer total stent length, smaller reference lumen diameter, smaller final minimal lumen diameter (MLD) by angiography and smaller stent lumen cross-sectional area (CSA) by IVUS. In lesions where IVUS guidance was used, the restenosis rate was 24% as compared with 29% if IVUS was not used (p < 0.05). By multivariate logistic regression analysis, longer total stent length, smaller reference lumen diameter and smaller final MLD were strong predictors of in-stent restenosis. In lesions with IVUS guidance, IVUS stent lumen CSA was a better independent predictor than the angiographic measurements. CONCLUSIONS: Achieving an optimal stent lumen CSA by using IVUS guidance during the procedure and minimizing the total stent length may reduce in-stent restenosis.     

In vitro generation of an active calmodulin-independent phosphodiesterase from brain calmodulin-dependent phosphodiesterase (PDE1A2) by m-calpain

OBJECTIVES: We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials. BACKGROUND: The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance. METHODS: After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%). RESULTS: We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean +/- SD) (7.16 +/- 2.48 vs. 7.95 +/- 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 +/- 0.65 mm in Group A vs. 1.70 +/- 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 +/- 2.59 vs. 5.36 +/- 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis. CONCLUSIONS: A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial.     

Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis

BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of the long-term success of this procedure. The process of restenosis is similar to an accelerated form of atherosclerosis. Thus, therapeutic interventions that limit the progression and initiation of atherosclerosis may be beneficial in the treatment of restenosis. One such intervention is the antioxidant drug probucol, which has demonstrated benefit in animal models of atherosclerosis. METHODS AND RESULTS: Twenty-six female domestic swine were divided into three study groups (control, n = 9; low-dose probucol, n = 9; high-dose probucol, n = 8) before oversized balloon injury of the left anterior descending and left circumflex coronary arteries. Probucol (1 g/d, low-dose group; 2 g/d, high-dose group) was administered 2 days before balloon injury and was continued until the swine were killed 2 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), maximal intimal thickness (millimeters), and residual lumen (ratio of luminal to intimal plus luminal area). Treatment with high-dose probucol significantly reduced neointimal formation compared with control animals (decreases of 36% in intimal area, P = .007; 20% in maximal intimal thickness, P = NS; and an increase of 15% in residual lumen, P = .02). CONCLUSIONS: The major finding of this study is that the antioxidant drug probucol reduces neointimal formation after oversized balloon injury in a swine model of restenosis. This suggests that active oxygen species may play a role in restenosis.     

Serial investigation of balloon angioplasty induced changes in the superficial femoral artery using colour duplex ultrasonography

Percutaneous transluminal balloon angioplasty (PTA) of superficial femoral artery lesions is associated with similar initial success rates in coronary and iliac artery angioplasty but its application is limited by a much higher incidence of restenosis. To improve understanding of the trauma caused to the vessel by balloon angioplasty and the mechanisms contributing to the subsequent processes of healing and restenosis requires serial investigations of the treated arteries in vivo. This paper describes a prospective study using colour duplex ultrasonic imaging to assess arterial changes in 51 patients with atherosclerotic disease undergoing PTA of superficial femoral artery stenoses and occlusions. Each patient was scanned prior to angioplasty and at intervals up to 6 months post-angioplasty. On each scan, measurements were made of the overall vessel and lumen diameters at each site of angioplasty. These measurements indicate that angioplasty improves vessel patency mainly by stretching of the vessel wall, with compression and/or redistribution of the atherosclerotic plaque contributing less than 25% to the improvement of lumen diameter. Serial measurements after angioplasty show complex patterns of change at the angioplasty sites indicating that several mechanisms may be contributing to the processes of vessel healing and subsequent restenosis. Possible mechanisms which could explain the measured changes in overall vessel and lumen diameters are discussed.     

Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty: the FACT study. Fraxiparine Angioplastie Coronaire Transluminale

BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.     

