Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS: This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Thoracic Endovascular Aneurysm Sealing of a Complex Thoracoabdominal Aneurysm.

PURPOSE: To report bailout treatment of a thoracoabdominal aortic aneurysm using a single Nellix stent and parallel stents. CASE REPORT: A 74-year-old man with multiple comorbidities and a previous fenestrated Anaconda stent-graft for a 60-mm juxtarenal aneurysm was diagnosed with a type IV thoracoabdominal aneurysm on the 2-year computed tomography angiography (CTA) scans. The imaging showed >10-mm downward migration of the proximal Anaconda stent with a massive type Ia endoleak and aneurysmal evolution of the distal descending thoracic aorta; the superior mesenteric artery (SMA) and renal artery covered stents were patent and intact. Open conversion or a second custom-made endograft was not feasible. A plan was devised to use off-the-shelf materials, including the deployment of a single Nellix stent extending from the descending thoracic aorta into the stented area of the fenestrated endograft, with parallel chimney stent-grafts into the SMA and right renal artery; the left renal artery was treated with a bare stent in a periscope configuration. Transient paraparesis was resolved with cerebrospinal fluid drainage. At 6-month CTA, ongoing aneurysm exclusion with patent SMA and renal arteries was confirmed. CONCLUSION: Thoracic endovascular aneurysm sealing with visceral and renal stenting seems to be a feasible bailout alternative treatment for urgent, complex cases without reconstruction options.

Paclitaxel-Eluting Balloon vs Standard Angioplasty to Reduce Restenosis in Diabetic Patients With In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Arteries: Three-Year Results of the DEBATE-ISR Study.

PURPOSE: To report the 3-year safety and effectiveness outcomes from the prospective all-comers DEBATE-ISR study (ClinicalTrials.gov identifier NCT01558531) of symptomatic diabetic patients with femoropopliteal in-stent restenosis (ISR) undergoing treatment with paclitaxel-eluting balloons compared with historical diabetic controls. METHODS: From January 2010 to December 2011, 44 consecutive diabetic patients (mean age 74±11 years; 32 men) were treated with drug-eluting balloons (DEBs) and enrolled in the study. The control group comprised 42 consecutive diabetic patients (age 76±7 years; 23 men) treated with conventional balloon angioplasty (BA) from 2008 to 2009. RESULTS: No significant differences in terms of clinical, angiographic, or procedural characteristics were observed between the study groups. Critical limb ischemia was present in the majority of patients. Tosaka class III ISR was observed in more than half of the patients. Mean lesion length was 132±86 and 137±82 mm in the DEB and BA groups, respectively (p=0.7). At 3-year follow-up, the rate of target lesion revascularization (TLR) was 40% in the DEB group vs 43% in the BA group (p=0.8); Kaplan-Meier analysis showed no significant differences in terms of freedom from TLR. The presence of a Tosaka class III occlusion was associated with a worse outcome in both study groups (odds ratio 3.96, 95% confidence interval 1.55 to 10.1, p=0.004). CONCLUSION: Using DEBs for femoropopliteal ISR yielded similar results to BA in terms of TLR at 3-year follow-up. The treatment of more complex ISR lesions was associated with an increased rate of TLR, irrespective of the technology used.

Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.

PURPOSE: To test the ability of a drug-eluting balloon (DEB) to reduce recurrent in-stent restenosis (ISR) in diabetic patients with femoropopliteal stents. METHODS: A prospective all-comers study [Drug-Eluting Balloon in Peripheral Intervention for In-Stent Restenosis (DEBATE-ISR); ClinicalTrials.gov identifier NCT01558531] of symptomatic diabetic patients with femoropopliteal ISR undergoing treatment with paclitaxel-eluting balloons was designed to compare their 12-month recurrent restenosis rate with that of historical diabetic controls. From January 2010 to December 2011, 44 consecutive diabetic patients (32 men; mean age 74±11 years) were treated with DEBs and enrolled in the study. The control group comprised 42 diabetic patients (23 men; mean age 76±7 years) treated with a conventional balloon for femoropopliteal ISR from 2008 to 2009. RESULTS: No significant differences in terms of clinical, angiographic, or procedural characteristics were observed between the study groups. Lesion length was 132±86 mm in the DEB group vs. 137±82 mm in the BA group. Procedural success, defined as a residual stenosis <30% in the restenotic segment (stent +5 mm at proximal and distal edges), was obtained in all treated lesions. At 1-year follow-up, 6 patients died (3 in each group), and 1 patient in the BA group underwent major amputation. Recurrent restenosis, assessed by angiography (66%) or ultrasound (34%), occurred in 8/41 (19.5%) patients in the DEB group vs. 28/39 (71.8%) in the BA group (p<0.001). Target lesion revascularization for symptomatic recurrent restenosis was performed in 6/44 (13.6%) patients in the DEB vs.13/42 (31.0%) in the BA group (p=0.045). CONCLUSION: Using DEB for treating femoropopliteal ISR led to a significant reduction in recurrent restenosis and repeat angioplasty at 1-year follow-up as compared to historical controls.

