Wound Healing Outcomes and Health-Related Quality-of-Life Changes in the ACHILLES Trial: 1-Year Results From a Prospective Randomized Controlled Trial of Infrapopliteal Balloon Angioplasty Versus Sirolimus-Eluting Stenting in Patients With Ischemic Peripheral Arterial Disease.

OBJECTIVES: The authors sought to report the wound healing outcomes, health-related quality-of-life changes and quality-adjusted life-years (QALYs) gain in the 2 treatment arms of the ACHILLES (Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease) multicenter randomized trial. BACKGROUND: The ACHILLES randomized trial has previously shown that sirolimus-eluting stents (SES) may achieve lower vessel restenosis and higher event-free survival rates compared with plain balloon angioplasty (PTA) for infrapopliteal lesions. METHODS: A total of 200 patients were randomly assigned between SES and PTA for the treatment of infrapopliteal arterial occlusive lesions. Progression of wound healing was serially assessed by digital photography. Health-related quality-of-life scores were assessed with the self-administered EQ-5D questionnaire up to 1 year from randomization. QALYs gained were calculated with a standard multiplicative model using distribution-free Bayesian modeling. RESULTS: In total, 109 open wounds (n = 54 in SES; n = 55 in PTA) were documented at baseline. At 6 months, wound volume reduction (%) was significantly higher in the SES group (95% healing [95% confidence interval (CI): 80% to 99%] compared with 60% healing [95% CI: 13% to 90%] in the PTA group; p = 0.048). At 1 year, rates of complete wound closure were higher in the case of SES (72.9% vs. 55.6% closed wounds in PTA; p = 0.088). The recorded weighted EQ-5D score improved significantly up to 1 year in case of SES (p < 0.0001), but not in case of PTA. There was a trend of more QALYs gained with SES compared with PTA up to 1 year after randomization. Relative QALY gain was 0.10 (95% CI: -0.01 to 0.21; p = 0.08) in the whole study and 0.17 (95% CI: -0.03 to 0.35; p = 0.09) in the wound subgroups comparison. CONCLUSIONS: Infrapopliteal SES accelerates wound healing and may improve quality of life compared with PTA. (Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease [ACHILLES]; NCT00640770).

Long-Term Clinical Outcomes of Infrapopliteal Drug-Eluting Stent Placement for Critical Limb Ischemia in Diabetic Patients.

PURPOSE: To evaluate long-term clinical outcomes of infrapopliteal drug-eluting stent (DES) placement in insulin-dependent and non-insulin-dependent diabetic patients with critical limb ischemia (CLI). MATERIALS AND METHODS: A retrospective analysis was performed of all diabetic patients treated with infrapopliteal DES between January 2002 and September 2012. The study's primary outcome measures were patient survival and major amputation-free survival (AFS). Secondary outcome measures included technical success (defined as the creation of a straight line of blood flow to the foot arch with < 30%), identification of independent predictors of primary outcomes, infrapopliteal target limb repeat intervention-free survival, and procedure-related complications. RESULTS: In total, 214 patients with CLI (168 men [78.5%]; mean age, 70 y ± 9) in 311 limbs, 562 arteries, and 679 lesions were treated. According to Kaplan-Meier analysis, survival rates were 90.8%, 55.5%, and 36.2%, and AFS rates were 94.9%, 90.4%, and 90.4%, respectively, at 1, 5, and 10 years. Target limb repeat intervention-free survival rates were 79.7%, 55.2%, and 49.7%, respectively, at 1, 5, and 10 years. The overall technical success rate was 97.7%. Cox multivariate analysis demonstrated that procedural failure was the only independent predictor of decreased AFS (hazard ratio [HR], 61.3; 95% confidence interval [CI], 13.8-271.9), and statin use was associated with increased survival (HR, 0.55; 95% CI, 0.31-0.98). Coronary disease (HR, 1.9; 95% CI, 1.01-3.54), dialysis (HR, 2.2; 95% CI, 1.21-4.06), and duration of diabetes (HR, 1.5; 95% CI, 1.02-2.34) were identified as independent predictors of decreased survival. Major complications occurred in four of 479 procedures (0.8%). CONCLUSIONS: Infrapopliteal DES placement for the management of CLI in diabetic patients resulted in a 55.5% 5-year survival rate, with a 90.4% AFS at 5 and 10 years and a 50.3% repeat intervention rate at 10 years. Technical failure was associated with reduced AFS, and statin intake was associated with increased survival.