Mechanisms of luminal enlargement and quantification of vessel wall trauma following balloon coronary angioplasty and directional atherectomy

OBJECTIVES: The purpose of this study was to assess the dual action of lumen enlargement and vessel wall damage following either balloon angioplasty or directional atherectomy, using intracoronary ultrasound, and angioscopy. BACKGROUND: Differences in the mechanisms of action of balloon angioplasty and directional atherectomy may have a significant bearing on the immediate outcome and the restenosis rate at 6 months. METHODS: A total of 36 patients were studied before and after either balloon angioplasty (n = 18) or directional atherectomy (n = 18). Ultrasound measurements included changes in lumen area, external elastic membrane area and plaque burden. In addition, the presence and extent of dissections were assessed to derive a damage score. Angioscopic assessment of the dilated or atherectomized stenotic lesions was translated into semi-quantitative dissection, thrombus and haemorrhage scores. RESULTS: Atherectomy patients had a larger angiographic vessel size compared with the angioplasty group (3.55 +/- 0.46 mm vs 3.00 +/- 0.64 mm, P < 0.05); however, minimal lumen diameter (1.18 +/- 0.96 mm vs 0.85 +/- 0.49 mm) and plaque burden (17.04 +/- 3.69 vs 15.23 +/- 4.92 mm2) measurements did not differ significantly. As a result of plaque reduction, atherectomy produced a larger increase in luminal area than the angioplasty group (5.80 +/- 1.78 mm2 vs 2.44 +/- 1.36 mm2, P < 0.0001). Lumen increase after angioplasty was the result of 'plaque compression' (50%) and wall stretching (50%). Additionally, in both groups there was indirect angioscopic evidence of thrombus 'microembolization' as an adjunctive mechanism of lumen enlargement. Angioscopy identified big flaps in six and small intimal flaps in 11 of the atherectomized patients as compared with five and 12 patients in the angioplasty group. Changes in thrombus score following both coronary interventions were identical (0.72 +/- 3.42 points atherectomy vs -0.38 +/- 3.27 points balloon angioplasty, ns). CONCLUSIONS: Lumen enlargement after directional atherectomy is mainly achieved by plaque removal (87%), whereas balloon dilation is the result of vessel wall stretching (50%) and plaque reduction (50%). Despite the fact that the luminal gain achieved by directional atherectomy is twice that achieved with balloon angioplasty, the extent of trauma induced by both techniques seems to be similar.     

Coronary artery restenosis after balloon angioplasty in humans is associated with circumferential coronary constriction

Therapies that inhibit intimal hyperplasia do not prevent restenosis after coronary artery balloon angioplasty, suggesting that additional mechanisms may be responsible for restenosis in humans. Using an intravascular ultrasound (Hewlett-Packard Sonos Intravascular Imaging System). 3.5F, 30-MHz (Boston Scientific) monorail imaging catheter, we studied 17 patients with clinical and angiographic restenosis at an average (mean +/- SD) of 7 +/- 6 months after balloon angioplasty (13 men age, 71 +/- 10 years; 12 left anterior descending coronary arteries, 4 right coronary arteries, and 1 left circumflex coronary artery) The lumen area (L.A), vessel wall area (VWA), and total cross-sectional area (CSA) within the external elastic lamina were measured at the restenosis site and at proximal and distal reference sites, which were defined as adjacent segments with the least amount of plaque. Consistent with coronary angiography findings, decreased LA at the restenotic site was detected in all 17 patients. The unique finding was that total CSA at the restenotic site was significantly decreased compared with both proximal and distal reference sites (10.1 +/- 2.4 versus 14.8 +/- 3.2 mm2 and 10.1 +/- 2.4 versus 13.8 +/- 3.1 mm2, respectively, P < .001), whereas VWA (intima plus media) was slightly increased at the angioplasty site compared with both proximal and distal reference sites (8.0 +/- 2.3 versus 7.6 +/- 2.3 mm2 and 8.0 +/- 2.3 versus 6.7 +/- 2.3 mm2, respectively, P = NS). Eighty-three percent of the loss in LA at the restenotic site was due to constriction of the total CSA, while the increase in VWA at the restenotic site accounted for only a 17% loss in LA. We then compared these results with the morphology of coronary artery segments in 14 patients without restenosis. These coronary artery segments had been previously treated with balloon angioplasty (7 +/- 5 months). Unlike that in restenotic lesions, the total CSA within the external elastic lamina at the sites of previous angioplasty was similar to that in distal and proximal reference sites (P = NS). Significant and consistent reduction in arterial CSA, with a minor increase in VWA, characterizes human coronary lesions that cause angiographic restenosis. These data suggest that in humans, "recoil" and/or vascular contraction with healing in response to balloon injury is a major contributor to restenosis after balloon angioplasty.     

