Dimitris Siablis

A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial.

OBJECTIVES The study investigated the efficacy and safety of a balloon expandable, sirolimus-eluting stent (SES) in patients with symptomatic infrapopliteal arterial disease. BACKGROUND Results of infrapopliteal interventions using balloon angioplasty and/or bare stents are limited by a relatively high restenosis rate, which could be potentially improved by stabilizing the lesion with a SES. METHODS Two hundred patients (total lesion length 27 ± 21 mm) were randomized to infrapopliteal SES stenting or percutaneous transluminal balloon angioplasty (PTA). The primary endpoint was 1-year in-segment binary restenosis by quantitative angiography. RESULTS Ninety-nine and 101 patients (mean age 73.4 years; 64% diabetics) were randomized to SES and PTA, respectively (8 crossover bailout cases to SES). At 1 year, there were lower angiographic restenosis rates (22.4% vs. 41.9%, p = 0.019), greater vessel patency (75.0% vs. 57.1%, p =0.025), and similar death, repeat revascularization, index-limb amputation rates, and proportions of patients with improved Rutherford class for SES versus PTA. CONCLUSIONS SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease.

Sirolimus-Eluting versus Bare Stents for Bailout after Suboptimal Infrapopliteal Angioplasty for Critical Limb Ischemia: 6-Month Angiographic Results from a Nonrandomized Prospective Single-Center Study

Purpose: To report the 6-month angiographic results from a prospective single-center study investigating the efficacy and outcome of sirolimus-eluting stents used for bailout after infrapopliteal revascularization of patients with critical limb ischemia (CLI). Methods: Twenty-nine patients (21 men; mean age 68.7 years) underwent infrapopliteal revascularization with bare metal stents (group B) implanted for bailout in 65 lesions (38 stenoses and 27 occlusions) in 40 infrapopliteal arteries. Another 29 patients (21 men; mean age 68.8 years) underwent infrapopliteal bailout stenting with sirolimus-eluting stents (group S) in 66 lesions (46 stenoses and 20 occlusions) in 41 vessels. Preliminary 6-month angiographic and clinical results were analyzed. Results: Hyperlipidemia and symptomatic cardiac and carotid diseases were more pronounced in group S (p < 0.05). Technical success was 96.6% (28/29 limbs) in group B versus 100.0% in group S (p=0.16). Six-month primary patency was 68.1% in group B versus 92.0% in group S (p < 0.002). Binary in-stent and in-segment restenosis rates were 55.3% and 66.0%, respectively, in patients with bare stents versus 4.0% and 32.0%, respectively, in patients treated with the sirolimus-eluting stents (both p < 0.001). The target lesion reintervention rate at 6 months was 17.0% in group B versus 4.0% in group S (p=0.02). Limb salvage was 100% in both groups. Six-month mortality and minor amputation rates were 6.9% and 17.2%, respectively, in group B versus 10.3% and 3.4%, respectively, in group S (p=0.32 and p=0.04, respectively). Conclusions: Sirolimus-eluting stents seem to restrict neointimal hyperplasia in the infrapopliteal vascular bed.

Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: enduring 1-year angiographic and clinical benefit.

Purpose: To report the 1-year angiographic and clinical outcome from a prospective single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia (CLI) who underwent below-the-knee endovascular revascularization. Methods: Stenting was performed as a bailout procedure for suboptimal angioplasty results (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis >30%). In the first 29 patients, infrapopliteal stenting was performed with bare metal stents (group B) and with sirolimus-eluting stents in the other 29 patients (group S). Results: Below-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities (hyperlipidemia and symptomatic cardiac and carotid disease) were more pronounced in group S (p<0.05). At 6 months, sirolimus-eluting stents demonstrated significantly higher primary patency (OR 5.625, 95% CI 1.711 to 18.493, p=0.004) and decreased in-stent binary restenosis (OR 0.067, 95% CI 0.021 to 0.017, p<0.001) and in-segment binary restenosis (OR 0.229, 95% CI 0.099 to 0.533, p=0.001). After 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (OR 10.401, 95% CI 3.425 to 31.589, p<0.001) and significantly less in-stent (OR 0.156, 95% CI 0.060 to 0.407, p<0.001) and in-segment (OR 0.089, 95% CI 0.023 to 0.349, p=0.001) binary restenosis. In addition, sirolimus-eluting stents were associated with significantly fewer cumulative target lesion reinterventions at 6 months (OR 0.057, 95% CI 0.008 to 0.426, p=0.005) and 1 year (OR 0.238, 95% CI 0.067 to 0.841, p=0.026). No significant differences between groups B and S were noted at 1 year with respect to mortality (10.3% versus 13.8%, respectively), minor amputation (17.2% versus 10.3%), or limb salvage (100% versus 96%). Conclusion: The application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment.

