Department of Vascular Surgery, Maastricht University, Maastricht - The Netherlands 2

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Magdalen Carter
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1 The Journal of Vascular Access 2007; 8: ORIGINAL ARTICLE Accessory veins and radial-cephalic arteriovenous fistula non-maturation: a prospective analysis using contrast-enhanced magnetic resonance angiography R.N. PLANKEN 1,2,5, L.E. DUIJM 6, A.G. KESSELS 4, T. LEINER 2,5, J.P. KOOMAN 3,5, F.M. VAN DER SANDE 3,5, J.H.M. TORDOIR 1,5 1 Department of Vascular Surgery, Maastricht University, Maastricht - The Netherlands 2 Department of Radiology, Maastricht University, Maastricht - The Netherlands 3 Department of Nephrology, Maastricht University, Maastricht - The Netherlands 4 Clinical Epidemiology and Medical Technology Assessment, Maastricht University, Maastricht - The Netherlands 5 Cardiovascular Research Institute Maastricht (CARIM) - The Netherlands 6 Department of Radiology, Catharina Hospital, Eindhoven - The Netherlands Abstract: Purpose: To determine if large caliber accessory veins are associated with radial-cephalic arteriovenous fistula (RC-AVF) non-maturation. Methods: RC-AVFs were created in 15 consecutive patients (radial artery and cephalic vein diameter >2 mm, in the absence of arterial inflow or venous outflow stenoses or occlusions). Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed preoperatively for the determination of vessel diameters, stenoses and occlusions. The location and caliber of accessory veins was determined. Vascular access (VA) function was monitored and all interventions required to obtain a functioning VA were recorded. Non-maturation was defined as a nonfunctional VA at 2 months after creation. The predictive value of accessory vein caliber for prediction of RC-AVF non-maturation was evaluated using receiver operating characteristic (ROC) analysis. Results: Non-maturation occurred in 10 (67%) out of 15 RC-AVFs. Large caliber accessory veins (n=4), venous stenosis (n=3) or both (n=2) were associated with RC-AVF non-maturation. The presence of large caliber accessory veins was the only significant predictor for RC-AVF non-maturation (p=0.01). Preoperatively detected accessory veins with a diameter >70% of the cephalic vein diameter, had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 80, 100, 100 and 91% for prediction of RC-AVF non-maturation on patient level. Accessory vein ligation and dilatation of venous stenosis resulted in an overall salvage success rate of 89% (8/9). Conclusion: Large caliber accessory veins are associated with RC-AVF non-maturation. Ligation of large caliber accessory veins is a successful salvage procedure in a substantial group of patients. Furthermore, ligation of these accessory veins during initial RC-AVF creation can potentially reduce non-maturation rates; and therefore, preoperative assessment of accessory veins is recommended. (J Vasc Access 2007; 8: 281-6) Key words: Arteriovenous (AV) fistulae, Hemodialysis access, Ligation of accessory veins INTRODUCTION Autogenous arteriovenous fistulas and the radial-cephalic arteriovenous fistula (RC-AVF) in particular are considered the first choice vascular access (VA) for long-term hemodialysis (HD) treatment because of fewer complications when compared to AVGs or central venous catheters (CVCs) (1, 2). A major drawback of AVFs is the high incidence of shortterm complications such as access thrombosis ( early failure ) or failure to mature to the point where a reasonably experienced dialysis access technician could place two needles in the VA for HD purposes ( non-maturation ). Wichtig Editore, /281-06$15.00/0