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.

Paclitaxel-coated versus plain balloon angioplasty for dysfunctional arteriovenous fistulae: one-year results of a prospective randomized controlled trial.

PURPOSE: To report 1-year results of a single-center randomized controlled trial comparing paclitaxel-coated balloon (PCB) versus high-pressure plain balloon angioplasty for the treatment of failing arteriovenous fistulae (AVFs). MATERIALS AND METHODS: Forty patients (26 men; mean age, 61 y ± 14.63) were randomized at 1:1 to undergo PCB (n = 20) or high-pressure balloon (HPB; n = 20) angioplasty of dysfunctional AVFs. There were no significant differences in baseline demographics between groups. Enrollment required a clinical diagnosis of a dysfunctional AVF attributed to a single stenotic lesion verified with digital subtraction angiography. Primary endpoints included device success, anatomic success, clinical success, and target lesion revascularization (TLR)-free survival. Secondary endpoints included dialysis circuit primary patency and procedure-related complication rates. RESULTS: Device success rates were 100% in the HPB group and 35% in the PCB group (P < 0001): further dilation with an HPB was needed to achieve anatomic success in 13 of 20 cases in the PCB group (65%). Anatomic and clinical success rates were 100% in both groups. TLR-free survival (PCB, 308 d; HPB, 161 d; hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.236-0.966; P = .03) and access circuit primary patency (PCB, 270 d; HPB, 161 d; HR, 0.479; 95% CI, 0.237-0.968; P = .04) were significantly in favor of PCB angioplasty. No minor or major procedure-related complications occurred. CONCLUSIONS: In this single-center study, the use of PCBs resulted in superior TLR-free survival and dialysis access circuit primary patency of dysfunctional AVFs. However, additional HPB postdilation was required in the majority of cases.

Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the IDEAS randomized controlled trial.

OBJECTIVES: This study sought to report the results of a prospective randomized controlled trial comparing paclitaxel-coated balloons (PCB) versus drug-eluting stents (DES) in long infrapopliteal lesions. BACKGROUND: DES have an established role in the treatment of short infrapopliteal lesions, whereas there is increasing evidence for the use of PCB in longer below-the-knee lesions. METHODS: Inclusion criteria were patients with Rutherford classes 3 to 6 and angiographically documented infrapopliteal disease with a minimum lesion length of 70 mm. The primary endpoint was target lesion restenosis >50% assessed by digital angiography at 6 months. Secondary endpoints included immediate post-procedure stenosis and target lesion revascularization. RESULTS: Fifty patients were randomized to undergo infrapopliteal PCB angioplasty (25 arteries in 25 limbs; PCB group) or primary DES placement (30 arteries in 27 limbs; DES group). Immediate residual post-procedure stenosis was significantly lower in DES (9.6 ± 2.2% vs. 24.8 ± 3.5% in PCB; p < 0.0001). At 6 months, 5 patients died (2 in PCB vs. 3 in DES; p = 1.00) and 3 suffered a major amputation (1 in PCB vs. 2 in DES; p = 1.00). In total, 44 angiograms were evaluable with quantitative vessel analysis. Binary (>50%) angiographic restenosis rate was significantly lower in DES (7 of 25 [28%] vs. 11 of 19 [57.9%] in PCB; p = 0.0457). There were no significant differences with regard to target lesion revascularization (2 of 26 [7.7%] in DES vs. 3 of 22 [13.6%] in PCB; p = 0.65). Positive vessel wall remodeling was observed in 3 cases in the PCB arm (3 of 19 [(15.8%)] vs. 0 of 19 [0%] in DES; p = 0.07). CONCLUSIONS: Compared with PCB in long infrapopliteal lesions, DES are related with significantly lower residual immediate post-procedure stenosis and have shown significantly reduced vessel restenosis at 6 months. PCB may produce positive vessel remodeling. (Infrapopliteal Drug-Eluting Angioplasty Versus Stenting [IDEAS-I]; NCT01517997).

