Debate on Balloon Assisted Maturation The Biology is Wrong: BAM Won t Work BAM Dr. Rapp Debate BIVF Dr. Lawson Jeffrey H. Lawson, M.D., Ph.D. Departments of Surgery and Pathology Duke University Medical Center Durham, North Carolina VS. Fistula BAM vs. No BAM Failing Fistula Judgment Thoughtful vs. Dogmatic BAM No BAM 1
BAM vs. No BAM Algorithms vs. People What Debate? I will play the fool you will have me play -W. Shakespeare Success Fistulas Failure Major mode of Fistula failure Venous Stenosis Early Fistula Failure Small artery (<1.5 2mm) and small vein (<2 2.5 mm) Surgical manipulation Venipunctures Accessory veins Genetic predisposition As many as 60% of US fistulas fail to mature Late Fistula Failure Hemodynamic stress at the artery-vein anastomosis o Low shear stress o Turbulence o Compliance mismatch between artery and vein Venipunctures Angioplasty Uremia 2
Venous Stenosis smooth muscle cells Outflow Vein Proliferation Endothelial Progenitor Cells Endothelial Injury Myofibroblasts Bone marrow derived Neointimal cells Proliferation occurs from a cascade of events Mitogen-activated protein (MAP) kinase family plays a key role p42, p44 (ERK-1 and -2) ras dependent activation of p42/p44 leads to VSM proliferation Two classes of proteins can lead to MAP signaling in cells Tyrosine kinase receptors G protein coupled receptors Native Vein? Stenosis Fistula Biology Can we influence the path? Maturing Angioplasty Severe Stenosis??? Mature Occluded 3
What does Venous Angioplasty do? 1. Makes us feel better? 2. Makes the patient feel better? 3. Provides durable treatment to a diseased vessel? 4. Injures the vein it s trying to help? 5. Helps support our practice and the companies that make balloons? Endothelium Immediately Post Angioplasty Here shown is perivascular bleeding and denudation of the endothelium. 14 days later After 14 days, extensive cellular proliferation and thrombosis are apparent in the lumen. 4
The Surface of a Dysfunctional Endothelial Cell Temporal changes in CECs Following Angioplasty Angioplasty Cath only Endothelial dysfunction is characterized by the overexpression of leukocyte adhesion molecules (LAM), which serve to "capture" circulating leukocytes. These LAMs include intercellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), and the family of selectins including E- and P-selectins. Boos, C. J. et al. Chest 2007;132:1920-1926 Correlation Between CECs With sesel And vwf Among Test Subjects Increased cell proliferation activity in the restenotic hemodialysis vascular access after percutaneous transluminal angioplasty Investigated the activity of cellular proliferation of restenotic lesions by means of immunohistochemistry, using antibody to PCNA. Specimens from 10 primary stenotic and 20 restenotic lesions of brescia-cimino fistulae obtained during revision Chang et al Am J Kidney Dis 43 : 74 84, 2004 Boos, C. J. et al. Chest 2007;132:1920-1926 5
Human Intestine Vein at Fistula Placement Proliferation Indices in the Primary Stenotic and Restenotic Groups Primary Stenotic Vein Restenotic Vein after BAM Chang et al Am J Kidney Dis 43 : 74 84, 2004 Chang et al Am J Kidney Dis 43 : 74 84, 2004 Increased cell proliferation activity in the restenotic hemodialysis vascular access after percutaneous transluminal angioplasty Smooth Muscle Cell Proliferation is Proportional to the Degree of Balloon Injury Proliferation index of the restenotic group was significantly greater than that of the primary stenotic group Proliferation indices correlated negatively with the interval from PTA to restenosis and positively with the number of PTAs per lesion. Chang et al Am J Kidney Dis 43 : 74 84, 2004 Indolfi et al. Circulation. 1995;92:1230-35 6
Vascular Lesion Formation After Balloon Overstretch Injury Day 1 Day 3 Adjusted primary patency rates in surgery ( ) and percutaneous transluminal angioplasty (PTA; ) groups Day 7 Day 14 Copyright 1996 American Heart Association Scott, N. A. et al. Circulation 1996;93:2178-2187 Tessitore, N. et al. Clin J Am Soc Nephrol 2006;1:448-454 Copyright 2006 American Society of Nephrology Maintenance and Salvage of Arteriovenous Fistulas Procedures for Non-Maturing Fistulas 63 Fistulas (42%) required 209 procedures to maintain patency 3.3 procedures per fistula (1.75 procedures per access year) 174 venous angioplasty 18 arterial angioplasty 14 thrombectomy 3 ligation of side branches 2 stents Falk A, JVIR 2006 Falk A, JVIR 2006 7
Angioplasty and Venous Stenosis Still room for improvement 36-62% restenosis rate within 6 months in patients who underwent PTA Animal models of angioplasty showed SMC proliferation to be proportional to degree of vascular injury Venous smooth muscle cells (SMC) have been shown to be more sensitive to the effects of antiproliferative agents as compared to arterial SMCs. Poor integrity of internal elastic laminae of the venous wall compared with those of the arterial wall 450 ml/min Elastic Stenosis 2 minutes: 620 ml/min 3 minutes: 570 ml/min 4 minutes: 510 ml/min 5 minutes: 480 ml/min BAM!! Vessel Rupture High-grade stenosis + non-compliant balloon = vessel rupture BAM!! What does Angioplasty do? 1. Makes us feel better? 2. Makes the patient feel better? 3. Provides durable treatment to a diseased vessel? 4. Injures the vein it s trying to help? 5. Helps support our practice and the companies that make balloons? 8
Can Fistula Stenosis Be Treated? Surgical revision with patch-angioplasty or bypass Mechanical dilation of the artery and outflow vein Dilation followed by stent placement No medical (non-mechanical) therapy has been shown to treat fistula stenosis 9