Chronic Venous Insufficiency (CVI) is characterized by chronic venous hypertension from blood pooling in the lower limbs. The resulting symptoms include leg pain, varicose veins, fatigue, venous edema, skin pigmentation, inflammation, induration, and ulceration. Reflux from incompetent venous valves is a factor in up to 94% of individuals with CVI. Current treatments of CVI include compression stockings, drug therapy, vein disabling, venous stenting, and surgical correction with varying rates of success. However, a minimally invasive correction of deep venous reflux does not currently exist. A transcatheter prosthetic venous valve has the potential to be an effective, minimally invasive treatment for deep venous reflux which could treat up to 1.4 million individuals in the United States suffering from venous ulceration and make more than 1.7 billion dollars each year. Previously developed prosthetic venous valves have had problems with competency, patency, thrombogenicity, biocompatibility, and incorrect sizing. To meet the clinical need a prosthetic valve needs to be developed which succeeds where previous valves have failed. This thesis describes the design, analysis, pre-clinical testing, and evaluation of a novel prosthetic venous valve. Design specifications for an effective prosthetic venous valve were created. Verification tests were developed and performed which demonstrated that the valve met every design specification. Finite element and computational fluid dynamics simulations were performed to analyze the valve and calculated a maximum shear rate of 2300 s-1 in the valve during the high forward flow after a Valsalva maneuver. The valve is made of a biocompatible material that has low thrombogenicity, Poly(vinyl-alcohol) cryogel. On the average, the valve allows less than 0.5 mL/min of reflux at low and high retrograde pressures even after 500,000 cycles, indicating that it will reduce the reflux of individuals with venous reflux by more than 99.4%. The valve closes in less than 0.07 seconds and allows the distal pressure to rise to an average of 7% of the equilibrium pressure 30 seconds after a simulated ankle flexion. The valve increases the outflow resistance an average of 2.3 mmHg*min/L which is much less than obstruction levels,≥ 5 mmHg*min/L. The valve can fit in a 16 French catheter and is capable of percutaneous delivery. The base of the valve is 1.5 times the diameter of the vein in which it is to be implanted to help correct orientation upon deployment. Fluid behind the valve’s leaflets is ejected with a forward flow rate of 400 mL/min, suggesting that thrombus formation will not occur at this location. A stented valve remained patent in a porcine blood flow loop for 3 hours. The valve remains competent without buckling in a constricted vein at rest. The valve can expand to fit a vein with a maximum diameter 1.4 times the valve's initial diameter with low risk of tearing or leaflet prolapse. An IACUC protocol for a 12 week study to test the valve in sheep was prepared and approved. A study to evaluate the valve in humans is proposed with endpoints that can be tested for statistical significance and compared with other treatments for CVI. A set of valves which will correct reflux in the majority of common femoral, femoral, and popliteal deep veins is proposed and a sizing guide for surgeons is provided. The minimum distance between prosthetic valves placed in the same vein segment is 13 cm. A comparison of this valve with previously developed prosthetic venous valves and recommendations for work to be performed in the future are given. The valve proposed in this work is the only valve to meet all design specification for an effective prosthetic venous valve, and therefore shows great potential to be a minimally invasive treatment for deep venous reflux.

Over seven million Americans suffer from Chronic Venous Insufficiency (CVI), a painful and debilitating disease that affects the superficial and deep veins of the legs. Problems associated with CVI include varicose veins, bleeding, ulcerations, severe swelling, deep vein thrombosis, and pulmonary embolism, which may lead to death. The presence of CVI results from damaged (incompetent) one-way vein valves in leg veins. These valves normally allow forward flow of blood to the heart, and prevent blood from pooling at the feet. However, incompetent valves allow reflux of blood, causing clinical problems. There are few effective clinical therapies for treating CVI. Vein valve transplantation is a surgical option for treatment. However, it is often difficult to find suitable donor valves. Very few prosthetic valves developed in the past have demonstrated sufficient clinical or mechanical functionality. Persistent problems include thrombus formation, leaking valves, and valves that do not open at physiologic pressure gradient. The primary objective of this research was to develop a clinically relevant functional prosthetic vein valve. The novel prosthetic valve is flexible, biocompatible, has low thrombogenecity, and is easy to manufacture. It was designed to address well-defined consumer needs and functional design requirements. The valve was required to 1) withstand 300 mmHg of backpressure with leakage less than 1.0 mL/min, 2) open with a pressure gradient less than 5 mmHg, and 3) meet criteria 1 and 2 after 500,000 cycles of operation. The valve met these design requirements in bench testing. The valve can open with a pressure gradient of 2.6 0.7 mmHg, and can withstand 300 mmHg with leakage less than 0.5 mL/min. The valve remained functional after opening and closing over 500,000 times. The valve presented in this research is operationally functional, and is a potential solution for treating venous incompetence in CVI patients.