2 Accessory veins are associated with RC-AVF non-maturation Clinical utilization of preoperative assessment is recommended by the European and K-DOQI guidelines on vascular access to improve vascular access outcomes. However, despite the use of preoperative vessel assessment up to 50% of all newly created RC- AVFs fail to mature (3, 4). Early failure and non-maturation are serious complications because they necessitate additional intervention and the use of CVCs, which themselves are associated with a risk of future VA failure (5). In the event of non-maturation, salvage can be achieved in up to 92% of cases by the ligation of accessory veins and the dilatation of stenoses (6). However, the exact significance of accessory veins remains a matter of discussion (6-10). After the creation of the arteriovenous anastomosis, both diameter and volume-flow of the main draining vein (the vessel segment to be punctured) increase. This allows recurrent cannulation and efficient HD. If the diameter of the venous segment to be punctured fails to increase >5 mm or if the volume-flow fails to increase >500 ml/min at 2-4 months after creation, the risk of VA non-maturation increases significantly (10). A parameter analysis using a lumped parameter model showed that accessory veins located at preferred puncture sites (ie the forearm), reduces the volume-flow through the vessel segment at the preferred puncture site (11). In the light of these findings, large caliber accessory veins at a preferred puncture site may contribute to RC-AVF non-maturation by reducing the volume-flow in the venous segment to be punctured. The purpose of this study was to prospectively determine if large caliber accessory veins are associated with RC-AVF non-maturation. MATERIALS AND METHODS Our institutional policy is to create RC-AVFs for HD if patients have an arterial inflow and venous outflow free of stenoses or occlusions and a vessel diameter >2 mm of the radial artery and cephalic vein (2). All patients who were candidates for RC-AVF creation were considered eligible for inclusion. The medical ethics committee of the institution approved the study and all patients signed informed consent prior to inclusion. Contrast-enhanced magnetic resonance angiography All patients underwent contrast-enhanced magnetic resonance angiography (CE-MRA) prior to RC-AVF creation. CE-MR images were acquired using a commercially available 1.5-T MR scanner (Intera R9.1, Philips Medical Systems, Best, The Netherlands). For each patient a maximum dose of 45 ml of gadopentate dimeglumine (Gadolinium DTPA, Magnevist, Schering, Berlin, Germany) was used and special care was taken not to exceed 0.3 mmol/kg. The entire upper extremity vasculature was scanned in two separate stations, the thoracic/proximal station and the forearm station, respectively, according to the scan protocol by Planken et al (12). Scans of the forearm superficial veins were acquired after the application of a tourniquet around the upper arm at 60 mmhg. One observer analyzed the CE-MRA images using the dynamic 3D CE-MRA scan, which exhibited the best selective arterial and venous enhancement. The reviewer used maximum intensity projections (MIPs) and multi-planar reformations (MPRs) and had the availability over all source images. Analysis included the assessment of the complete arterial inflow and venous outflow. The diameter of the radial artery and cephalic vein were measured at 5 cm proximal to the distal radial head. The presence of inflow or outflow stenoses and occlusions was recorded. A stenosis with >50% luminal diameter reduction was considered clinically significant. Furthermore, the location and caliber of the cephalic vein side-branches (accessory veins) were assessed. For all accessory veins at the preferred puncture sites (ie cephalic vein sidebranches in the forearm), the caliber in relation to cephalic vein caliber was calculated (accessory vein diameter/cephalic vein diameter * 100%). Surgery All RC-AVF operations were performed under local anesthesia by a vascular surgeon with extensive experience in VA surgery. An incision of 3 cm in length was made approximately 5 cm proximal to the distal radial head. Both the radial artery and the cephalic vein were exposed. The cephalic vein was mobilized to approximate the radial artery after distal cephalic vein ligation. An anastomosis of 10 mm in length was created in a side-to-end fashion (radial artery to cephalic vein). Intra-operative assessment of cephalic vein thrill and flow-velocities by palpation and Doppler analysis were used to determine the RC-AVF function directly after creation. Post-operative assessment of radial-cephalic arteriovenous fistula function Clinical RC-AVF function was assessed at the HD department. Maturation was defined as the ability to use the RC-AVF for two-needle HD as judged in consensus by a nephrologist, vascular surgeon and a dialysis access nurse. Non-maturation was defined as 282