Distal macro- and microembolization during subintimal recanalization of femoropopliteal chronic total occlusions.

PURPOSE: To investigate the phenomenon of distal embolization during subintimal angioplasty with or without stenting of femoropopliteal chronic total occlusions (CTOs). METHODS: This prospective study included 40 consecutive patients (35 men; mean age 65.4±9.3 years) who underwent subintimal angioplasty alone (n=14) or with stenting (n=26) of CTOs in the femoropopliteal segment. A Spider protection filter was used to capture any possible macro- or microemboli generated during balloon inflation/stenting. Arterial outflow was angiographically checked during each consecutive procedural step. All filters were examined on site for macroscopic material, while the first 20 filters underwent further histopathological qualitative and semiquantitative analysis using a 0+ to 3+ score. RESULTS: There was no angiographically or clinically evident distal embolization. Macroscopic particulate debris was not detected in any filter. Histopathology confirmed the absence of macroemboli but revealed microembolic material (diameter <100 µm) in all filters (20/20). The mean number of particles detected was 9.4±4.5 (range 5-17). Histopathological findings included fibrin conglomerates (20/20), trapped erythrocytes (19/20), inflammatory cells (16/20), calcification minerals (6/20), extracellular matrix (6/20), cholesterol clefts (6/20), and endothelial cells (6/20). Captured material was classified as fresh and old thrombus in 7/20 and 4/20 cases, respectively. Semiquantitative analysis demonstrated that the collected microparticles consisted primarily of fibrin conglomerates (median score 2+), trapped erythrocytes (median score 1+), and inflammatory cells (median score 1+). CONCLUSION: Macroscopically evident emboli were not detected following subintimal angioplasty or stenting of femoropopliteal CTOs. Microscopic debris was present in all filters. The clinical significance of the phenomenon remains to be determined.

Initial experience with ticagrelor in patients with critical limb ischemia and high on-clopidogrel platelet reactivity undergoing complex peripheral endovascular procedures.

PURPOSE: To investigate the safety and efficacy of ticagrelor in patients with critical limb ischemia (CLI) and high on-clopidogrel platelet reactivity (HCPR) undergoing complex, limb-salvage, peripheral endovascular procedures (PEP). MATERIALS AND METHODS: The study included consecutive patients with HCPR undergoing PEP for CLI. HCPR was defined as platelet reaction units (PRU) >234 as assessed by the VerifyNow P2Y12 assay. Patients with HCPR were prescribed ticagrelor, 180/90 mg twice daily, and aspirin, 100 mg daily, for 6 months and ticagrelor, 180/90 mg twice daily, thereafter. Primary safety outcome was total major bleeding, and primary efficacy outcome was the composite of cardiovascular death and major amputation. Secondary outcomes included the level of platelet inhibition achieved and target limb revascularization (TLR)-free survival rate. RESULTS: In total, 37 CLI patients with 40 limbs were investigated. Mean follow-up period was 11.3 ± 5.0 months (range 6-21). The mean treated lesion length was 229.2 ± 71.4 mm in the femoropopliteal axis and 179.3 ± 83.9 mm in the infrapopliteal arteries. No major or minor bleeding was detected. There were four periprocedural minor adverse events (10.8%), and in two cases (5.6%) ticagrelor was discontinued. In all patients, ticagrelor achieved platelet inhibition lower than the cut-off value. Mean PRU during clopidogrel therapy was 308.4 ± 41.8 (range 257-422) versus 67.0 ± 52.8 (range 2-189) when switched to ticagrelor; p < 0.0001. Kaplan-Meier estimated primary efficacy outcome and TLR-free survival rates were 92.0 and 67.3% at 12 months, respectively. CONCLUSION: In this series of CLI patients with HCPR undergoing complex PEP, initial experience with ticagrelor was proven safe and efficient because it resulted in sufficient platelet inhibition and satisfactory clinical results without major complications.