Drug-eluting balloon in peripheral intervention for the superficial femoral artery: the DEBATE-SFA randomized trial (drug eluting balloon in peripheral intervention for the superficial femoral artery).

OBJECTIVES: This study sought to compare paclitaxel-eluting balloon (PEB) with conventional percutaneous transluminal angioplasty (PTA), followed by systematic implantation of a self-expanding nitinol bare-metal stent (BMS) in patients at risk for restenosis. BACKGROUND: PTA is an effective strategy for treating atherosclerosis of the femoropopliteal axis (FPA). Whereas PEB have shown advantage over uncoated balloons in the treatment of simple lesions, it is unknown whether these results are applicable to complex degrees of FPA atheroma. METHODS: A total of 104 patients (110 FPA lesions in 110 limbs) were randomly assigned to either PEB + BMS or PTA + BMS. The primary endpoint was 12-month binary restenosis. Secondary endpoints were freedom from target lesion revascularization and major amputation. Post hoc subanalyses were performed for the comparison of long (≥100 mm) versus short lesions and true lumen versus subintimal approach. RESULTS: Mean lesion length was 94 ± 60 versus 96 ± 69 mm in the PEB + BMS and PTA + BMS groups (p = 0.8), respectively. The primary endpoint occurred in 9 (17%) versus 26 (47.3%) of lesions in the PEB + BMS and PTA + BMS groups (p = 0.008), respectively. A near-significant (p = 0.07) 1-year freedom from target lesion revascularization advantage was observed in the PEB + BMS group. No major amputation occurred. No significant difference was observed according to lesion characteristics or technical approach. CONCLUSIONS: Pre-dilation with PEB angioplasty prior to BMS implantation, as compared to PTA + BMS in complex FPA lesions, reduces restenosis and target lesion revascularization at 12-month follow-up. Restenosis reduction is maintained irrespective of lesion length and recanalization technique. (Drug Eluting Balloon in Peripheral Intervention for the Superficial Femoral Artery [DEBATE-SFA]; NCT01556542).

Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia.

BACKGROUND: The 1-year restenosis rate after balloon angioplasty of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries. METHODS AND RESULTS: The Drug-Eluting Balloon in Peripheral Intervention for below the knee angioplasty evaluation (DEBATE-BTK) is a randomized, open-label, single-center study comparing drug-eluting balloons and PTA. Inclusion criteria were diabetes mellitus, critical limb ischemia (Rutherford class 4 or higher), significant stenosis or occlusion >40 mm of at least 1 below-the-knee vessel with distal runoff, and life expectancy >1 year. Binary in-segment restenosis at a 1-year angiographic or ultrasonographic follow-up was the primary end point. Clinically driven target lesion revascularization, major amputation, and target vessel occlusion were the secondary end points. One hundred thirty-two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83 mm in the drug-eluting balloon group compared with 131±79 mm in the PTA group (P=0.7). Binary restenosis, assessed by angiography in >90% of patients, occurred in 20 of 74 lesions (27%) in the drug-eluting balloon group compared with 55 of 74 lesions (74%) in the PTA group (P<0.001); target lesion revascularization, in 12 (18%) versus 29 (43%; P=0.002); and target vessel occlusion, in 12 (17%) versus 41 (55%; P<0.001). Only 1 major amputation occurred, in the PTA group (P=0.9). CONCLUSIONS: Drug-eluting balloons compared with PTA strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of below-the-knee lesions in diabetic patients with critical limb ischemia.