Influence of destruction of retina-RPE complex on the proliferation of scleral chondrocytes in chicks

BACKGROUND: Restenosis remains the major limitation of coronary angioplasty. Coronary stents have reduced the incidence of restenosis in selected patients with relatively large vessels. No strategies to date have demonstrated a beneficial effect in vessels < 3.0 mm in diameter. We have shown in the MultiVitamins and Probucol (MVP) Trial that probucol, a potent antioxidant, reduces restenosis after balloon angioplasty. The purpose of this study was to determine whether the benefit of probucol therapy is maintained in the subgroup of patients with smaller coronary vessels. METHODS AND RESULTS: We studied a subgroup of 189 patients included in the MVP trial who underwent successful balloon angioplasty of at least one coronary segment with a reference diameter < 3.0 mm. One month before angioplasty, patients were randomly assigned to one of four treatments: placebo, probucol (500 mg), multivitamins (beta-carotene 30000 IU, vitamin C 500 mg, and vitamin E 700 IU), or probucol plus multivitamins twice daily. The treatment was maintained until follow-up angiography was performed at 6 months. The mean reference diameter of this study population was 2.49+/-0.34 mm. Lumen loss was 0.12+/-0.34 mm for probucol, 0.25+/-0.43 mm for the combined treatment, 0.35+/-0.56 mm for vitamins, and 0.38+/-0.51 mm for placebo (P=.005 for probucol). Restenosis rates per segment were 20.0% for probucol, 28.6% for the combined treatment, 45.1% for vitamins, and 37.3% for placebo (P=.006 for probucol). CONCLUSIONS: Probucol reduces lumen loss and restenosis rate after balloon angioplasty in small coronary arteries.     

Effect of the antioxidant Nicanartine on the proliferative and inflammatory response after experimental balloon angioplasty

BACKGROUND: Antioxidant treatment seems to reduce the development of restenosis after percutaneous transluminal angioplasty. In this study, the effect of Nicanartine, a new antioxidant drug with both antiproliferative and lipid-lowering properties, on the proliferative and inflammatory response after balloon angioplasty was investigated in a rabbit model of restenosis. METHODS: To induce pre-interventional plaques in the common carotid artery of 48 New Zealand White rabbits, electrostimulation was carried out for 28 days. After a break of 7 days, balloon angioplasty was performed in 36 animals, of which 18 received Nicanartine at a dose of 120 mg/kg body weight; the other 18 served as a control group. The vessels were excised by day 7 and 28 after balloon angioplasty and examined for intimal plaque size, macrophage content and proliferative activity. Bromodeoxyuridine labeling was used to determine proliferating cells in the dilated segment; macrophages were detected using the RAM-11 antibody. RESULTS: In the Nicanartine-treated group, immunohistological quantification 7 days after intervention showed a statistically significant (P< 0.05) reduction of both cells undergoing DNA synthesis (1.6+/-1.4% versus 3.7+/-2.2%) and intimal macrophages (0.7+/-1.2% versus 1.3+/-0.6%). Twenty-eight days after balloon angioplasty, proliferative activity in both groups was decreased to a level comparable to the non-dilated control groups. A clear trend towards smaller plaques could be seen in the Nicanartine group (0.146+/-0.077 mm2 versus 0.255+/-0.174 mm2). Total cholesterol levels did not differ significantly between the groups. CONCLUSION: Under treatment with Nicanartine a clear reduction in the proliferative and inflammatory response after balloon angioplasty was observed. Antioxidant treatment, especially with compounds having antiproliferative and lipid-lowering properties, appears to be an effective secondary preventive strategy after interventional treatment in patients with coronary artery disease.     