Incidence of arterial micro-embolization during percutaneous AngioJet thrombectomy of hemodialysis grafts.

PURPOSE: This study was designed to investigate the incidence of arterial embolization using a peripheral protection filter device in a series of patients undergoing percutaneous mechanical thrombectomy for the management of thrombosed hemodialysis arteriovenous grafts (AVGs). METHODS: This prospective, single-center study included all eligible patients presenting during an 18-month period to undergo AVG percutaneous thrombectomy. Inclusion criteria was a recently thrombosed AVG with 2 cm of artery before the next arterial branching. Primary endpoint was the incidence of distal arterial macro- and micro-embolization determined by both digital subtraction angiography and histopathological analysis of the material collected. Secondary endpoints included quantitative measurements of the specimens using a 0+ (no material) to 3+ (maximum load) score. RESULTS: In total, 42 patients met the study's inclusion criteria. No procedure-related complications or angiographically evident arterial embolization were noted. Macroscopically evident material was present in 47.6% (20/42 filters). Histopathology demonstrated that the embolic material was primary consisted of fibrin conglomerates and platelets (median score: 1.5, confidence interval: 1.0-3.0), whereas inflammatory cells, trapped erythrocytes, extracellular matrix, cholesterol clefts, foam cells, necrotic core, and smooth muscle cells also were detected. Mean total area of embolic material was 5.04 mm(2) (range 0.05-5.21). The mean major axis of the largest particle was 1.83 mm (range 0.29-6.64), whereas 19% (8/42) contained particles with major axis >1 mm and 12% (5/42) with major axis >3 mm. CONCLUSIONS: In this study, the percentage of arterial micro-embolization was significantly higher than previously reported. However, the detrimental, long-term, clinical relevance remains to be determined.

NGF promotes hemodynamic recovery in a rabbit hindlimb ischemic model through trkA- and VEGFR2-dependent pathways.

Nerve growth factor (NGF) has been reported to play an important role in physiological and pathological angiogenesis. Based on these observations, we hypothesized that NGF may induce the formation of functional blood vessels in a hindlimb ischemic rabbit model. Hindlimb ischemia was induced in 34 rabbits bilaterally by endovascular embolization of femoral arteries. On the 7th, 14th, and 20th postembolization days, NGF was injected intramuscularly, in 1 ischemic limb, and vehicle was injected in the contralateral control limb. On the 40th day, newly developed collateral vessels (diameter >500 µm) were quantified by transauricular intraarterial subtraction angiography. Perfusion analysis of an in vivo dynamic computed tomography study was performed to the limbs to investigate the hemodynamic recovery of the distal ischemic tissues. Functional estimation of limb perfusion showed a statistically significant increase of blood flow and blood volume for NGF. However, the increase of the collateral vessels was not detectable angiographically, providing evidence for the existence of a NGF-stimulated capillary angiogenic network but not increase of arteriogenesis. The combination of NGF with either tropomyosin-related kinase type A or vascular endothelial growth factor receptor 2 antagonists abolished the NGF-induced hemodynamic recovery. These findings provide new insights into understanding the involvement of NGF in vascular formation and its applications in therapeutic angiogenesis.

Systematic review of infrapopliteal drug-eluting stents: a meta-analysis of randomized controlled trials.

