The Gold Standard. ASDIN 2014 Scientific Meeting. When is an AVF mature? Longitudinal Assessment of AVF Maturation with Ultrasound.

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Wen is an AVF mature? Longitudinal Assessment of AVF Maturation wit Ultrasound CONFLICT of INTEREST DECLARATION St Micael s Hospital olds patent on use of ig frequency probes for evaluation of venous structures American Society of Diagnostic and Interventional Neprology February 2014 Dr. S. Donnelly Objectives To review te emodynamic principles of vascular remodeling Morbidity- AVF Vs. PTFE Grafts 2-7 Te Gold Standard Frequency of stenosis Frequency of trombosis Monitoring remodeling wit HFUS Defining Good to keep going Defining Good to go Frequency of infection Financial costs Higer primary patency rates Mortality- AVF Vs. Cateters/Grafts 8 Central venous cateters: Arterio-venous grafts: 50% mortality 26% mortality 3 2. National Kidney Foundation. Am J Kidney Dis 3.2001. 3. Pisoni RL et al. Vascular access use in Europe and te United States: Results from te DOPPS. Kidney Int 61.2002. 4. Woods JD et al. Vascular access survival among incident emodialysis patients in te United States. Am J Kidney Dis 30.1997 5. Curcill DN et al. Canadian emodialysis morbidity study. Am J Kidney Dis 19.1992 6. Dingra RK et al. Type of Vascular access and mortality in U.S. emodialysis patients. Kidney Int 60. 2001. 7. Lee H et al. Cost analysis of ongoing care of patients wit ESRD: te impact of daily modality and dialysis access. Am J Kidney Dis 40. 2002. 8. Astor BC et al., Type of vascular access and survival among incident emodialysis patients: CHOICE study, J AM Soc Neprol 16.2005 Importance of Successful Cannulation Endotelial side of excised fistula Eac puncture Vessel injury 3x/week treatments ~ 312 punctures/annum

Te emodynamic principles of vascular remodeling Hemodynamic Considerations 1. Te pysiologic and biomecanical underpinnings of vascular remodeling 2. A quantitative definition of cannulation readiness Sear Stress (flow issue) Hoop Stress (pressure issue) Sear Stress At a mecanical level, vessels try to maintain teir original level of stress. Sear stress (τ ) for Poiseuille flow (steady laminar flow in a cylindrical vessel) is given by: = 4 μ Q π R 3 Were: μ = viscosity Q = volumetric flow rate R = vessel radius Sear Stress Homeostasis Hoop Stress R r v outflow vein dilatation Terefore: = 4 μ Q π R 3 τ α Q / R 3 Te circumferential (oop) stress (σ) in a cylindrical vessel can be approximated by a modification to Laplace s Law: Were: P = pressure R = vessel radius = wall tickness If Q increases by x times, R must increase by x 1/3 times

Hoop Stress Homeostasis Hoop Stress Homeostasis σ α R / Terefore: If R increases by x must increase by x σ α R / Terefore: If R increases by x must increase by x Hoop Stress Homeostasis Hemodynamic Considerations Summary σ α outflow R / vein ypertropy Terefore: If R increases by x must increase by x Sear Stress- flow issue Sear Stress Homeostasis - dilatation Hoop Stress - pressure issue Hoop Stress Homeostasis - ypertropy At a mecanical level, vessels try to maintain teir original level of sear stress. if tey can. Access to Science in Hemodialysis Objectives To review te emodynamic principles of vascular remodeling BUT sometimes a vessel cannot remodel normally due to oter factors (diabetes, aterosclerosis, genetics, venipuncture trauma ) Defining Good to keep going 18

Hemodynamic Considerations Applied Criteria for fistula maturation are clinical and quasi qualitative Maturation Failure AVF maturation failure ranges between 28-53% 9 Etiology: So. How do we know if te fistula maturation is on track? Diminised arterial flow 10 Venous trombosis and occlusion 11 Venous negative remodeling Periperal and central venous stenosis 12 9. Asif A et al. Early Arteriovenous Fistula Failure: A Logical Proposal For Wen and How to Intervene. Clin J Am Soc Neprol. 1. 2006. 10. Lok CE et al. Overcoming barriers to arteriovenous fistula creation and use. Semin Dial 16. 2003. 11. Hayasi R et al. Vascular access for emodialysis. Nat Clin Pract Neprol 2.. 2006. 12. Besarab A, et al. Utility of intra-access pressure monitoring in detecting and correcting venous outlet stenoses prior to trombosis. Kidney Int 47. 1995. Hemodynamic Considerations So. How do we know if te fistula maturation is on track? Good to keep going Sear Stress (flow issue) Hoop Stress (pressure issue)

