The role of stent-grafts for prevention and treatment of restenosis.

Restenosis rates in the superficial femoral artery remain high in patients treated with balloon angioplasty or bare metal stents. Stent-grafts represent an alternative endovascular treatment modality for these patients. In the US, the only FDA-approved stent-graft for femoral use is the Viabahn endoprosthesis (W.L. Gore, Flagstaff, AZ). The Viabahn is constructed of nitinol and ePTFE and has a proprietary heparin bioactive surface. Stent-grafts have the potential to reduce restenosis by impeding intimal hyperplasia and reducing tissue in-growth; however, the problem of edge restenosis has not been eliminated. Graft thrombosis remains an important mode of stent-graft failure. The Viabahn has been shown in observational studies and randomized trials to be an effective and safe treatment strategy compared to bare self-expanding stents and surgical prosthetic bypass grafts. Patient and appropriate lesion selection remain important in achieving long term patency. In this paper, we review the data surrounding the use of stent-grafts in the SFA to prevent and treat restenosis. Important technical considerations specific to the use of the Viabahn are also discussed.

Excimer laser assisted angioplasty for complex infrainguinal peripheral artery disease: a 2008 update.

Conventional percutaneous transluminal angioplasty (PTA) for complex or long segment infrainguinal occlusive arterial disease is limited by elastic recoil, dissection and restenosis, with high rates of intermediate and long term restenosis . Debulking with excimer laser has been advocated as a useful adjunctive strategy to improve procedural success and long term patency. This paper reviews the technological development of excimer laser, the studies supporting its use in infrainguinal arterial disease, effective and safe lasing techniques, its advantages, limitations and disadvantages. Case examples will be presented to illustrate its use in infrainguinal arterial disease. Although randomized controlled trials are lacking, existing registry and case series studies suggest efficacy of the excimer laser-assisted PTA for complex infrainguinal arterial disease, including patients with critical limb ischemia.

Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model.

OBJECTIVES: This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. BACKGROUND: Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. METHODS: Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. RESULTS: The area of thrombus was minimal at 24 h ([mean +/- SE] 0.44 +/- 0.12 mm2). Neointimal area at 7 days (0.72 +/- 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 +/- 0.39 mm2) and 28 days (3.30 +/- 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 +/- 3.5% at 7 days compared with 9.6 +/- 1.3% by 14 days (p = 0.0247) and declined to 1.1 +/- 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days). CONCLUSIONS: Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.

Coronary stenting with a novel stainless steel balloon-expandable stent: determinants of neointimal formation and changes in arterial geometry after placement in an atherosclerotic model.

OBJECTIVES: This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis. BACKGROUND: The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized. METHODS: We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement. RESULTS: Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 +/- 0.09 mm (reference diameter 2.87 +/- 0.06 mm, mean +/- SE) and increased to 2.82 +/- 0.05 mm (p < 0.001) after stent placement. The balloon-inflated stent diameter was 2.98 +/- 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 +/- 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 +/- 0.01 vs. 0.27 +/- 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 +/- 0.27 vs. 2.68 +/- 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 +/- 0.34 mm2) than nonstented atherosclerotic vessels (0.44 +/- 0.28 mm2, p = 0.033). CONCLUSIONS: Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.

Automated calcium burden measurement in internal carotid artery plaque with CT: a hierarchical adaptive approach.

AIM: Calcium burden measurement in internal carotid artery (ICA) plaque could play an important role in assessing stroke risk and stenosis quantification in the ICA. We propose an automatic method for labelling calcified plaques in ICA in CT images. METHODS: Our approach builds upon the mean shift paradigm via an adaptive thresholding strategy. The data consists of single CT slices from 75 patients, with variety of plaque sizes and number of calcium regions. The manual measurements were carried out by a neuroradiologist for benchmarking. The calcium burden was measured as the area of the labelled plaque. Various metrics were employed to compare manual and automated measurements including correlation coefficient (CC), dice similarity (DS), Jacard Index (JI), polyline distance metric (PDM) and precision of merit (PoM). RESULTS: We found that our automated method of calcium area characterization performed accurately compared to manual measurements with CC=0.978, and PoM=0.915. The PDM, DS, and JI, also indicate a good performance with a mean DS=0.85 (SD=0.085), a mean JI=0.747 (SD=0.12), and a mean PDM=0.195 (SD=0.177). CONCLUSION: The proposed approach for calcium burden measurement, yields reasonably accurate labelling of calcified plaque when benchmarked against manual measurements. The approach is independent of the number and size of calcium regions, and the prototype design shows encouraging results to be adaptable to clinical practice.

Experimental results with endovascular irradiation via a radioactive stent.