The placebo in modern medicine

PURPOSE: To report the results of balloon angioplasty in recurrent carotid occlusive disease and evaluate the potential for stent implantation. METHODS AND RESULTS: Between April 1991 and September 1995, 15 patients with carotid restenosis underwent 17 endoluminal procedures in 3 common carotid and 14 internal carotid arteries. Two postdilation complications (dissection and acute occlusion) required prompt stenting; one common carotid artery was stented for postdilation residual stenosis. One recurrent lesion was also stented 6 months after initial angioplasty. One stroke, 1 silent cerebral infarction, and 3 transient ischemic attacks occurred in the balloon angioplasty patients (33% neurological complication rate). The common carotid stent patient died 3 days postoperatively due to hyperperfusion syndrome. Long-term follow-up in two stent patients showed no restenosis at 18 and 48 months, respectively. The 11 balloon angioplasty patients likewise have not demonstrated restenosis. CONCLUSIONS: Balloon angioplasty alone appears too risky for treating recurrent carotid disease. Stents may offer a safer alternative, particularly when implanted primarily.     

The relation between multiple sleep latency test findings and the frequency of apneic events in REM and non-REM sleep

OBJECTIVES: The purpose of this prospective study was to evaluate the immediate results and the 6-month angiographic recurrent restenosis rate after balloon angioplasty for in-stent restenosis. BACKGROUND: Despite excellent immediate and mid-term results, 20% to 30% of patients with coronary stent implantation will present an angiographic restenosis and may require additional treatment. The optimal treatment for in-stent restenosis is still unclear. METHODS: Quantitative coronary angiography (QCA) analyses were performed before and after stent implantation, before and after balloon angioplasty for in-stent restenosis and on a 6-month systematic coronary angiogram to assess the recurrent angiographic restenosis rate. RESULTS: Balloon angioplasty was performed in 52 patients presenting in-stent restenosis. In-stent restenosis was either diffuse (> or =10 mm) inside the stent (71%) or focal (29%). Mean stent length was 16+/-7 mm. Balloon diameter of 2.98+/-0.37 mm and maximal inflation pressure of 10+/-3 atm were used for balloon angioplasty. Angiographic success rate was 100% without any complication. Acute gain was lower after balloon angioplasty for in-stent restenosis than after stent implantation: 1.19+/-0.60 mm vs. 1.75+/-0.68 mm (p=0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no patient died. Eighteen patients (35%) had repeat target vessel revascularization. Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when in-stent restenosis was diffuse: 63% vs. 31% when focal, p=0.046. CONCLUSIONS: Although balloon angioplasty for in-stent restenosis can be safely and successfully performed, it leads to less immediate stenosis improvement than at time of stent implantation and carries a high recurrent angiographic restenosis rate at 6 months, in particular in diffuse in-stent restenosis lesions.     

An explanation for discrepancy between angiographic and intravascular ultrasound measurements after percutaneous transluminal coronary angioplasty