3 Planken et al insufficient access flow and caliber increase within 2 months after RC-AVF creation, making the VA unsuitable for HD access use due to inefficient dialysis or puncture difficulties, respectively. In case of VA early failure or non-maturation salvage procedures were performed (ie percutaneous transluminal angioplasty (PTA), surgical creation of a more proximal anastomosis or ligation of accessory veins). All procedures preformed and their outcomes were recorded. Statistical analysis All statistical analyses were performed using SPSS (SPSS Inc, Chicago, IL) for Windows (Microsoft, Redmond, WA). A stepwise forward logistic regression analysis was used to determine the statistical significance of preoperative parameters (age, gender, co-morbidities, radial artery diameter, cephalic vein diameter, number of accessory veins and accessory vein caliber as percentage of cephalic vein caliber) to predict RC-AVF non-maturation. Values p<0.05 were considered statistically significant. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of preoperatively detected accessory veins for prediction of RC-AVF nonmaturation were calculated using the clinical outcome 2 months post-operative as a standard of reference. The predictive value of accessory veins for prediction of RC-AVF non-maturation was evaluated using receiver operating characteristic (ROC) analysis, in which the sensitivity was plotted against the complement of specificity. For determination of the overall accuracy for prediction of RC-AVF non-maturation by preoperative assessment of accessory vein caliber the area under the ROC curve was calculated (13). RESULTS Fifteen patients had a preoperative radial artery and cephalic vein diameter >2 mm in the absence of inflow or outflow stenoses or occlusions. RC-AVFs were created in all 15 patients. Assessment of RC-AVF function 2 months post-operative revealed only five cases of successful maturation (group A) and 10 cases (group B) of unsuccessful access creation due to access thrombosis (early failure) in one case and nonmaturation in nine cases. Table I summarizes patient characteristics and they were comparable for patients in both groups. Preoperative diameter measurement results were also comparable between both groups (Tab. II). Accessory veins were present in all cases and the number of accessory veins did not differ between group A and group B. Accessory vein caliber (as percentage of cephalic vein diameter) was the only parameter with significant predictive value TABLE I - PATIENT CHARACTERISTICS Group A Group B P-value Age 66 ± ± 15.4 >0.05 Males 60% (3/5) 90% (9/10) >0.05 BMI 27.5 ± ± 3.7 >0.05 PAOD 80% (4/5) 40% (4/10) >0.05 Diabetes 0% (0/5) 20% (2/10) >0.05 Hypertension 60% (3/5) 80% (8/10) >0.05 Values represent ± means standard deviations, BMI = body mass index: kg/m2, PAOD = peripheral arterial occlusive disease TABLE II - PREOPERATIVE CE-MRA MEASUREMENTS Preoperative Group A Group B P-value Radial artery diameter (mm) 2.8 ± ± 0.5 >0.05 Cephalic vein diameter (mm) 2.6 ± ± 0.7 >0.05 Number of accessory veins (n) 2.0 ± ± 1.5 >0.05 Accessory vein caliber* 66.6 ± 10.5% 88.9 ± 8.9% 0.01 Preoperative CE-MRA results for group A patients (successful maturation, n=5) and group B patients (non-maturation, n=10). Values represent means ± standard deviations, * = % of cephalic vein diameter 283

$(* and ** are sensitivity and 1-specificity for cut-off values of 70 and 75% respectively, TPF = true positive fraction, FPF = false positive fraction) for RC-AVF non-maturation as determined by the$

4 Accessory veins are associated with RC-AVF non-maturation Fig. 1 - ROC curve: clinical value of preoperative accessory vein diameter (% of cephalic vein diameter) for prediction of RC-AVF non-maturation. (* and ** are sensitivity and 1-specificity for cut-off values of 70 and 75% respectively, TPF = true positive fraction, FPF = false positive fraction) for RC-AVF non-maturation as determined by the stepwise forward logistic regression analysis (p=0.01). The caliber of accessory veins in group A was smaller compared to group B. ROC analysis revealed an area under the curve of 0.99 for prediction of RC- AVF non-maturation by preoperative assessment of accessory vein caliber (Fig. 1). The presence of accessory veins with a diameter >70% of the cephalic vein diameter predicted RC-AVF non-maturation with sensitivity, specificity, PPV and NPV of 80, 100, 100 and 91% on a patient level, respectively. Figure 2 shows preoperative CE-MRA images of two patients with a failed RC-AVF due to large caliber accessory veins. In one patient, the RC-AVF matured successfully despite the presence of a large caliber accessory vein (79% of the cephalic vein diameter) (Fig. 3). Salvage procedures were performed in 9/10 cases in group B patients with an overall success rate of 89% (8/9). One patient received a renal transplant before a salvage attempt was initiated. In four patients, accessory vein ligation alone was a successful salvage procedure. Dilatation of cephalic vein stenoses was successful in two patients. In another two patients, dilatation of cephalic vein stenoses alone was unsuccessful and accessory vein ligation turned out to be a successful additional salvage procedure. In one Fig. 2 - Preoperative CE-MRA of forearm veins in two patients with RC-AVF non-maturation. Non-maturation was due to cannulation difficulties for venous return. The arrowheads point at accessory veins. Surgical ligation of the accessory veins, indicated by an arrowhead with a star, resulted in successful salvage of the RC- AVFs. The arrow points at the intravenous cannula (can) that resulted in local MR-signal extinction. Fig. 3 - Preoperative CE- MRA of forearm veins in a patient in whom the RC-AVF matured successfully despite the presence and without ligation of a large accessory vein (79% of the cephalic vein diameter). Arrowheads point at accessory veins. An RC-AVF was created successfully in this patient without ligation of accessory veins. The arrow points at the intravenous cannula (can) that resulted in MR-signal extinction. 284