PURPOSE: The objective of this article is to describe the methods used to manufacture a radioactive stent and to review the experimental data on this therapy designed to improve arterial patency rates after stent placement. MATERIALS AND METHODS: Surface activation in a cyclotron and ion implantation techniques are used to render commercially available vascular stents radioactive. beta-Particle-emitting stents, most commonly 32P, were employed because of their short half-life (14.3 days) and limited range of tissue penetration (3-4 mm). The function and vascular response to these 32P radioactive stents with varying activities (range 0.14-23 microCi) was evaluated in several animal models of arterial injury and restenosis. RESULTS: In porcine iliac arteries, beta-particle-emitting stents with an initial activity of 0.14 microCi reduced neointimal formation 37% at 28 days after implant. On histology, the neointima consisted of smooth muscle cells and a proteoglycan-rich matrix. Scanning electron microscopy demonstrated complete endothelialization of the stent. beta-Particle-emitting stents with an initial activity of 3-23 microCi inhibited neointimal smooth muscle cell proliferation at 28 days in a porcine coronary restenosis model. The neointima within these high-activity stents consisted of fibrin, erythrocytes, and only rare smooth muscle cells. Studies with 1-year follow-up after implantation of a radioactive stent with a composition of gamma- and beta-particle-emitting radionuclides 55,56,57Co, 52Mg, and 55Fe and an initial activity of 17.5 microCi demonstrated almost complete inhibition of neointimal proliferation in a rabbit model. CONCLUSION: Endovascular irradiation delivered via a radioactive stent reduces neointimal formation and improves luminal patency without increasing the risk for stent thrombosis in experimental models of restenosis. The optimal radiation dose is unknown. At stent activities >3 microCi of 32P, the inhibition of neointimal formation is due to direct radiation affects on proliferating smooth muscle cells. At ultra-low activities (0.14 microCi), beta-particle irradiation reduces neointimal formation possibly by impairing cell proliferation or migration. This novel therapy may have a significant impact on preventing stent restenosis, and requires further investigation.

The beta-particle-emitting radioisotope stent (isostent): animal studies and planned clinical trials.

Radiation delivered by intravascular stent is an appealing approach to prevent neointimal hyperplasia, since it nonselectively kills dividing cells. In particular, beta-particle-emitting radioisotope stents may prove to be an ideal means of local irradiation in that 95% of the dose is delivered within 4 mm of the stent edge and the dose drops off rapidly to < 1/1,000 of the original dose at 5 months postimplantation. In the in vitro smooth muscle cell model, one can observe a zone of growth inhibition around radioactive stent wires that averages about 6 mm at very-low-activity levels (0.006 microCi/cm of wire). In vivo studies in animal models, including porcine iliac and coronary arteries and rabbit iliac arteries, have shown the effectiveness of radioisotope stents in inhibiting neointimal proliferation. Proliferating endothelial cells appear to be relatively radioresistant. A computer model was employed to look at the radiation dose delivered as a function of distance from the stent. With very-low-activity stents, presumably, DNA of the smooth muscle cells is damaged as they migrate through the "electron fence" on the way to the neolumen, diminishing the population of myofibroblasts and reducing hyperplasia. Catheter-based radiation therapies may disable these cells before they migrate, although such an approach may not inhibit early recoil or late contraction. Based on the characteristics of beta emissions (i.e., rapid drop-off, minimal leaching), radioisotope stents containing phosphorus-32 appear to be safe. A randomized triple-blind clinical trial is planned to assess restenosis at 6 months in native coronary arteries treated with radioisotope stents.

Lipid-lowering therapy after coronary revascularization: the interventional cardiologist's perspective.

Despite the success of coronary interventions in the treatment of stenosis due to coronary atherosclerosis, it behooves cardiologists to treat the underlying disease by decreasing patients' cholesterol levels. Intravascular ultrasound has made it possible to detect plaque accumulation not visible on angiography. Although advanced lesions that are fibrous and calcific can be treated with atherectomy and lasers, it is the soft, lipid-laden plaque that is particularly vulnerable to rupture and leads to coronary events. Therefore, attention must also focus on decreasing atherosclerotic progression in patients who have undergone coronary interventions. Studies have clearly shown the value of cholesterol reduction in decreasing coronary events. However, a review of cardiologists' practices shows that more aggressive lipid-lowering therapy is needed. One way to achieve this goal is to treat and monitor patients who have undergone revascularization procedures and to encourage patients to become more involved in their own care.

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.

Angiographic and procedural outcome after coronary angioplasty in high-risk subsets using a decremental diameter (tapered) balloon catheter. Tapered Balloon Registry Investigators.