OBJECTIVES: This study attempted to determine why there is a discrepancy between angiographic and intravascular ultrasound measurements after coronary balloon angioplasty. BACKGROUND: Previous studies have shown a poor correlation between angiographic and intravascular ultrasound measurements after percutaneous coronary balloon angioplasty. METHODS: After successful balloon angioplasty, 91 lesions in 84 patients were studied by intravascular ultrasound. Plaque morphology on intravascular ultrasound was classified as demonstrating a superficial injury if there was either no fracture or only a small tear that did not extend to the media versus a deep injury defined as the presence of a plaque fracture that reached the media. Measurements of minimal lumen diameter were compared between angiography and intravascular ultrasound. RESULTS: On ultrasound imaging, a superficial injury pattern was observed in 44 lesions, whereas a deep injury was seen in 47 lesions. There were no statistical differences at baseline in patient or lesion characteristics. In the superficial injury group there was a significant correlation between angiography and intravascular ultrasound for minimal lumen diameter (r = 0.67) and lumen cross-sectional area (r = 0.69). In the deep injury group there was a poor correlation for minimal lumen diameter (r = 0.05) and lumen cross-sectional area (r = 0.28). After balloon angioplasty, the angiographic appearance showed a normal contour in 34%, the presence of dissection in 38% or a hazy appearance in 23%. On ultrasound imaging after angioplasty, the superficial injury group comprised 65% of lesions with a normal angiographic appearance and 67% of lesions with a hazy appearance, whereas 77% of lesions with an angiographic diagnosis of dissection were in the deep injury group by ultrasound (p = 0.0005). CONCLUSIONS: These observations suggest that the discrepancies between angiographic and ultrasound measurements are due to differences in plaque morphology created by balloon dilation. Superficial injuries demonstrate similar results by angiography or ultrasound, whereas a deep injury to the plaque produces a difference in measurements between angiography and ultrasound. When angiography reveals a dissection, there is a high probability that intravascular ultrasound will demonstrate a plaque fracture extending to the media.     

Development of an avian model for restenosis

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.     

Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels

BACKGROUND: Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients. METHODS AND RESULTS: We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P=.0002) owing to both a greater late loss (0.79+/-0.70 versus 0.41+/-0.61 mm, respectively; P<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively; P<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77+/-0.65 versus 0.79+/-0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients. CONCLUSIONS: Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.     

Bimodal distribution of angiographic measures of restenosis six months after coronary stent placement

BACKGROUND: Restenosis has been perceived as the tail end of a normal distribution of the response of the vessel to the intervention. However, recent studies have described a bimodal distribution for de novo lesions after percutaneous transluminal coronary angioplasty. This finding suggests that some lesions may be more susceptible for restenosis. Whether this holds true for a wider spectrum of lesions undergoing stent placement is not yet known. The present study analyzes the frequency distribution of angiographic indexes of restenosis 6 months after coronary stent implantation. METHODS AND RESULTS: Quantitative angiographic evaluation was performed in 1084 lesions of 1084 patients before, immediately after, and 6 months after successful Palmaz-Schatz stent placement; this represented 80.4% of patients eligible for follow-up angiography. Principal end points of the analysis were angiographic indexes of restenosis at 6 months. Twenty-two lesions that became totally occluded at follow-up were excluded from most parts of the analysis. Diameter stenosis, minimal luminal diameter (MLD), and lumen loss at 6 months did not follow a normal pattern; the bimodal pattern was demonstrated through deconvolution that yielded two separate normal components delineating two lesion populations, which developed distinctively different degrees of lumen renarrowing. The first and larger subgroup of lesions, which was less prone to restenosis, was centered around a mean value of 27% for diameter stenosis and 2.19 mm for MLD, whereas the second subgroup, with a greater tendency for restenosis, was situated around a mean value of 68% for diameter stenosis and 0.76 mm for MLD. The intersection point between the two theoretical normal distribution components was 53.5% for diameter stenosis and 1.09 mm for MLD at follow-up. CONCLUSIONS: Frequency-distribution curves of angiographic indexes of restenosis after coronary stent placement have a bimodal pattern, suggesting the existence of two distinct populations with different propensity to restenosis. These findings may encourage future efforts for the timely identification of the subset with a higher risk as the target of specific antirestenotic strategies.     

