Arteriovenous Fistula Creation using the Optiflow Vascular Anastomosis Device: A First in Man Pilot Study Roberto J. Manson,* Adrian Ebner,† Santiago Gallo,† Eric Chemla,‡ Mark Mantell§ David Deaton,– and Prabir Roy-Chaudhury** *Department of Surgery, Duke University Medical Center, Durham, North Carolina, †Department of Surgery, Hospital Privado Frances, Asuncion, Paraguay, ‡Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, §Department of Transplant Surgery, St Georges Health Trust, London, United Kingdom, –Division of Vascular Surgery, Georgetown University Hospital, Washington DC, and **Dialysis Vascular Access Research Group, Division of Nephrology, University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, Ohio ABSTRACT Although arteriovenous fistulae are the preferred form of dialysis vascular access they continue to have significant problems with maturation failure. The Optiflow device is a sutureless anastomotic conduit which could potentially reduce surgical time and also standardize the surgical procedure. We report herein on the ‘‘First in Man’’ experience with the Optiflow device. Arteriovenous Fistula (AVF) nonmaturation is currently a huge clinical problem with a very significant morbidity and economic cost (1–5). The primary patency of AVFs is thought to be around 50% at 1 year and a recent large study demonstrated that up to 60% of AVFs were not suitable for dialysis at between 4 and 5 months postsurgery (6). The most common cause of AV fistula nonmaturation is the early and aggressive occurrence of a peri-anastomotic stenosis (7). At a pathogenetic level, AVF nonmaturation is likely to be due to a combination of small starting vessels, an aggressive neointimal hyperplasia, and an inability to dilate appropriately in response to increases in blood flow (5,8,9). The Optiflow device is a novel anastomotic implant that results in a highly reproducible anastomosis with controlled geometry between the artery and vein. The device also has the potential of shielding the peri-anastomotic region, which is prone to develop stenosis. A chronic pig study in our laboratory (n = 6) demonstrated a significant decrease (Fig. 1; albeit possibly with some component of increased ex-vivo collapse of the vein in the Control group) in the percentage (%) luminal stenosis at the venous portion of the arteriovenous anastomosis (AV-V) in the Optiflow group (5.1±1.5% for Optiflow vs 32.4±7.8% for Control; mean ± SD; p < 0.05, paired t-test). There were no significant device-related adverse events. Thus, initial experimental studies performed in pig models in our laboratory (10) were able to demonstrate both safety and possible efficacy, allowing us to move into the First in Man studies described herein. The objective of this study was to evaluate the technical feasibility, safety, and clinical success of the Optiflow implant (Fig. 2) for creation of an arteriovenous fistula (AVF). Address correspondence to: Prabir Roy-Chaudhury MD, PhD, FASN, Division of Nephrology, University of Cincinnati, MSB 6009, 231, Albert Sabin Way, Cincinnati OH, 452670585, Tel.: (513) 558-4006, Fax: (513) 558-4309, or e-mail: roychap@ucmail.uc.edu. Seminars in Dialysis—2012 DOI: 10.1111/j.1525-139X.2012.01062.x ª 2012 Wiley Periodicals, Inc. Fig. 1. Decrease in venous anastomotic stenosis in a pig model: Note the significant decrease in stenosis within the venous portion of the arteriovenous (AV) anastomosis in animals treated with the Optiflow device as compared with a hand-sewn anastomosis. AV-V, venous portion of the AV anastomosis; AV-A, arterial portion of the AV anastomosis; Vein, proximal venous segment beyond anastomosis. 1 2 Manson et al. Methods End-to-side radial-cephalic, brachial-cephalic, and brachial-basilic fistulas were created using the Optiflow Implant (3 or 4 mm) in 10 patients using a combination of standard and Optiflow specific surgical techniques. In brief, the artery and vein were dissected out following which the vein was transected and the venous conduit placed into the vein and secured with two circular stay sutures. The length of vein with the Optiflow was then sized again to make sure the vein length was appropriate. The artery was then isolated with vessel loops and a punch arteriotomy was made in the artery. The flanges of the device were then inserted into the arteriotomy and pulled back to ensure that the anastomosis was firm. The vessel loops were then released and the anastomosis examined for any bleeding or oozing (Fig. 3). The primary safety endpoint for this study was freedom from severe and unanticipated adverse events at 42 days postsurgery, whereas the primary efficacy Vein Artery Fig. 4. Duplex Doppler of an Optiflow: Color Doppler of an Optiflow device. Note the clearly defined anastomotic angle. Conduit Flange Fig. 2. Optiflow: Note the two flanges, which insert into the arteriotomy as also the venous conduit that goes into the vein. The end result is a sutureless anastomosis albeit with two circular sutures, which keep the vein in place over the venous conduit. Vein Artery Fig. 5. AVFs created with the Optiflow: Note two AVFs created using the Optoflow. The arrows in the left panel point to needlestick holes indicating that this was a functional AVF that was being used for hemodialysis. endpoint was technical success following the procedure. The secondary efficacy endpoint was primary patency at 42 days as confirmed by ultrasound (Fig. 4) and clinical exam (Fig. 5). Results Fig. 3. Optiflow in a subject: Note the final intra-operative picture with no