The angiographic and clinical outcomes of 115 patients (129 lesions) treated at 11 clinical centers using a decremental diameter (tapered) balloon catheter were evaluated. The presence of marked tapering of the reference vessel, lesion location involving a bifurcation or anastomosis of a saphenous vein graft, or total coronary occlusion where estimation of the distal vessel size was difficult were indications for this device. The tapered balloon was used as the initial dilatation device in 62 patients (73 narrowings), and as a secondary device in 53 patients (56 narrowings). Lesions selected for tapered balloon angioplasty were generally complex (95% had > or = 1 and 60% had > or = 2 adverse morphologic features). Vessel diameters were larger in the proximal reference segments (3.07 +/- 0.52 mm) than in distal ones (2.48 +/- 0.45 mm) (p<0.001). After tapered balloon angioplasty, the minimal lumen diameter increased from 0.85 +/- 0.34 mm to 2.13 +/- 0.50 mm (p<0.001), and the percent diameter stenosis decreased from 69 +/- 12% to 24 +/- 12% (p<0.001). Coronary dissections occurred in 20% of lesions; they were severe in 4% (National Heart, Lung, and Blood Institute grade C to F). Abrupt closure occurred in 4.3% of patients (2.6% immediate; 1.7% delayed). Procedural success was obtained in 110 patients (96%); major complications (in-hospital death, myocardial infarction, or emergency coronary bypass surgery) occurred in 3 patients (2.7%). Coronary angioplasty using the tapered balloon catheter appears to be a safe and effective technique for the treatment of complex lesion subsets, particularly those involving coronary arteries with marked segmental tapering.

Comparative early and nine-month results of rotational atherectomy, stents, and the combination of both for calcified lesions in large coronary arteries.

The aim of this study was to determine the preferred treatment modality for calcified lesions in large (> or = 3 mm) coronary arteries, resulting in the largest lumen dimensions and the most favorable late clinical responses. Three hundred six lesions in 306 patients (223 men, mean age 66 +/- 11 years) were treated with either rotational atherectomy plus adjunct balloon angioplasty (n = 147), Palmaz-Schatz stents (n = 103), or a combination of rotational atherectomy plus adjunct Palmaz-Schatz stents (n = 56). The procedural success rate was 98.0% to 98.6% for each treatment modality. Minimal lumen diameter (MLD) before therapy was similar for all therapies. Final MLD after combination of rotational atherectomy plus Palmaz-Schatz stents was larger than after stent therapy or rotational atherectomy plus balloon angioplasty (3.21 +/- 0.49 mm, 2.88 +/- 0.51 mm, and 2.29 +/- 0.55 mm, respectively, p <0.0001). Correspondingly, final percent diameter stenosis was lowest after the combination of rotational atherectomy plus stent therapy, and significantly higher for stents or rotational atherectomy plus balloon angioplasty (4.2 +/- 15.3%, 14.1 +/- 13.3%, and 26.7% +/- 16.9%, respectively, p <0.0001). Event-free survival at 9 months was higher for patients treated with the combination of rotational atherectomy plus stents than either stent therapy or rotational atherectomy alone (85%, 77%, and 67%, respectively, log-rank p = 0.0633). The only significant independent predictor of an event during the 9-month follow-up period was the MLD after intervention (odds ratio 0.495, 95% confidence interval 0.308 to 0.796, p = 0.0037). We conclude that preatheroablation using rotational atherectomy, followed by adjunct stent placement for calcified lesions in large arteries, is associated with infrequent complications, the largest acute angiographic results, and the most favorable late clinical event rates.

Treatment of symptomatic cervical carotid dissections with endovascular stents.

OBJECTIVE: Symptomatic dissections of the cervical carotid artery (CCA) can be spontaneous or secondary to trauma and may be associated with pseudoaneurysms. Surgical treatment is often difficult or unavailable. We report the successful use of endovascular stents in the treatment of symptomatic dissection of the CCA. METHODS: Five consecutive patients with symptomatic CCA dissection were seen at our institution. There were four female patients and one male patient, ranging in age from 19 to 56 years. One dissection was spontaneous. The others were secondary to a gunshot wound (one patient), blunt neck trauma (two patients), and endovascular treatment of atherosclerotic carotid bifurcation disease (one patient). Balloon-expandable and self-expanding stents were placed via a transfemoral approach. RESULTS: Success in restoring the carotid lumen with two to five stents in each patient was angiographically demonstrated. There were no procedure-related complications. All patients experienced significant clinical improvement within the first 24 hours and complete long-term recovery. CONCLUSION: Symptomatic dissections of the CCA can be successfully treated by using endovascular stents.

Intra-arterial reteplase for the treatment of acute limb ischemia.

The removal of urokinase from the market has created a dilemma for interventionists and vascular surgeons treating patients with acute limb threatening ischemia due to arterial thrombosis or embolization. Reteplase is a newer, fibrin-specific thrombolytic agent with properties that make it an attractive alternative to urokinase. We report two cases of successful treatment of acute, limb threatening ischemia with intra-arterial Reteplase therapy.