Transrenal E-XL stenting to resolve or prevent type Ia endoleak in the case of severe neck angulation during endovascular abdominal aortic aneurysm repair.

During endovascular abdominal aortic aneurysm repair, a severely angulated neck can make proximal sealing of endografts challenging, and the occurrence of a type Ia endoleak can complicate the procedure. We describe an original adjunctive procedure involving transrenal placement of a self-expanding nitinol stent (E-XL aortic stent; Jotec GmbH, Hechingen, Germany) to remodel the proximal aortic neck and treat or prevent type Ia endoleaks in the case of severe angulation of the proximal neck.

Impact of critical limb ischemia on long-term cardiac mortality in diabetic patients undergoing percutaneous coronary revascularization.

OBJECTIVE: Development of critical limb ischemia (CLI) has been reported as an independent predictor of cardiac mortality in diabetic patients. We aimed to determine whether CLI, managed in a structured setting of close collaboration between different vascular specialists and treated with early endovascular intervention, has any impact on long-term cardiac mortality of diabetic patients initially presenting with symptomatic coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: We designed a prospective observational study of 764 consecutive diabetic patients undergoing percutaneous coronary intervention (PCI) in whom development of CLI was assessed by a dedicated diabetic foot clinic. Cardiac mortality at 4-year follow-up was the primary end point of the study. RESULTS: Among the 764 patients, 111 (14%) developed CLI (PCI-CLI group) and underwent revascularization of 145 limbs, with procedural success in 140 (96%). PCI-CLI patients at baseline had lower left ventricular ejection fraction (51 ± 11% vs. 53 ± 10%, P = 0.008), higher prevalence of dialysis (7% vs. 0.3%, P < 0.0001), and longer diabetes duration (13 ± 8 vs. 11 ± 7 years, P = 0.02) compared with PCI-only patients. At 4-year follow-up, cardiac mortality occurred in 10 (9%) PCI-CLI patients vs. 42 (6%) PCI-only patients (P = 0.2). Time-dependent Cox regression model for cardiac death revealed that CLI was not associated with an increased risk of cardiac mortality (hazard ratio 1.08 [95% CI 0.89-3.85]; P = 0.1). CONCLUSIONS: The development of promptly assessed and aggressively treated CLI was not significantly associated with increased risk of long-term cardiac mortality in diabetic patients initially presenting with symptomatic CAD.

Drug-eluting balloon angioplasty for carotid in-stent restenosis.

PURPOSE: To report midterm results of 3 cases in which drug-eluting balloons (DEBs) were successfully used for the management of carotid in-stent restenosis (ISR). CASE REPORT: Two women aged 68 and 70 years and a 68-year-old man were referred to our institution for asymptomatic severe stenosis [>80% with peak systolic velocity (PSV) >300 cm/s by Doppler ultrasound assessment] of individual Carotid Wallstents implanted in the proximal left internal carotid artery (ICA). In the angiosuite, the left ICA was engaged in a telescopic fashion with a triple coaxial system formed by a 6-F long sheath and a preloaded 5-F, 125-cm diagnostic catheter over a 0.035-inch soft hydrophilic guidewire. Under distal filter protection, the lesions were predilated using a 3.5 × 20-mm coronary balloon and then treated with two 1-minute inflations of a 4 × 40-mm Amphirion In.Pact paclitaxel-eluting balloon, followed by 3 months of dual antiplatelet therapy. At 12, 22, and 36 months, respectively, the patients are still asymptomatic, with duplex-documented stent patency at 6, 12, and 24 months, respectively. CONCLUSION: DEBs are an emerging strategy for carotid ISR, with encouraging midterm results in these patients. Further experience in larger cohorts is needed to confirm these preliminary observations.

A tailored approach to overcoming challenges of a bovine aortic arch during left internal carotid artery stenting.

