Panagiotis Kitrou

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.

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.

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.

Targeted True Lumen Re-Entry With the Outback Catheter Accuracy, Success, and Complications in 100 Peripheral Chronic Total Occlusions and Systematic Review of the Literature

Purpose: To report a single-center experience with the Outback re-entry device for targeted distal true lumen re-entry during subintimal recanalization of chronic total occlusions (CTOs) and compare the results with a systematic review of the literature. Methods: Between February 2011 and July 2013, 104 Outback devices were employed in 91 patients (mean age 64±9 years; 57 men) for subintimal recanalization of 100 vessels with CTOs after initial failure of spontaneous reentry. Fifty-two cases involved a retrograde approach to aortoiliac occlusions and 48 were re-entry attempts in infrainguinal CTOs. Outcome measures included complications and technical success, defined as successful targeted re-entry at the preplanned site of the distal true lumen. To evaluate device accuracy, the re-entry distance (between the point of true vessel reconstitution and the eventual re-entry point) was measured. Results: Outback success was 93% (93/100); only 7 cases failed owing to heavy calcification (5/52 aortoiliac vs 2/48 infrainguinal, p=0.44). Re-entry was highly accurate, with a re-entry distance of ~1 cm in both subgroups (1.2±0.1 cm in aortoiliac vs 1.3±0.1 cm in infrainguinal, p=0.40). There were no major and 17 minor complications (9/52 aortoiliac vs 8/48 infrainguinal, p=0.93). Results are in line with the systematic review that identified 11 studies (only 1 randomized trial) involving mostly the femoropopliteal segment (119 aortoiliac and 464 infrainguinal segments). The pooled Outback success rate was 90% (95% confidence interval 85% to 94%) and the pooled complication rate was 4.3% (95% confidence interval 1.6% to 8.3%). Conclusion: The Outback device is safe and has a very high rate of achieving targeted true lumen re-entry, which minimizes the sacrifice of healthy vessel in the aortoiliac and infrainguinal arteries.

Comparative Effectiveness of Plain Balloon Angioplasty, Bare Metal Stents, Drug-Coated Balloons, and Drug-Eluting Stents for the Treatment of Infrapopliteal Artery Disease Systematic Review and Bayesian Network Meta-analysis of Randomized Controlled Trials

Purpose: To report a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons (PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each other in the infrapopliteal arteries. Methods: Sixteen RCTs comprising 1805 patients with 1-year median follow-up were analyzed. Bayesian random effects binomial models were employed (WinBUGS). Relative treatment effects were expressed as odds ratios (ORs) with 95% credible intervals (CrI), and the cumulative rank probabilities were calculated to provide hierarchies of competing treatments. Quality of evidence (QoE) was assessed with the GRADE (grading of recommendations assessment, development, and evaluation) system. Sensitivity, heterogeneity, and consistency analyses were performed. Results: There was high QoE that infrapopliteal DES significantly reduced restenosis compared with BMS (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95% CrI 0.11 to 0.45). Likewise, DES significantly reduced target lesion revascularization (TLR) compared with BA (OR 0.41, 95% CrI 0.22 to 0.75) and BMS (OR 0.26, 95% CrI 0.15 to 0.45). Paclitaxel-coated balloons also reduced TLR compared with BA (OR 0.55, 95% CrI 0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18 to 0.67), but QoE was low to moderate. BA had lower TLR than BMS (OR 0.63, 95% CrI 0.40 to 0.99) with high QoE. DES was the only treatment that significantly reduced limb amputations compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB (OR 0.51, 95% CrI 0.26 to 0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with moderate to high QoE. DES also significantly improved wound healing compared with BA (OR 2.02, 95% CrI 1.01 to 4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with high QoE. Results were stable on sensitivity and meta-regression analyses without any significant publication bias or inconsistency. Conclusion: Infrapopliteal DES were associated with significantly lower rates of restenosis, TLR, and amputations and improved wound healing compared to BA and BMS. DES also significantly reduced amputations compared with PCB.

Evaluation of zotarolimus-eluting metal stent in animal ureters.

BACKGROUND AND PURPOSE Drug-eluting stents proved to minimize neointimal hyperplasia in coronary vessels. Hyperplastic reaction is the most common unwelcome event related to the use of metal mesh stents in the ureter. We evaluated the effect of zotarolimus-eluting stent (ZES) Endeavor Resolute in the porcine and rabbit ureter. MATERIALS AND METHODS A ZES and a bare metal stent (BMS) were inserted in each ureter of 10 pigs and 6 rabbits. The insertion was performed by the retrograde approach. CT was used for the evaluation of porcine ureters while intraoperative intravenous urography (IVU) was used for rabbit ureters. The follow-up included CT or IVU every week for the following 4 weeks for pigs and 8 weeks for rabbits. Renal scintigraphies were performed before stent insertion and during the third week in all animals. Optical coherence tomography (OCT) has been used for the evaluation of the luminal and intraluminal condition of the ureters with stents. Histopathologic examination of the these ureters embedded in glycol-methacrylate was performed. RESULTS Hyperplastic reaction was present in both stent types. BMSs in seven porcine ureters were completely obstructed while porcine ureters with ZES stents had hyperplastic tissue that did not result in obstruction. Two rabbit ureters with BMS stents were occluded while no ZES was associated with ureteral obstruction. The function of the seven porcine renal units and the two rabbit units with obstructed ureters with stents was compromised. The OCT revealed increased hyperplastic reaction in the ureters with BMS stents in comparison with those with ZESs. Although, hyperplastic reaction was present in all cases, pathologic examination revealed significantly more hyperplastic reaction in BMSs. CONCLUSION ZESs in the pig and rabbit ureter were not related to hyperplastic reaction resulting in stent occlusion. These stents were related to significantly lower hyperplastic reaction in comparison with BMSs while inflammation rates were similar for both stent types.

NGF Promotes Hemodynamic Recovery in a Rabbit Hindlimb Ischemic Model Through trkA- and VEGFR2-dependent Pathways

Abstract: 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 &mgr;m) 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.

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.

Cutting balloons, covered stents and paclitaxel-coated balloons for the treatment of dysfunctional dialysis access

ABSTRACT Introduction: Percutaneous transcatheter balloon angioplasty has evolved to the current mainstay treatment for salvage of dysfunctional dialysis access. Nonetheless, it is frequently associated with recurrent vessel restenosis and the need for multiple repeat treatments in order to maintain hemodynamic patency. Cutting-balloons, covered stents or stent-grafts, and paclitaxel-coated balloons have been extensively tested and investigated with the aim to improve immediate anatomical and long-term clinical results. Areas covered: In the present overview, we discuss the background and appraise relevant medical literature on the aforementioned technologies and provide a more in-depth synthesis of the results of different clinical studies for each device category. We will also discuss the limitations in the mode of action of each group of devices and envision what the future holds for the challenging field of dialysis access interventions. Expert commentary: We propose a good practice algorithm for the treatment of thrombosed or dysfunctional dialysis access.