INTRODUCTION: Drug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES. MATERIALS AND METHODS: PubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of ≥50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported. RESULTS: Three RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall event-free survival (72.2 vs. 57.3 %; pooled RR = 1.26, 95 % CI = 1.10-1.44, p = 0.0006; NNT = 6.7). CONCLUSION: DES for focal infrapopliteal lesions significantly inhibit vascular restenosis and thereby improve primary patency, decrease repeat procedures, improve wound healing, and prolong overall event-free survival.

Cost-effectiveness analysis of infrapopliteal drug-eluting stents.

INTRODUCTION: There are no cost-utility data about below-the-knee placement of drug-eluting stents. The authors determined the cost-effectiveness of infrapopliteal drug-eluting stents for critical limb ischemia (CLI) treatment. METHODS: The event-free individual survival outcomes defined by the absence of any major events, including death, major amputation, and target limb repeat procedures, were reconstructed on the basis of two published infrapopliteal series. The first included spot Bail-out use of Sirolimus-eluting stents versus bare metal stents after suboptimal balloon angioplasty (Bail-out SES).The second was full-lesion Primary Everolimus-eluting stenting versus plain balloon angioplasty and bail-out bare metal stenting as necessary (primary EES). The number-needed-to-treat (NNT) to avoid one major event and incremental cost-effectiveness ratios (ICERs) were calculated for a 3-year postprocedural period for both strategies. RESULTS: Overall event-free survival was significantly improved in both strategies (hazard ratio (HR) [confidence interval (CI)]: 0.68 [0.41-1.12] in Bail-out SES and HR [CI]: 0.53 [0.29-0.99] in Primary EES). Event-free survival gain per patient was 0.89 (range, 0.11-3.0) years in Bail-out SES with an NNT of 4.6 (CI: 2.5-25.6) and a corresponding ICER of 6,518 (range 1,685-10,112). Survival gain was 0.91 (range 0.25-3.0) years in Primary EES with an NNT of 2.7 (CI: 1.7-5.8) and an ICER of 11,581 (range, 4,945-21,428) per event-free life-year gained. Two-way sensitivity analysis showed that stented lesion length >10 cm and/or DES list price >1000 were associated with the least economically favorable scenario in both strategies. CONCLUSIONS: Both strategies of bail-out SES and primary EES placement in the infrapopliteal arteries for CLI treatment exhibit single-digit NNT and relatively low corresponding ICERs.

Stent-grafts versus angioplasty and/or bare metal stents for failing arteriovenous grafts: a cross-over longitudinal study.

BACKGROUND: A well-established method to preserve failing synthetic arteriovenous grafts (AVGs) dialysis accesses is percutaneous transluminal angioplasty (PTA). Nevertheless, the one-year primary patency rate following PTA is approximately 25%. This study was designed to compare the angiographic and clinical outcomes following stent-graft insertion versus angioplasty and/or bare metal stenting (BMS) of recurrently failing AVGs, because of anastomotic and/or venous outflow stenoses. METHODS: Self-expanding stent-grafts were deployed for the treatment of failing AVGs in case of recurrent stenosis after treatment with conventional angioplasty or bail-out BMS. Regular angiographic follow-up was scheduled every two months the first six months and every three months thereafter. Data from previous procedures on the same treatment site were retrieved from our database. Primary patency was defined as a functioning graft with a patent treatment site without angiographic restenosis >50% and without any subsequent repeat procedures. Outcome data were analyzed by Kaplan-Meier analysis. RESULTS: In total, 35 patients previously treated with angioplasty and/or BMS for the treatment of recurrent significant AVG stenosis (group PTA), underwent stent-graft placement of the same treatment site (group SG). Of those, 20 patients had undergone angioplasty and 15 bail-out BMS. Mean lesion length was 4.8±1.7cm. Primary patency was significantly improved in the SG group (Hazard Ratio [HR] = 0.2 [95% CI= 0.11-0.36], P=.0001) by log-rank test. The estimated six and 12-month patency rates were 76.9% vs. 25.7%, and 61.4% vs. 8.6% for groups SG and PTA respectively, (P<.0001). CONCLUSIONS: Stent-graft placement significantly improves primary patency of anastomotic and venous outflow stenoses in recurrently failing prosthetic arteriovenous grafts.