PURPOSE: To investigate the efficacy and safety of a tailored approach to fit access and engagement techniques to the individual arch anatomy in patients with bovine-type aortic arch (BTAA) to overcome the perceived increased risk of technical failure and cerebral embolization during left internal carotid artery (LICA) stenting. METHODS: Thirty-five high surgical risk patients (23 men; mean age 68.6 years, range 62-90) with BTAA and LICA stenosis underwent carotid artery stenting (CAS). Left common carotid artery (LCCA) engagement was achieved by means of different techniques according to the configuration of the BTAA, arch type (I, II, or III), and angle between the innominate artery and the LCCA. The clinical, anatomical, and procedural data were retrieved from a prospectively maintained database and analyzed retrospectively to identify technical modifications required during the procedure compared with planning. RESULTS: The technical success rate was 100%. Transfemoral access was used in 21 (60%) cases. In this group, the soft engagement technique with hockey stick (HS) guiding catheter and buddy wire in the external carotid artery (ECA) was used in 13 (62%) cases, a simple telescopic technique with 6-F armed introducer or 7-F 40° guiding catheter in 5 (24%) cases, and a sequential technique with a MOMA proximal protection system in the remaining 3 (14%) cases. Among the 14 (40%) right brachial access cases, the telescopic technique with 6-F armed introducer was used in 13 cases. The remaining case was the only one in which the planned technique was changed (from the telescopic to sequential technique with ECA wire exchange). There were no intraprocedural or 30-day neurological events. CONCLUSION: An appropriate tailored interventional strategy, planned by means of preprocedural recognition of bovine arch anatomy, is associated with satisfactory safety and good success.

[Clinical outcome of percutaneous revascularization by stent-assisted balloon angioplasty of femoro-popliteal and tibial vessels in diabetic patients with critical limb ischemia]. / Efficacia clinica del trattamento percutaneo mediante angioplastica e provisional stenting dei vasi femorali, poplitei e tibiali in pazienti diabetici con ischemia critica dell'arto.

BACKGROUND: The aim of this study was to assess the long-term clinical outcome of percutaneous peripheral interventions in diabetic patients with critical limb ischemia (CLI) in terms of occurrence of major amputation and mortality. METHODS: From January 2004 to December 2007, all diabetic patients undergoing peripheral angiography and percutaneous revascularization for the presence of CLI were enrolled in this registry and followed prospectively. Limb salvage, mortality, and repeat revascularization were reported at long term. RESULTS: 267 diabetic patients (mean age 72.2 +/- 9.6 years) with 290 ischemic limbs represent the study population. Hypertension was present in 227 patients (85%), hypercholesterolemia in 85 (32%), chronic renal failure in 61 (23%). Ischemic heart disease was present in 80 patients (30%), carotid disease in 75 (28%). According to the Texas Diabetic Ulcers Classification, 203 patients (70%) had type CIII lesion, 29 (10%) CII, 9 (3%) CI, 20 (7%) DIII, 23 (8%) DII, and 6 (2%) DI; 440 lesions (169 tibial arteries, 261 femoro-popliteal arteries, and 10 iliac arteries) were dilated with stent implantation in 290 of them (66%). The procedure was successful in 415 (94%) with restoration of direct flow in at least one tibial artery. The ankle-brachial index was 0.32 +/- 0.11 before procedure and increased to 0.77 +/- 0.23 (p<0.001). One patient died suddenly during hospital stay. Mean follow-up length was 17 +/- 11 months. Of the 290 limbs, major amputation was necessary in 17 (6%) of which 10 had an unsuccessful procedure. Amputation was fatal in 7 cases (41%). Complete foot lesion healing was obtained in 238 (82%) and partial healing in 35 (12%). Death occurred in 42 patients (16%) and it was related to cardiac events in 16 (6%), cerebrovascular events in 8 (3%), acute renal failure in 8 (3%), and cancer in 10 (4%). Repeat revascularization occurred in 67 patients (23%) in the target limb and in 29 (11%) in the contralateral limb. CONCLUSIONS: Peripheral angioplasty with stent implantation is an effective procedure for limb salvage in diabetic patients with CLI. The high mortality is probably related to the systemic atherosclerosis process with involvement of coronary and cerebral circulation that leads to heart and cerebral fatal ischemic events.