Flow Forward Medical has announced the completion of a preclinical study and a computational fluid dynamics study supporting continued development of the company’s Arteriovenous Fistula Eligibility (AFE) system. The AFE system is a small external blood pump designed for temporary use to stimulate flow-mediated vein dilation to make more haemodialysis patients eligible for creation of arteriovenous fistula (AVF) and arteriovenous graft (AVG) vascular access sites, and to increase success rates after AVF and AVG surgeries.
In the non-clinical study, which was supported by Small Business Innovation Research (SBIR) Grant awarded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), ovine cephalic veins were treated for six days with the AFE system. Maximum vein diameter increased on average 89% from 5.5mm to 10.4mm with treatment. At the time of AVF creation, outflow cephalic veins were of larger average diameter in AFE system-assisted AVFs than in control AVFs, while inflow brachial arteries had similar diameters. After six weeks, both inflow arteries and outflow veins were larger in AFE system-assisted AVFs than in control AVFs, suggesting improved AVF maturation. An independent analysis of outflow veins of the AVFs created using the pre-treated veins demonstrated an average blood flow rate 398% higher than AVFs created using untreated veins (1712 mL/min versus 344 mL/min) after six weeks of maturation. An independent histology review of these AVFs at six weeks indicated the average cross-sectional area of AVF inflow arteries and outflow veins was 10.6mm2 and 200mm2, respectively, for pre-treated AVFs, and 5.3mm2 and 86mm2, respectively, for control AVFs.
“These data further validate the rapid rate of vein dilation during AFE system treatment. We now believe that 7–14 days of treatment is likely to be enough for most patients,” said president and chief executive officer Nicholas Franano. “This study also suggests that the overall rate and time required for AVF maturation, and the duration of primary and secondary AVF patency are likely to be positively affected by the treatment of veins with the AFE system prior to AVF surgery.”
Flow Forward also announced the completion of a computation fluid dynamics study in partnership with the research group of Yan-Ting Shiu in the Division of Nephrology & Hypertension at the University of Utah, USA. This study used bench flow loops and computation fluid dynamics modelling to compare blood flow, pressure, wall shear stress , wall motion in AVF and AFE system outflow veins, and determined the effect of outflow vein diameter on these important biomechanical factors.
Elevated wall shear stress stimulates AVF outflow vein dilation during AVF maturation, increasing the likelihood of successful AVF use for haemodialysis. However, this elevated stress may demonstrate a “Goldilocks effect”, such that when elevated stress levels are not high enough, vein dilation is inadequate or slow, while when stress levels are too high, vein walls can be damaged. The study carried out by Flow Forward and the University of Utah suggests that peak wall sheer stress levels are very high in AVF outflow vein segments adjacent to the anastomosis, indicating a high likelihood of vein wall damage. This effect was especially pronounced with small veins, which is consistent with the recent finding that 86% of forearm AVFs failed to mature at six weeks without intervention seen in the recent human fistula maturation study funded by the NIH. In the Flow Forward study, wall sheer stress levels were also elevated in AFE system outflow veins, but peak stress levels were much lower than with AVF, indicating a lower risk of vein wall damage.
Cyclic stretching of venous smooth muscle cells has also been implicated in AVF failure. This study suggested that AVF outflow vein segments adjacent to the anastomosis experience cyclic stretching due to the pulsatile nature of the blood flowing from the inflow artery, with the greatest amount of displacement and stretch seen with the smallest AVF outflow veins. Conversely, due to the non-pulsatile nature of the blood flowing from the AFE system, there is no cyclic stretch of the outflow vein wall.
“We believe developing a better understanding of the causes of AVF failure can aid in the development of medical devices and treatment methods to increase AVF maturation success, and primary and secondary AVF patency rates,” said Franano. “It is encouraging to see that the AFE system can consistently deliver optimal doses of wall shear stress to veins using non-pulsatile blood flow, providing an ideal environment for rapid vein maturation.”
Alongside this news, Flow Forward announced the issuance of US patents for the AFE system, protecting methods for using blood pump systems to dilate peripheral veins prior to vascular access site surgery.
Flow Forward also announced the closing of US$1m in additional Series A financing, led by a group of individual investors. This financing will support the further development of the AFE system. The company had previously raised US$6m in Series A funding, bringing the total funding raised to US$7m to date