bleeding and a dilated outflow vein with two circular sutures. Six male and four female subjects were enrolled in the study. The mean patient age was 45 years (±12.2 years). The primary efficacy endpoint of technical success following the procedure was achieved for all 10 subjects, as was the primary safety endpoint of freedom from severe or unanticipated adverse events. In addition, nine of the 10 subjects achieved the secondary efficacy endpoint of primary patency at 6 weeks defined 3 OPTIFLOWTM FOR AVF CREATION Fig. 6. Change in venous diameter following Optiflow placement: Note the increase in venous diameter following Optiflow placement. In particular, note that all AVFs created with the Optiflow have achieved the 6-mm diameter suggested by the KDOQI guidelines at 42 days. as the lack of thrombosis or an interventional procedure needed to maintain patency. One patient had a pseudoaneurysm prior to day 21, which was attributed to an accident during cannulation. This patient’s fistula was patent at day 42. Of note, vein diameters at day 42 exceeded the minimum 6 mm diameter specified in the DOQI guidelines in all patients (Fig. 6). Of particular relevance was the fact that early cannulation (prior to day 21) was successfully performed on two patients. Finally, the surgeon of record was asked to provide a subjective surgical assessment at the end of surgery and in general this suggested excellent immediate dilation and reduction of time compared with historical controls. opens the door for larger studies of this device, which are currently in progress. Acknowledgments Dr. Roy-Chaudhury is supported by NIH 5U01-DK82218, NIH 5U01-DK82218S (ARRA), NIH 5R01-EB004527, NIH 1R21-DK089280-01, NIH 1R01DK088777 (MPI), a VA Merit Review, a University of Cincinnati NIH ⁄ NCCR UL1RR026314 CTSA grant, and industry grants from WL Gore, Shire and BioConnect Systems. Disclosures Discussion Although the Fistula First initiative and other measures have resulted in a very significant increase in AVF prevalence from 24% in 2003 to 60% currently, it has also unmasked an epidemic of early fistula failure caused by nonmaturation (an inability to increase diameter and blood flow sufficiently to support dialysis). The exact reasons for this problem are unclear but include: (i) the placement of AVFs in patients with multiple co-morbidities and small calcified vessels, (ii) possible inadequate training of surgeons in the proper placement of AVFs, and (iii) an aggressive peri-anastomotic stenosis as a result of surgical injury and hemodynamic stressors. Of note, the Optiflow device could counter many of these problems by providing a fixed outflow diameter, by shielding the peri-anastomotic region and perhaps also by standardizing surgical technique and thus leveling the playing field in terms of the surgical expertise required in individual cases. It is important to emphasize that the current First in Man study, in essence demonstrates technical feasibility and safety. In particular, there were no problems with malposition, migration, hemorrhage, and infection in these 10 patients. Clearly, as this was a First in Man study, we used subjects with adequate rather than small vessel diameters but additional studies will investigate use of the device in smaller vessels. Although additional investigations are clearly needed to provide solid efficacy data in terms of primary and cumulative patency, we believe that this pilot study Dr. Roy-Chaudhury is a Consultant ⁄ Advisory Board member and research contract recipient with Bioconnect Systems. Drs Manson, Mantell and Deaton are Advisory Board members for Bioconnect Systems. References 1. Roy-Chaudhury P, Kelly BS, Melhem M, Zhang J, Li J, Desai P, Munda R, Heffelfinger SC: Vascular access in hemodialysis: issues, management, and emerging concepts. Cardiol Clin 23:249–273, 2005 2. Roy-Chaudhury P, Kelly BS, Melhem M, Zhang J, Li J, Desai P, Munda R, Heffelfinger SC: Novel therapies for hemodialysis vascular access dysfunction: fact or fiction! Blood Purif 23:29–35, 2005. 3. Roy-Chaudhury P, Kelly BS, Narayana A, Desai P, Melhem M, Munda R, Duncan H, Heffelfinger SC: Hemodialysis vascular access dysfunction from basic biology to clinical intervention. Adv Ren Replace Ther 9:74–84, 2002 4. Roy-Chaudhury P, Kelly BS, Zhang J, Narayana A, Desai P, Melham M, Duncan H, Heffelfinger SC: Hemodialysis vascular access dysfunction: from pathophysiology to novel therapies. Blood Purif 21:99–110, 2003 5. Roy-Chaudhury P, Sukhatme VP, Cheung AK: Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint. J Am Soc Nephrol 17:1112–1127, 2006 6. Dember LM, Beck GJ, Allon M, Delmez JA, Dixon BS, Greenberg A, Himmelfarb J, Vazquez MA, Gassman JJ, Greene T, Radeva MK, Braden GL, Ikizler TA, Rocco MV, Davidson IJ, Kaufman JS, Meyers CM, Kusek JW, Feldman HI: Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 299:2164–2171, 2008 7. Roy-Chaudhury P, Arend L, Zhang J, Krishnamoorthy M, Wang Y, Banerjee R, Samaha A, Munda R: Neointimal hyperplasia in early arteriovenous fistula failure. Am J Kidney Dis 50:782–790, 2007 8. Lee T, Roy-Chaudhury P: Advances and new frontiers in the pathophysiology of venous neointimal hyperplasia and dialysis access stenosis. Adv Chronic Kidney Dis 16:329–338, 2009 9. Roy-Chaudhury P, Spergel LM, Besarab A, Asif A, Ravani P: Biology of arteriovenous fistula failure. J Nephrol 20:150–163, 2007 10. Roy-Chaudhury P, Wang Y, Krishnamoorthy M, Dakin A: Optiflow: a novel anastomotic conduit for reducing av fistula dysfunction. J Am Soc Nephrol 19:253A, 2008