Benjamin Wiesinger

Sirolimus-Eluting Stents for the Treatment of Obstructive Superficial Femoral Artery Disease Six-Month Results

Background—Stent implantation for obstructive femoropopliteal artery disease has been associated with poor long-term outcomes. This study evaluated the effectiveness of shape memory alloy recoverable technology (SMART) nitinol self-expanding stents coated with a polymer impregnated with sirolimus (rapamycin) versus uncoated SMART stents in superficial femoral artery obstructions. Methods and Results—Thirty-six patients were recruited for this double-blind, randomized, prospective trial. All patients had chronic limb ischemia and femoral artery occlusions (57%) or stenoses (average lesion length, 85±57 mm). Patients were eligible for randomization after successful guidewire passage across the lesion. Eighteen patients received sirolimus-eluting SMART stents and 18 patients received uncoated SMART stents. The primary end point of the study was the in-stent mean percent diameter stenosis, as measured by quantitative angiography at 6 months. The in-stent mean percent diameter stenosis was 22.6% in the sirolimus-eluting stent group versus 30.9% in the uncoated stent group (P =0.294). The in-stent mean lumen diameter was significantly larger in the sirolimus-eluting stent group (4.95 mm versus 4.31 mm in the uncoated stent group;P =0.047). No serious adverse events (death or prolonged hospitalization) were reported. Conclusions—The use of sirolimus-eluting SMART stents for superficial femoral artery occlusion is feasible, with a trend toward reducing late loss compared with uncoated stents. The coated stent also proved to be safe and was not associated with any serious adverse events.

Drug-Eluting and Bare Nitinol Stents for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery: Long-Term Results from the SIROCCO Trial

Purpose: To review clinical outcomes of patients with chronic limb ischemia and TASC type C lesions treated with sirolimus-eluting versus bare SMART nitinol self-expanding stents. Methods: Data were obtained from a randomized, multicenter, double-blinded study conducted in 2 phases. All 93 patients had chronic limb ischemia and superficial femoral artery (SFA) occlusions or stenoses (average lesion length 8.3 cm). In total, 47 patients (31 men; mean age 66.3±9.1 years, range 50–84) received the sirolimus-eluting SMART stent and 46 patients (36 men; mean age 65.9 ± 10.8 years, range 38–83) received a bare SMART nitinol stent. Both groups were followed for a mean 24 months. Results: Both the sirolimus-eluting and the bare SMART stents were effective in revascularizing the diseased SFA and in sustaining freedom from restenosis. For both types of stents, improvements in ankle-brachial indices (ABI) and symptoms of claudication were maintained over 24 months (median 24-month ABI 0.96 for the sirolimus group versus 0.87 for the bare stent group, p>0.05). At 24 months, the restenosis rate in the sirolimus group was 22.9% versus 21.1% in the bare stent group (p>0.05). The cumulative in-stent restenosis rates according to duplex ultrasound were 4.7%, 9.0%, 15.6%, and 21.9%, respectively, at 6, 9, 18, and 24 months; the rates did not differ significantly between the treatment groups. The TLR rate for the sirolimus group was 6% and for the bare stent group 13%; the TVR rates were somewhat higher: 13% and 22%, respectively. Mortality rates did not differ significantly between the groups. Conclusion: These data demonstrate that the sirolimus-eluting and the bare SMART stent are effective, safe, and free from restenosis in a majority of patients for up to 24 months. Because the restenosis rate in the bare stent group is unexpectedly low, no significant difference could be found between the sirolimus-eluting and the bare SMART stents.