Below-the-ankle angioplasty and stenting for limb salvage: anatomical considerations and long-term outcomes.

PURPOSE: To report the long-term angiographic and clinical results in a series of below-the-ankle (BTA) angioplasty procedures and to present some biomechanical issues related to the unique anatomical geometry of the ankle. METHODS: We performed a retrospective analysis of BTA angioplasty procedures. Clinical end points included technical success, patient mortality, salvage of the treated foot, and repeat target lesion revascularization. Imaging end points included primary patency, binary restenosis of the target lesion at the 50% threshold, and stent integrity (stent fracture, deformation, or collapse). Univariate subgroup analysis was performed. RESULTS: In total, 40 limbs in 37 patients (age 73.5 ± 8.2 years) with critical limb ischemia were included and 42 inframalleolar lesions (4.2 ± 1.4 cm) were analyzed. Technical success was achieved in 95.2% (40 of 42). Provisional stent placement was performed in 45.2% (19 of 42). Two patients died, and two major amputations occurred up to 3 years. At 1 year, overall primary vessel patency was 50.4 ± 9.1%, lesion binary restenosis rate was 64.1 ± 8.3%, and repeat intervention-free survival was 93.6 ± 4.3% according to life table analysis of all treated lesions. Pairwise subgroup analysis showed that BTA self-expanding stents were associated with significantly higher restenosis and poorer primary patency compared to plain balloon angioplasty or sirolimus-eluting balloon-expandable stents. Significant deformation and/or fracture of balloon-expandable stents placed BTA were identified in five of 11. Dynamic imaging showed that the dorsalis pedis artery is kinked during foot dorsiflexion, whereas the distal posterior tibial artery is kinked during plantar flexion of the foot. CONCLUSION: BTA angioplasty for critical limb ischemia treatment is safe and feasible with satisfactory long-term results. BTA stent placement must be reserved for bailout indications.

Subintimal recanalization of occluded stents: the substent technique.

PURPOSE: Application of metal stents is complicated by neointimal hyperplasia leading to vessel restenosis and reocclusion. Treatment options in cases presenting with complete occlusion of the stented segment and recurrent critical limb ischemia (CLI) are limited. We present the option of the subintimal/substent technique in dealing with occluded stents. METHODS: The study included patients presenting with recurrent CLI due to impaired blood flow as a result of complete occlusion of previously inserted metal stents and unsuccessful intraluminal crossing of the lesion via either the antegrade or retrograde approach. In these cases, crossing the occlusion through the subintimal/substent plane was attempted. Primary end points included technical success, safety of the procedure, clinical improvement, and limb salvage, while secondary end points were patient survival, primary patency, and vessel restenosis rates at 1-year follow-up. Study end points were calculated by Kaplan-Meier survival analysis. RESULTS: Between July 2006 and October 2011, a total of 14 patients (mean age 69.14 ± 12.59 years, 12 men) were treated with the substent technique and included in the analysis. Technical success rate was 85.71% (12 of 14), with a total lesion length of 193.57 ± 90.78 mm. The mean occluded stented segment length was 90.21 ± 44.34 mm. In 10 (83.33%) of 12 cases, a new stent had to be placed by the side of the old occluded one, while the remaining two cases (16.67%) were treated only with balloon angioplasty. No serious adverse events were noted during the immediate postprocedural period. All successfully treated patients improved clinically. Estimated limb salvage was 90.9%, and patient survival rate was 90.0% at 1 year's follow-up. Primary patency was 45.50% and vessel restenosis 77.30%. CONCLUSION: Subintimal recanalization of occluded metal stents through the substent plane is a valuable alternative treatment option, especially in patients with recurrent CLI with few alternatives.