5 Planken et al patient in whom the RC-AVF thrombosed within 2 weeks, dilatation of multiple cephalic vein stenosis and ligation of accessory veins did not result in successful salvage and a new VA was created. Thirteen out of 15 (87%) RC-AVFs were functional after salvage procedures. DISCUSSION The purpose of this study was to prospectively determine the preoperative predictive value of accessory vein caliber for the prediction of RC-AVF nonmaturation, using CE-MRA. In this study population, the presence of large accessory veins at preferred puncture sites prior to VA creation was associated with RC-AVF non-maturation. RC-AVFs failed to mature in 10/15 patients. Although AVFs created at the wrist level are known for higher non-maturation rates compared to AVFs created at the elbow, a non-maturation rate of 67%, observed in this study, is unacceptably high. Both diameter (<5 mm) and volume-flow (<500 ml/min), of the venous vessel segment to be punctured, are associated with RC-AVF non-maturation (10). Although preoperative arterial and venous diameters have been reported to be valuable parameters for prediction of VA maturation, preoperative diameter measurements alone are not enough to overcome non-maturation (3). Other vessel parameters in addition to diameter might also be important to predict VA outcome. We suggested that large caliber accessory veins are disadvantageous for RC-AVF maturation because they can lead to a reduction in both diameter and volume-flow of the venous vessel segment to be punctured. A large caliber accessory vein has a low inflow resistance leading to a diversion of blood flow and a reduction in volume-flow of the vessel segment to be punctured (11). Furthermore, due to the decrease in outflow resistance the intravascular pressure decreases, which also causes a reduction in the diameter of the vessel to be punctured (11, 14). As evidenced by several preceding reports, ligation of accessory veins can be a successful salvage procedure in a substantial number of patients of patients in whom an AVF failed to mature (6). To our knowledge, this is the first report specifically aimed at addressing the clinical significance of assessing accessory veins prior to VA creation to predict RC-AVF non-maturation. Preoperative identification of accessory veins is important because it allows ligation of large caliber accessory veins during initial RC- AVF creation, which can potentially prevent RC-AVF non-maturation. However, in this study, accessory veins were not the only cause of RC-AVF non-maturation. Venous outflow stenoses, not detected by CE- MRA preoperatively, were the cause of non-maturation in a substantial number of patients. As these stenoses were not detected preoperatively, these venous stenoses might have developed after RC-AVF creation. Non-maturation due to de-novo venous stenoses can therefore not be anticipated. This study has limitations; one of them is the limited sample size. Furthermore, CE-MRA was the modality used for this study in patients requiring a HD VA. CE- MRA with the use of gadolinium-containing contrast media in patients with end-stage renal disease (ESRD) is currently discouraged. Recent reports suggest that the use of gadolinium-containing contrast media in ESRD patients may lead to nephrogenic systemic fibrosis (NSF) (15, 16). However, this study was approved by the ethics committee and all data were acquired prior to the FDA safety alert. For clinical purposes, other non contrast-enhanced MRscan protocols or other imaging modalities such as duplex ultrasound might be used for preoperative assessment of accessory veins. CONCLUSION Accessory veins >70% of the venous vessel segment to be punctured are associated with RC-AVF non-maturation. Ligation of these accessory veins is a successful salvage procedure in a substantial number of patients. Furthermore, their ligation during initial RC-AVF creation can potentially reduce non-maturation rates; and therefore, preoperative assessment of accessory veins is recommended. Conflict of interest statement: none declared. Address for correspondence: R. Nils Planken, MD Department of Vascular Surgery, Maastricht University Hospital P. Debyelaan 25 NL-6202 AA Maastricht The Netherlands nilsplanken@gmail.com 285