Excimer laser assisted angioplasty for the treatment of critical limb ischemia.

Two decades after the clinical introduction of percutaneous transluminal angioplasty (PTA), controversy still exists about the role of PTA for the treatment of occlusive disease in the femoropopliteal and infragenicular arteries. For the patient with critical limb ischemia (CLI), where diffuse disease and long occlusions are the rule, the results with PTA have not been optimal. Surgical revascularization has long been considered the gold standard for this patient population, but this procedure is associated with significant morbidity and mortality and up to 37% of patients may be poor surgical candidates. With advances in laser catheter design and refinement of recanalization techniques, improved results have been seen with laser assisted angioplasty of complex peripheral arterial disease. There has been renewed interest in excimer laser angioplasty for the treatment of patients with long total occlusions and diffuse disease who otherwise would have limited options for treatment. Excimer laser assisted angioplasty has been shown to be a successful approach to the treatment of long occlusions in the superficial femoral artery. Data from the recently completed Laser Angioplasty for Critical Limb Ischemia Phase 2 Trial (LACI) suggest that this is a viable treatment strategy for patients with CLI who are otherwise not good candidates for bypass surgery.

Swallow syncope associated with complete atrioventricular block: a case report and review of the literature.

Swallow or deglutition syncope is a very unusual but treatable disorder. A 44-year-old male presented with multiple, recurrent episodes of complete atrioventricular block associated with swallowing. Over a 24-hour period, 92 episodes of complete atrioventricular block occurring with meals were recorded by Holter monitoring. Evaluation did not demonstrate any underlying esophageal or cardiac disease. A trial of anticholinergic medications was unsuccessful. The patient's symptoms resolved following placement of a demand cardiac pacemaker. This is a rare but potentially lethal disorder that can be successfully treated if recognized. Physicians should be alerted to symptoms of lightheadedness or syncope during meals.

Femoropopliteal in-stent restenosis: current treatment strategies.

Nitinol self-expanding stents are increasingly used to treat symptomatic peripheral arterial disease. Despite reduction in procedural complications and rates of stent fracture, femoropopliteal in-stent restenosis (FP-ISR) remains a common and important clinical problem. Due to heterogenous patient and angiographic characteristics, treatment of FP-ISR continues to evolve. Multiple modalities have been evaluated including standard balloon angioplasty, cutting or scoring balloon angioplasty, repeat stenting (nitinol stent vs. stent-graft vs. drug eluting stent), excisional or laser atherectomy, drug coated balloon angioplasty, and atherectomy followed by drug coated balloon angioplasty. This review highlights the clinical evidence for the currently available modalities in the treatment of FP-ISR. Future studies should utilize uniform classification schemes and assess similar outcomes to help determine the optimal approach for endovascular treatment of FP-ISR.

The management of acute limb ischemia: techniques for dealing with thrombus.

Acute limb ischemia (ALI) has long been a major clinical problem, producing significant risks for limb loss and death. It is most commonly caused by arterial thrombosis in the setting of underlying atherosclerotic peripheral vascular disease or by arterial embolism, usually of cardiac origin. Over the past several decades, preferred treatment options for ALI have alternated between medical and surgical approaches. More recently, direct intra-arterial thrombolysis became the standard of care after several randomized trials demonstrated the benefit of this approach as compared with acute surgical intervention. Despite all of the experience with direct intra-arterial thrombolysis for the treatment of ALI, the optimal thrombolytic approach not been clearly established. Current investigation is directed at identifying the ideal thrombolytic agent for this purpose and the appropriate dosing regimen. In addition, there is interest in the newer mechanical thrombectomy devices and the use of platelet glycoprotein IIb/IIIa inhibitors to speed the time to reperfusion of the acutely ischemic limb.

Side-branch occlusion with directional coronary atherectomy: incidence and risk factors.

Side-branch occlusion is a recognized complication of directional coronary atherectomy (DCA). To evaluate the incidence, risk factors, and clinical outcome of side-branch compromise, we analyzed our first 100 consecutive atherectomies of native coronary arteries. Seventy-eight patients had 122 side branches at risk, 21 (17%) of which demonstrated compromised flow after DCA. Origin of the side branch from the culprit atheroma and preexisting side-branch ostial stenosis were highly predictive of this complication in 20 of 55 (p < 0.05) and 14 of 31 (p < 0.05) lesions, respectively. There was one non-Q-wave myocardial infarction, no emergency surgeries, and no deaths. In conclusion, side-branch loss after DCA occurs with a frequency similar to balloon angioplasty and was well tolerated in our patient population. Side branches that originate directly from culprit lesions or that have significant ostial narrowing have a higher incidence of this complication.