Paclitaxel-Coated Balloon Angioplasty vs. Plain Balloon Dilation for the Treatment of Failing Dialysis Access: 6-Month Interim Results From a Prospective Randomized Controlled Trial:

Purpose To report the 6-month results of a prospective randomized trial investigating angioplasty with paclitaxel-coated balloons (PCB) vs. plain balloon angioplasty (BA) for the treatment of failing native arteriovenous fistulae (AVF) or prosthetic arteriovenous grafts (AVG). Methods The enrollment criteria for this non-inferiority hypothesis trial included clinical signs of failing dialysis access with angiographic documentation of a significant venous stenotic lesion in patients with AVF or AVG circuits. From March to December 2010, 40 patients (29 men; mean age 64.1±14.3 years) were randomized to undergo either PCB dilation (n=20) or standard BA (n=20) of a stenosed venous outflow lesion. Regular angiographic follow-up was scheduled bimonthly. Study outcome measures included device success (<30% residual stenosis without postdilation), procedural success (<30% residual stenosis), and primary patency of the treated lesion (<50% angiographic restenosis and no need for any interim repeat procedures). Results Baseline and procedural variables were comparably distributed between both groups. Device success was 9/20 (45%) for the PCB device vs. 20/20 (100%) for standard control BA (p<0.001). Procedural success was 100% in both groups after further high-pressure post-dilation as necessary. There were no major or minor complications in either group. At 6 months, cumulative target lesion primary patency was significantly higher after PCB application (70% in PCB group vs. 25% in BA group, p<0.001; HR 0.30, 95% CI 0.12 to 0.71, p<0.006). Conclusion PCB angioplasty improves patency after angioplasty of venous stenoses of failing vascular access used for dialysis.

Distal embolism during percutaneous revascularization of infra-aortic arterial occlusive disease: an underestimated phenomenon.

Purpose: To investigate distal embolism during endovascular procedures of the infra-aortic arteries by utilizing a commercial filter basket and unveil any correlation between the baseline clinical and procedural variables and the histopathological findings of the collected particles. Methods: In a prospective study, 48 patients (37 men; mean age 70.8±7.8 years, range 50–83) underwent endoluminal therapy of infra-aortic lesions (stenosis >75% or occlusion; mean lesion length 52.2±38.0 mm) with standard endovascular procedures. A nitinol filter basket (n=50) was employed for distal protection. The collected particles were histopathologically analyzed. The harvested specimens were quantified after digital image post processing. Results: Procedural success of filter-protected revascularization was 93.8%. Three failures included 1 vasospasm, 1 distal embolus, and 1 side-branch occlusion. The total area of retrieved particles per basket was 2.76±6.49 mm2 (range 0.0–40.3). Particles with a major axis >1 and >3 mm were detected in 29 (58.0%) and 6 (12.0%), respectively, of the examined filters. Collected particles consisted primarily of platelets and fibrin conglomerates, trapped erythrocytes, inflammatory cells, and extracellular matrix. Increased lesion length, increased reference vessel diameter, acute thromboses, and total occlusions were positively correlated with higher amounts of captured particles (p<0.05). Multivariate analysis incriminated declotting procedures as the only independent predictor of increased embolic burden (p<0.05). Conclusion: The embolism phenomenon during infra-aortic interventions is frequent and underestimated. The liberated particles consisted primarily of atheromatous plaque elements and thrombus. The reported data might support the application of a protective filter basket in selected subsets of lesions with a riskier embolic profile and whenever declotting procedures are performed.

