Balloon Angioplasty for Low Flow Access Dheeraj K. Rajan MD, FRCPC, FSIR Division of Vascular and Interventional Radiology University of Toronto – University Health Network

Angioplasty – The Gold Standard Goal is to relieve the stenosis Venous stenoses associated with dialysis access is typically unyielding often requiring high pressure balloons Following PTA, recurs in a short period of time Complications of PTA

Patch Angioplasty is Surgery Balloon versus patch angioplasty as an adjuvant Tx to surgical thrombectomy of hemodialysis grafts. Case control study of PTA and patch angioplasty pts RESULTS: 10 patencies of patch & PTA group: 86% vs 77% at 1 mo, 45% vs 40% at 3 mos, 17% vs 28% at 6 mos No statistically signif diff btw the 2 groups CONCLUSION: Balloon angioplasty offers advantages to patch angioplasty, with similar patency rates. We recommend balloon angioplasty as a comparable method to salvage dialysis access grafts DOQI guideline  percutaneous Bitar G et al. Am J Surg 1997;174:140-2. Slide courtesy of Ziv Haskal

Angioplasty The potential long-term patency rate following PTA is (possibly) well established. Published series consistently report 40% to 50% 6-month unassisted patency rates from PTA. Long-term unassisted patency after surgical revision is less well established due to reporting of cumulative patency.

Prospective 38-63% 6 mo. (retrospective series) Probably more accurate AVG 10 Patency after PTA 38-63% 6 mo. (retrospective series) Probably more accurate 23-41% 6mo. (prospective series) 5 5

Levels of evidence: Access Interventions Slide courtesy Ziv Haskal

Advances – What Advances? K/DOQI recommends 50% 6 month primary patency following angioplasty Technical success <30% residual stenosis New devices – do they improve patency? Is there any value in prophylactic intervention? The future?

PTA Resistant Stenoses Lesions resistant to PTA overall 10-15% Clark, JVIR 2002; 51 Rajan, Radiology 2004; 508 55% of dialysis stenoses required inflation pressures > 15 atm when grafts/fistulas were combined Trerotola, JVIR 2005; 1613. Lesion most difficult to treat is the cephalic arch

Patencies Lay JP et al. Clin Radiol 1998; 53:608-611. Clark TW et al. J Vasc Interv Radiol 2002; 13:51-59. Manninen HI et al. Radiology 2001; 218:711-718. Turmel-Rodrigues et al. Nephro Dial Transplant 2000; 15:2029-2036

What else has been tried?

Conquest versus regular PTA Grafts 55 PTA’s each group No difference in patency Only venous anastomosis grafts 10-20% stenoses require pressure >15 atm

Cutting Balloon Folding Design Slow inflation & deflation 1ATM every 3-5 sec. Atherotomes descend within the folds of balloon material Minimizes atherotome exposure to healthy tissue Device should not exceed 10 inflation /deflation cycles The folding design of the balloon has been manufactured to minimize exposure of the atherotome to healthy tissue. A slow inflation technique of 1 ATM every 3-5 seconds aids in the atherotome’s descent into the folds of the balloon material. While the Peripheral Cutting Balloon can be used for multiple inflations, it is not recommended to exceed 10 cycles for each device.

Cutting Balloon

JVS -2014 623 patients – mixed grafts and fistulas At venous anastomosis at 6 and 12 months primary assisted patency significantly better 86 vs 63; 56 vs 37% Really treatment area primary patency Not access circuit or secondary Ultrasound follow-up monthly

Cutting Balloon - Again Autogenous fistulas USED if conventional PTA did not work 71/516 randomized to HPTA vs. cPTA Six month f/u angio 66% versus 40% at 6 months JVIR 2014; 190

Nitinol Stents Since 1991, >10% of PTA procedures associated with stent placement Chan 2008 25% versus 3% primary patency 6 mts AVG’s Retrospective with 64 patients Centrally: 14.9 months 12 month: 67% Mean primary patency peripheral: 8.9 months 12 month: 20% Almost all were severely stenosed at 6 mts Vogel, JVIR 2004: p1051-1060

Kariya S, et al. Cardiovasc Intervent Radiol (2009) 32:960–966 39% 6-month 10 patency for stents 73% 6-month 10 patency for PTA p = 0.028 Kariya S, et al. Cardiovasc Intervent Radiol (2009) 32:960–966

Stent Usage No definite conferred long term benefit over PTA Can convert focal lesion to lesion length of the stent Used as bailout for: Rupture Reobtruction Recoil ? rapid recurrence of stenosis (<3 mts K/DOQI)

Novel Technologies Cryotherapy Gene therapy Drug eluding stents Brachytherapy Atherectomy catheters Dissolving stents

Brachytherapy cont… Dosing scheme: 18.4 Gray at 0.5mm into the vein wall Treatment times: 214 to 323 seconds

Brachytherapy Novoste Bravo trial Beta radiation source Trial cancelled Switched study population inclusion criteria part way through trial 42% target lesion primary patency end point at 6 months as compared to 0% of the control group (P = 0.015) - did not translate into an improvement in secondary patency at either 6 or 12 months. Misra S, KI 2006 (70) p 2006