Dietary and non-dietary factors associated with iron status in a cohort of Danish adults followed for six years

PURPOSE: Suboptimal distal coronary flow reserve after successful balloon angioplasty has been attributed to angiographically unrecognized inadequate lumen expansion, and adjunct coronary stenting has been shown to improve coronary flow reserve. The aim of this study was to investigate whether myocardial fractional flow reserve (FFRmyo) would increase further after coronary stenting compared with balloon angioplasty alone in the same patient group. METHODS: FFRmyo and quantitative coronary angiography were obtained before and after pre-stent balloon dilation, and again after stent placement in 11 patients (7 left anterior descending artery, 3 right coronary artery and 1 left circumflex artery). FFRmyo was calculated as the ratio of Pd/Pa during intracoronary adenosine 5'-triphosphate (50 micrograms and 20 micrograms in the left and right coronary arteries, respectively)-induced maximum hyperemia, where Pd represents mean distal coronary pressure measured by a 2.1 Fr infusion catheter and Pa represents mean aortic pressure measured by the guiding catheter. RESULTS: Percent diameter stenosis significantly decreased after balloon angioplasty (74% +/- 15% vs 37% +/- 17%, p < 0.001), and decreased further after stent placement (18% +/- 10%, p < 0.001 vs baseline and balloon angioplasty). FFRmyo after coronary stenting (0.85 +/- 0.09) was significantly higher than that at baseline (0.51 +/- 0.16, p < 0.001) and after balloon angioplasty (0.77 +/- 0.11, p < 0.05). There was a significant correlation between angiographic variables and FFRmyo. The increase in lumen dimensions after coronary stenting was followed by a further significant improvement of FFRmyo. CONCLUSION: These results suggest that coronary stenting may provide a more favorable functional status and lumen geometry of residual coronary stenosis compared with balloon angioplasty alone.     

Radiofrequency thermal balloon coronary angioplasty: a new device for successful percutaneous transluminal coronary angioplasty

OBJECTIVES: The purpose of this study was to evaluate the effects of thermal balloon percutaneous transluminal coronary angioplasty using radiofrequency energy in the treatment of patients with failed coronary angioplasty and complex lesions. In addition, we evaluated restenosis after radiofrequency thermal balloon applications. BACKGROUND: The efficacy of coronary angioplasty is limited by the relatively low success rate in complex lesions and the high frequency of restenosis. Few reports have studied the combined effects of pressure and laser thermal energy. This study describes a new device for coronary angioplasty using radiofrequency thermal energy. METHODS: Thirty-two patients with failed conventional coronary angioplasty or complex lesions were treated with radiofrequency thermal balloon coronary angioplasty. Radiofrequency energy was delivered up to 11 times in exposures ranging from 30 to 60 s in duration. This combined effect allowed the vascular wall to be heated to temperatures ranging from 60 to 70 degrees C. Follow-up coronary angiography was performed, on average, 6 months after the procedure. RESULTS: Successful radiofrequency coronary angioplasty was achieved in 28 (82%) of 34 lesions. There was one abrupt coronary artery occlusion (3%) and no death, perforation or dissection. Angiographic restenosis occurred in 14 (56%) of 25 lesions. CONCLUSIONS: In patients with failed coronary angioplasty and difficult complex lesions, radiofrequency coronary angioplasty could potentially improve angioplasty success rates and may have important implications for bailout cases with abrupt occlusion. However, restenosis remains a significant problem.     

Percutaneous transluminal angioplasty in atherosclerosis

Percutaneous transluminal balloon angioplasty has achieved a dominant role in the interventional treatments of atherosclerotic peripheral, renal, and coronary artery disease. Improved operator's technique and equipment design have increased the primary success rate. Despite improved success rate and safety, acute closure, late restenosis and difficulty in treating chronic total occlusions or diffuse lesions remain as serious limitations of this procedure. To overcome these limitations of balloon angioplasty, new devices such as stenting, atherectomy or laser ablation have been developed. Although there are many problems for each device, these techniques appear to reduce the limitations in angioplasty.