Primary Everolimus-Eluting Stenting Versus Balloon Angioplasty With Bailout Bare Metal Stenting of Long Infrapopliteal Lesions for Treatment of Critical Limb Ischemia

Purpose: To report the long-term outcomes of a single-center prospective study investigating primary placement of everolimus-eluting metal stents for recanalization of long infrapopliteal lesions compared to a matched historical control group treated with plain balloon angioplasty and provisional placement of bare metal stents in a bailout manner. Methods: The study included 81 patients (63 men; mean age 71 years, range 45–85) suffering from critical limb ischemia (CLI) and angiographically proven long-segment (at least 1 lesion >4.5 cm) de novo infrapopliteal artery disease who underwent below-the-knee revascularization with either primary placement of everolimus-eluting stents (n = 47, 51 limbs, 102 lesions) or angioplasty and bailout bare metal stenting (n=34, 36 limbs, 72 lesions). Clinical and angiographic follow-up was collected at regular time intervals. Primary clinical and angiographic endpoints included patient survival, major amputationfree survival, angiographic primary patency, angiographic binary restenosis (>50%), and overall event-free survival. Results were stratified according to endovascular treatment received. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity. Results: Baseline demographics were well matched. No significant differences were identified between the 2 groups with regard to overall 3-year patient survival (82.2% versus 65.7%; p=0.90) and amputation-free survival (77.1% versus 86.9%; p=0.20). Up to 3 years, lesions fully covered with everolimus-eluting stents were associated with significantly higher primary patency [hazard ratio (HR) 7.98, 95% CI 3.69 to 17.25, p<0.0001], reduced binary restenosis (HR 2.94, 95% CI 1.74 to 4.99, p<0.0001), and improved overall event-free survival (HR 2.19, 95% CI 1.16 to 4.13, p=0.015) versus the matched historical control group. Conclusion: Primary infrapopliteal everolimus-eluting stenting for CLI treatment significantly inhibits restenosis and improves long-term angiographic patency and overall patient event-free survival compared to balloon angioplasty and bailout bare metal stenting.

Incidence, anatomical location, and clinical significance of compressions and fractures in infrapopliteal balloon-expandable metal stents.

Purpose: To investigate the incidence, anatomical location, and clinical impact of fractures and/or compression of infrapopliteal balloon-expandable metal stents implanted for critical limb ischemia (CLI) treatment. Methods: This prospective study included 63 CLI patients (45 men; mean age 71.3±9.5 years) who had been treated with infrapopliteal angioplasty and stent placement for 191 lesions in 84 limbs. In all, 369 stents (296 stainless steel and 73 cobalt-chromium alloy) were implanted; 239 were placed overlapping in tandem lesions. Mean length of the overall stented segment was 4.4±6.3 cm (range 1.6–14.0). Stents were located in the tibioperoneal (n=34), anterior tibial (n=195), posterior tibial (n=63), and peroneal (n=77) arteries. Follow-up consisted of digital subtraction angiography and infrapopliteal radiography imaging at 2 different angles. Evaluation of stents for the presence of fracture and/or compression was done after digital processing at the highest possible magnification. Stent fractures were defined according to published standards, whereas compression was classified as severe shape alteration and/or collapse of the stent mesh. Angiographic restenosis was based on a 50% threshold. Results: Mean follow-up was 15±11 months (range 6–60). Image analysis detected 1 (0.3%) severe stent fracture (complete separation and misalignment of stent struts) and 11 (3.0%) stent compressions. Infrapopliteal stent fracture and compressions were associated with increased artery restenosis [100% (12/12) versus 47.3% (169/357), p<0.001] and an increased rate of clinical deterioration and clinically-driven reinterventions [41.7% (5/12 limbs) versus 19.4% (14/72 limbs), p=0.04]. The single fracture and most of the compressions were located in the distal third of the anterior tibial artery. Conclusion: Stent fractures and compressions of infrapopliteal balloon-expandable metal stents are infrequent. However, they may be related to increased restenosis.