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.

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.

Transauricular embolization of the rabbit coronary artery for experimental myocardial infarction: comparison of a minimally invasive closed-chest model with open-chest surgery.

INTRODUCTION: To date, most animal studies of myocardial ischemia have used open-chest models with direct surgical coronary artery ligation. We aimed to develop a novel, percutaneous, minimally-invasive, closed-chest model of experimental myocardial infarction (EMI) in the New Zealand White rabbit and compare it with the standard open-chest surgical model in order to minimize local and systemic side-effects of major surgery. METHODS: New Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD) coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG), cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP) measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining. RESULTS: In total, 38 subjects underwent EMI with a surgical (n = 17) or endovascular (n = 21) approach. ST-segment elevation (1.90 ± 0.71 mm) occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68) within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05). Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68). CONCLUSION: The proposed model of transauricular coronary coil embolization avoids thoracotomy and major surgery and may be an equally reliable and reproducible platform for the experimental study of myocardial ischemia.

Below-the-knee drug-eluting stents and drug-coated balloons.

Endovascular procedures have evolved to the mainstream treatment of choice for revascularization of infrapopliteal obstructive disease, especially in patients suffering from critical limb ischemia and multiple comorbidities. However, standard balloon angioplasty is limited by the potential of a suboptimal acute outcome due to elastic recoil and/or flow-limiting dissection, followed by neointimal hyperplasia and progressive vascular restenosis even in the case of bare-metal stent use. Drug-eluting stents and drug-coated balloons are emerging endovascular technologies with the promise of significant inhibition of vessel restenosis and improved clinical outcomes. The current review outlines the drug-eluting properties of those instruments and summarizes the currently available clinical data. The authors critically appraise the current status and also provide a glimpse of the near future of endovascular below-the-knee treatments.

Subintimal angioplasty of long chronic total femoropopliteal occlusions: long-term outcomes, predictors of angiographic restenosis, and role of stenting.

PURPOSE: The purpose of this article is to report the results of a prospective single-center study analyzing the long-term clinical and angiographic outcomes of subintimal angioplasty (SIA) for the treatment of chronic total occlusions (CTOs) of the femoropopliteal artery. MATERIALS AND METHODS: Patients with severe intermittent claudication or critical limb ischemia (CLI) were enrolled in the study. All lesions were treated with SIA and provisional stenting. Primary end points were technical success, patient survival, limb salvage, lesion primary patency, angiographic binary restenosis (>50%), and target lesion revascularization (TLR). Regular clinical and angiographic follow-up was set at 6 and 12 months and yearly thereafter. Study end points were calculated with life-table survival analysis. Proportional-hazards regression analysis with a Cox-model was applied to adjust for confounding factors of heterogeneity. RESULTS: Between May 2004 and July 2009, 98 patients (105 limbs, patient age 69.3±9.9 years) were included in the study. Technical success rate was 91.4% with a lesion length of 121±77 mm. Limb-salvage and survival rates were 88.7% and 84.1% at 3 years, respectively. After 12, 24, and 36 months, primary patency was 80.1%, 42.3%, and 29.0%, angiographic binary restenosis was 37.2%, 68.6%, and 80.0%, and TLR was 84.8%, 73.0%, and 64.5%, respectively. CLI was the only adverse predictor for decreased primary patency (hazard ratio [HR] 0.36; 95% confidence interval [CI] 0.16-0.80, p=0.012), whereas significantly less restenosis was detected after spot stenting of the entry and/or re-entry site (HR 0.31; 95% CI 0.10-0.89, p=0.01 and HR 0.20; 95% CI 0.07-0.56, p=0.002, respectively). CONCLUSIONS: Subintimal angioplasty is a safe and effective revascularization technique for the treatment of CTOs of the femoropopliteal artery. Provisional stenting may have a role at the subintimal entry or true lumen re-entry site.