Sirolimus-Eluting versus Bare Nitinol Stent for Obstructive Superficial Femoral Artery Disease: The SIROCCO II Trial

PURPOSE To investigate further the safety and efficacy of the sirolimus-eluting S. M.A.R.T. Nitinol Self-expanding Stent by comparison with a bare stent in superficial femoral artery (SFA) obstructions. MATERIALS AND METHODS This randomized, double-blind study involved 57 patients (29 in the sirolimus-eluting stent group and 28 in the bare stent group) with chronic limb ischemia and SFA occlusions (66.7%) or stenoses (average lesion length, 81.5 mm +/- 41.2). Stent implantation followed standard interventional techniques and a maximum of two stents could be implanted. The primary endpoint was the in-stent mean lumen diameter at 6 months as determined by quantitative angiography. RESULTS Both stent types were effective in revascularizing the diseased SFA and allowing sustained patency for at least 6 months. There was no statistically significant difference between treatment groups in the in-stent mean lumen diameter at 6 months (4.94 mm +/- 0.69 and 4.76 mm +/- 0.54 mm for sirolimus-eluting and bare stent groups, respectively; P = .31). Although the diameter of the target lesion tended to be larger and percent stenosis tended to be lower with the sirolimus-eluting stent, there were no statistically significant differences between treatments in terms of any of the variables. The mean late loss values were 0.38 mm +/- 0.64 and 0.68 mm +/- 0.97 for the sirolimus-eluting stent group and the bare stent group, respectively (P = .20). The binary restenosis rates, with a cutoff of 50% at 6 months, were zero in the sirolimus-eluting stent group and 7.7% in the bare stent group (P = .49). Clinical outcomes matched angiographic outcomes with improvements in ankle-brachial index and symptoms of claudication. There was no significant difference between treatments in terms of adverse events. CONCLUSION Although there is a trend for greater efficacy in the sirolimus-eluting stent group, there were no statistically significant differences in any of the variables.

Drug eluting stents-potential applications for peripheral arterial occlusive disease

Many different approaches have been evaluated to prevent restenosis in stents after vascular implantation. Currently, drug-eluting stents are extremely promising in suppressing neointimal hyperplasia. Various animal studies and randomized trials in humans have shown excellent results in terms of safety and efficacy during intermediate-term follow-up. This article will give an overview of experimental and clinical data of the different agents in published and ongoing trials.

PTFE-covered self-expanding nitinol stents for the treatment of severe iliac and femoral artery stenoses and occlusions: final results from a prospective study.

Purpose: To evaluate the technical performance, safety, and 1-year clinical efficacy of polytetrafluoroethylene (PTFE)-covered nitinol stents in the treatment of atherosclerotic iliac and superficial femoral artery (SFA) disease. Methods: The multicenter, prospective, nonrandomized COVENT study involved 98 patients (70 men; mean age 64±10 years) who received PTFE-covered nitinol stents in 107 arteries (60 iliac and 47 SFAs) after predilation. The average lesion length was 50 mm in the SFA and 45 mm in the iliac arteries. Postdilation was performed when necessary. Duplex ultrasound and ankle-brachial index (ABI) were performed at discharge and at 1, 6, and 12 months in follow-up. Results: In total, 130 stents were placed successfully in 97 (99%) of 98 patients. One stent was misplaced during deployment and required subsequent surgical removal. The average stenosis grade was reduced from 98% to 6% in the SFAs and from 96% to 4% in the iliac arteries after covered stent placement. There was a significant rise of the mean ABI from 0.64 at baseline to 0.97 and 0.95 at 1 and 12 months, respectively (p < 0.001). There were 7 primary covered stent occlusions (6.5% of 107 stented lesions: 3 not treated, 2 bypassed, 2 dilated or stented) and 5 (4.7%) recurrent in-stent occlusions (1 bypassed, 2 dilated, 2 untreated) during the 1-year follow-up. Primary patency rates were 92% at 6 months and 89.8% at 12 months for the entire cohort. Secondary patency rates were 98% and 95.6%, respectively. No statistically significant differences were observed in the primary patency rates for the SFAs (89.3% at both 6 and 12 months) versus the iliac arteries (94.3% at 6 months and 90.7% at 12 months). Conclusions: Primary implantation of PTFE-covered nitinol stents in the iliac and superficial femoral arteries is technically feasible, safe, and effective, with excellent 1-year patency.

Technical report and preliminary clinical data of a novel catheter for luminal re-entry after subintimal dissection.