Study Design-Observational Metods Jaberi et al. Radiology 261(2):616-624, 2011 Longitudinal Cannulation readiness was operationalized as no extravasation during te dialysis treatment at 200-250 ml/min blood pump speeds Blood viscosity (μ) was approximated using a multivariate model proposed by Eckmann et al. 13 Mean arterial blood pressure was used to calculate oop stress (σ). Statistical Analysis: Evaluation of Clinical parameters: DOPPS criteria for demograpic, clinical and laboratory parameters. Human subject approval by St. Micael s Hospital (Toronto, Canada) Researc Etics Board Statistical analysis was performed wit SPSS v11.0.1 (SPSS Inc., Cicago, IL USA). Absolute agreement between independent observers was evaluated using Reliability Analysis wit alpa scale and interclass correlation (ICC). 13. Eckmann DM et al. Hematocrit, volume expander, temperature, and sear rate effects on blood viscosity. Anest Analg 9. 2000. Image Measurement Jaberi et al. Radiology 261(2):616-624, 2011 Image Measurement Jaberi et al. Radiology 261(2):616-624, 2011 Hig Frequency Ultra-sound Probe (VisualSonics Inc., Toronto, Canada) Vevo 708 55 MHz Vevo 704 40 MHz Focal Lengt 4.5 mm Focal Lengt 6.0 mm Measurements by 3 blinded independent observers (2 radiologists, 1 vascular access nurse) completed offline. Te anterior wall tickness was measured in longitudinal section at 5cm, 10cm, and 15cm above te anastomosis. Te venous internal diameter and volume flow rate (Pilips IU 22, 9-3MHz probe ) were measured in transverse section at te above sites. 4 μ Q = π R 3 Week 1 (5cm) Week 4 (5 cm) New Fistula: 0.09mm Fistula pre-primed : 0.19 mm New Fistula: 0.16 mm Fistula pre-primed : 0.19mm

Week 20 (5 cm) Venous Diameter New Fistula: 0.22mm Fistula pre-primed: 35mm Venous Diameter Wall Tickness i) Overall increase as expected. ii) Te initial slope of increase appears to be iger; greater disruption of emodynamics iii)? cubic regression. Wat appens between 8-16 weeks? 33 Hoop Stress Homeostasis Hoop Stress σ α R / Terefore: If R increases by x must increase by x

Hoop Stress Sear Stress i) Increases and ten stabilizes to almost baseline levels ii) vascular remodeling resulting in omeostasis. Sear stress (τ ) for Poiseuille flow (steady laminar flow in a cylindrical vessel) is given by: = 4 μ Q π R 3 Were: μ = viscosity Q = volumetric flow rate R = vessel radius 37 Sear Stress Sear Stress i) Overall decrease ii) likely secondary to remodeling iii)? explain plateau 40 Longitudinal Study Significance of Researc Same Subject- 5 cm from Anastomosis Te decisions to ligate collateral vessels can be informed wit clearly identified expected outcomes. Pre-Op Week 6 Week 20 Furter, te readiness of te fistula or maturation point can be more clearly defined and obviate te trial and error approac to te first cannulation tat describes current practice.

Summary & Conclusions Maturation Process Simplified description of te process: Good to keep Going: Tracking maturation process may be enanced by following venous wall tickness. i) inflow arterial dilatation ii) outflow venous dilatation iii) outflow venous tunica media ypertropy Vascular remodeling leading to increased vessel integrity to support dialysis: i) blood flow >600 ml/min ii) >0.6 cm venous diameter iii) 0.6 cm below te skin surface iv) witstand repeated cannulation Summary Vascular remodeling return to omeostasis Vascular remodeling imaging wit HFUS Defines good progress or? trigger to intervene Defines cannulation readiness Neprology Researc Office St. Micael s Hospital Acknowledgments 45