Cryoplasty PolarCath System Nitrous Oxide Coolant

Cryoplasty Stenosis or thrombosis increased from 3 weeks to 16 weeks Only 5 patients Am J Kidney Dis, 2005; 45(2): e27-32. 20 patients 35% technical success 25% 6 month patency Associated with severe pain Gray JVIR 2008

Atherectomy Devices Atherectomy SilverHawk/TurboHawk/DiamondBack T – Designed to cut through CTO’s (hard plaque) S – Everyday plaque with no thrombus and/or calcified plaques No iliac indication; for above/below knee Preserves treatment options Atherectomy Limited studies – three 5/13 (38%) patent at 6 mts largest study expensive

Bioabsorbable Stents Constructed of polylactic acid Two layers : anti-proliferation drug that absorbs and second is made of a harder crystalline matrix of PLA which dissolves in two years Biodegradable magnesium alloy dissolves in months Also a vehicle for delivery of nanoparticles

Drug Eluding Balloons Targeted delivery of drugs to vascular wall or perivascular region Antigrowth factors Angiogenesis factors Gene therapy Injection of cells Local delivery concentrations can be 500x greater than systemic therapy

Drug Eluding Balloons InPact Admiral Balloon (paclitaxil) 40 patients (only AVF’s) randomized 1:1 No defined prospective F/U TLR-free survival was significantly superior in the PCB group 308 d vs 161 d. However, device success rates were 100% in the HPB group and 35% in the PCB group JVIR 2015 – in press

Drug Eluding Balloons Adventitial delivery 130 micron needle Controlled localized delivery Reduced toxicity

Drug Eluding Balloons Questions to be answered Drug dose Pre PTA or Post PTA Duration of dwell time

Question Should be PTA versus Stent Garfts No definite evidence that proves stents are better than angioplasty for patency for peripheral and central lesions Stents do improve technical success with some evidence of improved effect (Vogel, JVIR 2005) Early randomized studies demonstrate clear patency advantage of stent grafts

Slide courtesy Bart Dolmatch Self-expanding ePTFE Covered Stents Viabahn Flair Viatorr Fluency Slide courtesy Bart Dolmatch

N Engl J Med 2010;362(6):494-503 (Core Lab Analysis)

FLAIR study Survival Free from Treatment Area Primary Patency Failure Log-Rank p=0.003 Wilcoxon p=0.008 FLAIR study 41 41

Of course, this is achievable with PTA, isn’t it? 2 mos 29 mos s berman AVG functions 5 years after placement.

Revise Trial Presented at SIR Gore Viabahn device for venous anastomotic stenosis Six month primary patency significantly different Secondary patency the same Renova 12-month ACPP for the stent graft group was significantly better than the PTA group, 24.1% vs. 10.3% (p=0.005), respectively.

Literature (Cephalic Arch) Randomized Study Stent versus stent graft 25 patients Six month primary patency was 82% in the stent graft group and 39% in the bare stent group. One-year primary patency was 32% in the stent graft group and 0% in the bare stent group Historical PTA 42% and stent 39% (Rajan vs. Shemesh) Shemesh, JVS 2008 48(6): 1524-1531

Another Study: 14 patients mature brachiocephalic fistulas. Five were randomized to angioplasty (PTA) and 9 to stent grafting. Technical success 100% Mean patency in PTA group 100 days (56-154 days) vs 300 days (201-504 days) for SG Primary access circuit patency at 6 and 12 months: PTA: 0% Stent graft: 67 and 22% (95% CI: 42-100; 6-75) p<0.01 Primacy target lesion patency at 3, 6 and 12 months PTA: 60% (CI 29-100%), 0% and 0% SG: 100%, 100% and 29% (CI: 9-93%) (p<0.01)

Surgical Intervention Anatomic bypasses Turn down cephalic vein to basilic or axillary vein Autologous or artificial bypass Patch Skilled motivated surgeons needed Literature Not much short, medium or long term data published

Literature Transposition of cephalic vein to axillary or basilic vein 13 Patients Six month primary patency rate of angioplasty before the surgical revision of 8% Six month primary patency rate following surgical revision of 69% at 6 months. However: Why was PTA 8% so much lower than other studies Surgical revision is technically creating a new access No length of follow-up provided or standard error limiting interpretation of data What about damage to axillary and basilic veins in the future? Kian, Sem Dialysis 2008: 21(1): 93-6.

AVF Stent Grafts 17 patients Thromboses, stenoses, pseudoaneurysms Access circuit patency: 88% at 6 and 12 months Lesion patency: 94% at 6 and 12 months Bent CL, JVIR April 2010

Why Does Most Stuff Not Work? Intimal injury leading to intimal hyperplasia Have to inhibit or prevent injury, exclude injured area Most devices repeat or create injury cycle Surgery itself associated with injury cycle Poor reporting/study design Mixing of grafts/fistulas/lesion types Type of follow-up definitions

Summary No evidence to date to suggest any new devices / methods improve overall access patency compared to angioplasty for venous stenosis in hemodialysis patients Stents should be used for salvage only, not primary intervention Stent grafts have improved patency in graft patients – does this translate to fistulas?