Rationale and Objectives:The objective of this study was to evaluate the safety and the effectiveness of the Outback catheter for intraluminal re-entry after subintimal dissection in the crossing of chronic arterial occlusions. Methods:This study was a proof-of-concept feasibility. Ten patients with totally occluded arteries in the iliac artery to the distal femoral artery (mean occlusion length, 13.1 cm; range, 5–25 cm) were treated with the novel catheter. After successful re-entry, PTA or PTA plus stenting was performed. Results:No perforations, dissections, lacerations, or device complications occurred. The procedural re-entry success rate with the Outback catheter was 50% (5/10 patients). Conclusions:Although the Outback catheter is safe, the percentage of intraluminal reaccess should be ameliorated through engineering improvements because there is some evidence to suggest that subintimal recanalization could produce improved long-term results.

Evaluation of various image reconstruction parameters in lower extremity stents using multidetector-row CT angiography: initial findings

Image quality, visible lumen and patency of lower limb stents was assessed by multidetector-row computed tomography (MDCT) angiography using various reconstruction parameters and the results compared with conventional angiography. Fourteen patients (25 stents) were evaluated. From MDCT datasets, axial and coronal oblique reformations were reconstructed using differing reconstruction parameters (slice thickness, kernel, views). Artifacts and image quality were assessed using a five-degree scale (1=excellent, 5=poor). Visible stent diameter was measured. Stenosis severity was compared with calibrated catheter angiography. The image quality of medium and sharp image kernels were good/fair (1.9–2.4), while smooth kernel provided only acceptable/poor image quality (3.9–4.4). Coronal oblique images were rated superior to assess in-stent lumen rather than axial. Using medium and sharp kernels, the visible stent lumen was significantly greater than using smooth kernel (P<0.001). thirteen out of fourteen patients (24/25 stents) were correctly classified as patent. In one patient, in-stent stenosis (≥50%) was falsely diagnosed using CT angiography (CTA) with smooth kernel and was, therefore, rated as false positive. Coronal oblique views, as well as medium and sharp kernels, have shown the best results regarding image quality to assess stent patency in the lower limb. Therefore, MDCT could be a valuable non-invasive modality for stent imaging in the peripheral vasculature.

Comparison of Digital Flat-Panel Detector and Conventional Angiography Machines: Evaluation of Stent Detection Rates, Visibility Scores, and Dose-Area Products

OBJECTIVE The objective of this study was to compare the performance and radiation doses of a flat-panel detector (FPD) angiography machine with an image intensifier (II) angiography machine. MATERIALS AND METHODS Images of four nitinol stents (Sinus-SuperFlex, SMART, Luminexx, and Zilver stents) in a phantom of a human pelvis were acquired on an FPD system (Axiom Artis) and an II system (Fluorospot TOP) using the following modes: spot-film, continuous fluoroscopy (4, 7.5, 15, and 30 pulses/s), and three amplification modes. Objective stent detection rates and subjective radiopacity scores (scale: 0 [not visible] to 4 [excellent visibility]) were calculated. The radiation doses evaluated by the respective machines were compared. RESULTS Over all modes and stents, the mean objective correct stent detection rates and mean subjective radiopacity scores were 89.49% and 1.81, respectively, for the Axiom Artis and 91.00% and 2.26 for the Fluorospot TOP. The stent detection rates over all modes for the SMART and Luminexx stents were better using the Axiom Artis machine (97.61% vs 93.55% and 98.28% vs 90.41%, respectively) and those for the Sinus-SuperFlex and Zilver stents were better using the Fluorospot TOP machine (90.83% vs 83.56% and 89.29% vs 80.50%). The subjective radiopacity scores of stent visibility were worse for the Axiom Artis than the Fluorospot TOP for all stents except the Luminexx stent (mean score, 2.34 vs 2.21, respectively). The objective stent detection rates and subjective radiopacity scores improved using the spot-film mode and with raising amplification, whereas increases in the fluoroscopy pulsing frequency did not improve stent detection rates or radiopacity scores for either machine. The radiation doses at continuous fluoroscopy were approximately 90% higher for the Axiom Artis than for the Fluorospot TOP (2.60 vs 1.41 μGy/m(2) at 30 pulses/s, respectively). CONCLUSION The objective correct stent detection rates were similar for both machines with differences in detection for the respective stents. The subjective radiopacity scores were almost always better for the Fluorospot TOP machine. Also, the Axiom Artis machine generated approximately 90% higher radiation doses in fluoroscopy. For both machines, using a higher fluoroscopy pulsing frequency had no positive effect on objective correct stent detection rates or subjective radiopacity scores.