6 Accessory veins are associated with RC-AVF non-maturation REFERENCES 1. Clinical practice guidelines for vascular access. Am J Kidney Dis 2006; 48 (suppl 1): S Tordoir JH, Mickley V. European guidelines for vascular access: clinical algorithms on vascular access for haemodialysis. EDTNA ERCA J 2003; 29: Allon M, Lockhart ME, Lilly RZ, et al. Effect of preoperative sonographic mapping on vascular access outcomes in hemodialysis patients. Kidney Int 2001; 60: Miller PE, Tolwani A, Luscy CP, et al. Predictors of adequacy of arteriovenous fistulas in hemodialysis patients. Kidney Int 1999; 56: Rayner HC, Pisoni RL, Bommer J, et al. Mortality and hospitalization in haemodialysis patients in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19: Beathard GA, Arnold P, Jackson J, Litchfield T. Aggressive treatment of early fistula failure. Kidney Int 2003; 64: Beathard GA, Settle SM, Shields MW. Salvage of the nonfunctioning arteriovenous fistula. Am J Kidney Dis 1999; 33: Wong V, Ward R, Taylor J, Selvakumar S, How TV, Bakran A. Factors associated with early failure of arteriovenous fistulae for haemodialysis access. Eur J Vasc Endovasc Surg 1996; 12: Turmel-Rodrigues L, Mouton A, Birmele B, et al. Salvage of immature forearm fistulas for haemodialysis by interventional radiology. Nephrol Dial Transplant 2001; 16: Robbin ML, Chamberlain NE, Lockhart ME, et al. Hemodialysis arteriovenous fistula maturity: US evaluation. Radiology 2002; 225: Planken RN, Huberts W, Bosboom EMH, Vosse van der FN, Leiner T, Tordoir JHM. The impact of accessory veins on arteriovenous fistula flow distribution as determined by mathematical flow modeling. In: Henry MH, ed. Vascular Access for Hemodialysis - X. Chicago, IL: Gore, Planken NR, Tordoir JH, Duijm LE, et al. Magnetic resonance angiographic assessment of upper extremity vessels prior to vascular access surgery: feasibility and accuracy. Eur Radiol 2007 Jul 24; (Epub ahead of print). 13. van Erkel AR, Pattynama PM. Receiver operating characteristic (ROC) analysis: basic principles and applications in radiology. Eur J Radiol 1998; 27: Planken RN, Keuter XH, Kessels AG, Hoeks AP, Leiner T, Tordoir JH. Forearm cephalic vein crosssectional area changes at incremental congestion pressures: towards a standardized and reproducible vein mapping protocol. J Vasc Surg 2006; 44: Planken RN, Tordoir JH, Duijm LE, de Haan MW, Leiner T. Current techniques for assessment of upper extremity vasculature prior to hemodialysis vascular access creation. Eur Radiol 2007; 17: Thomsen HS. Nephrogenic systemic fibrosis: A serious late adverse reaction to gadodiamide. Eur Radiol 2006; 16:

NON-MATURED ARTERIOVENOUS FISTULAE FOR HAEMODIALYSIS: DIAGNOSIS, ENDOVASCULAR AND SURGICAL TREATMENT

& NON-MATURED ARTERIOVENOUS FISTULAE FOR HAEMODIALYSIS: DIAGNOSIS, ENDOVASCULAR AND SURGICAL TREATMENT Marko Malovrh* Department of Nephrology, University Medical Centre Ljubljana, Zaloška 7, 1525 Ljubljana,