AngioJet Rheolytic Thrombectomy Versus Local Intrapulmonary Thrombolysis in Massive Pulmonary Embolism: A Retrospective Data Analysis

Purpose: To compare the efficacy of full-dose local intrapulmonary thrombolysis (LIT) versus AngioJet rheolytic thrombectomy (ART) in the treatment of massive pulmonary embolism. Methods: A retrospective review was conducted of 8 consecutive patients (5 women; mean age 66.0±5.9 years, range 56–74) who underwent LIT with high-dose intrapulmonary urokinase (4400 IU/kg over 10 minutes followed by a 2000-IU/kg/h infusion) and a subsequent 6 consecutive patients (4 men; mean age of 59.2±17.0 years, range 26–69) who underwent ART plus adjunctive low-dose urokinase infusions (100,000 IU) until hemodynamic recovery was achieved. Pre and postprocedural Miller scores were calculated, and relative Miller score improvement, total urokinase doses, and duration of therapy were compared. Results: Hemodynamic stability was restored in all 8 LIT patients and in 5 (83%) of the 6 ART patients; 1 (16.7%) patient died during the ART procedure due to recurrent MPE. In the LIT group, the mean Miller score prior to intervention was 17.38±2.67, which was reduced to 6.13±1.46 after the intervention (p < 0.0001) compared to scores of 18.83±2.86 and 6.83±2.79, respectively, in the ART group (p < 0.0001). The mean urokinase dose was 2.07±0.44 million IU in the LIT group versus 0.70±0.36 million IU in the ART group (p < 0.0001). The mean duration of therapy was 11.45±2.94 hours in the LIT group versus 3.37±1.41 hours in the ART group (p < 0.0001). No significant difference in relative Miller score improvement was observed. Conclusion: By accelerating the fragmentation of thrombus, ART plus adjunctive low-dose urokinase seems to be more rapidly effective compared to LIT. ART achieves both rapid cardiovascular relief and reduces the dose of thrombolytic agent necessary in patients with massive pulmonary embolism.

Quality Improvement Guidelines for Percutaneous Catheter-Directed Intra-Arterial Thrombolysis and Mechanical Thrombectomy for Acute Lower-Limb Ischemia

Percutaneous catheter-directed intra-arterial thrombolysis is a safe and effective method of treating acute and subacute lower limb ischemia, as long as accurate patient selection and procedural monitoring are ensured. Although larger, controlled trials are needed to establish the role of PTDs in ALI, mechanical thrombectomy could currently be applied combined with lytic infusion in selected cases where rapid recanalization is required or as a stand-alone therapy when the administration of thrombolytic agents is contraindicated.

Drug-eluting versus plain balloon angioplasty for the treatment of failing dialysis access: Final results and cost-effectiveness analysis from a prospective randomized controlled trial (NCT01174472)

OBJECTIVE To report the final results and cost-effectiveness analysis of a prospective randomized controlled trial investigating drug-eluting balloon (DEB) versus plain balloon angioplasty (BA) for the treatment of failing dialysis access (NCT01174472). METHODS 40 patients were randomized to angioplasty with either DEB (n=20) or BA (n=20) for treatment of significant venous stenosis causing a failing dialysis access. Both arteriovenous fistulas (AVF) and synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was scheduled every two months. Primary endpoints were technical success and target lesion primary patency at 1 year. Cumulative and survival analysis was performed. Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER) were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn. RESULTS Baseline variables were equally distributed between the two groups. At 1 year, cumulative target lesion primary patency was significantly higher after DEB application (35% vs. 5% after BA, p<0.001). Overall, median primary patency was 0.64 years in case of DEB vs. 0.36 years in case of BA (p=0.0007; unadjusted HR=0.27 [95%CI: 0.13-0.58]; Cox adjusted HR=0.23 [95%CI: 0.10-0.50]). ICER was 2198 Euros (€) per primary patency year of dialysis access gained. INB was 1068€ (95%CI: 31-2105€) for a willingness-to-pay (WTP) threshold of 5000€ (corresponding acceptability probability >97%). CONCLUSION DEB angioplasty may be a cost-effective option that significantly improves patency after angioplasty of venous stenoses of failing vascular dialysis access. Further large-scale randomized trials are warranted.