Superficial femoral artery: current treatment options

Treatment of the superficial femoral artery (SFA) has been among the least effective of all endovascular procedures in terms of long-term patency. The relatively small vessel lumen, in conjunction with a high plaque burden, slow flow, and a high frequency of primary occlusions, contributes to a considerable rate of acute technical failures. Because of these technical limitations a much effort has been made during the past years. This manuscript should summarize the hopes and limitations of different approaches such as brachytherapy, cutting balloons, stents and stent grafts, drug-eluting stents, and drug-coated balloons.

Effects of MRI contrast agents on human embryonic lung fibroblasts.

Rationale and Objectives:The objective of this investigation was to evaluate 6 magnetic resonance contrast media (CM) with regard to their different effects on human embryonic lung fibroblasts (HEL-299). Methods:Human embryonic fibroblasts (HEL-299) were incubated with 1×, 5×, 10×, and 20× of the normal molar blood concentration (1×, 5×, 10×, 20× conc.) reached through routine contrast media applications for MRI examinations. Four gadolinium-based CM, ie, Gadovist, Magnevist, Multihance, Omniscan, Teslascan (Manganese-based), and Resovist (Iron-based), with incubation periods over 4 hours and 24 hours were investigated. Proliferation kinetics, colony formation, and viability assays were performed after 4 and 24 hours of treatment. Apoptotic cells were quantified after tetramethylrhodamine ethyl ester staining following 24 hours of CM media incubation (20× conc.) by fluorescence activated cell sorting cytometry. Furthermore, immunofluorescence images with vimentin staining were obtained (20× conc., 24 hours treatment). Cell cycle analysis was performed after 24 hours of incubation and 20× conc. directly after incubation and 24 hours later (fluorescence activated cell sorting cytometry). Results:The proliferation kinetics performed with 20× conc. revealed a persistent increase in cell numbers until day 11 for all CM without significant differences after 4 hours of incubation. A significant reduction in initial cell numbers was recorded in the 24-hours-group after 4 days of CM incubation with Magnevist, Multihance, Omniscan, and Teslascan. Solely cells incubated with Resovist and Gadovist failed to show decreased cell numbers when compared with the control group. However, a considerable cell regain occurred afterward reaching control-group levels on day 21. Colony numbers were significantly reduced (about 20%, respectively) with Magnevist at 10× and 20× conc., as well as Omniscan and Multihance at 20× conc. when compared with all other groups, P < 0.05. Cell-cycle distribution showed a reduction of S-phase cells for Magnevist, Omniscan, and Multihance (2.9%–10.5%) when compared with Gadovist, Resovist and Teslascan (16.7%–21.0%). Twenty-four hours after incubation, the percentiles of cells in S-phase were significantly increased for Magnevist, Omniscan, and Multihance (31.4%–38.5%) when compared with Gadovist, Resovist, and Teslascan (18.6%–26.8%), P < 0.05. Viability was not impaired by administration of any CM and no apoptosis was seen after tetramethylrhodamine ethyl ester staining at 24 hours of incubation. Cell morphology remained unchanged in vimentin-staining for all CM and conditioning regimens. Conclusions:No toxic effects on embryonic fetal lung fibroblasts were detectable after 4 and 24 hours of incubation in 6 MRI CM and 10× to 20× conc. in our setting. Antiproliferative effects, initially detected with Magnevist, Omniscan and Multihance, were rapidly compensated for.