No description available.

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.

Chronic Venous Insufficiency (CVI) is a condition in present in almost 27% of adults in which an insufficient amount of blood is pumped back to the heart due to damaged or poorly apposed one-way valves in the leg veins. During forward flow, vein valves allow blood to return to the heart while posing very little resistance to the flow. During gravity-driven reverse flow, normal valves close and prevent blood from flowing backward through the valve. Incompetent, or damaged, vein valves cannot prevent this reverse flow and lead to a pooling of blood at the feet. CVI is a painful disease presents itself in various ways, including varicose veins, ulcerations of the lower extremities, and severe swelling. Current therapies and treatments include compressive stockings, destruction or removal of affected veins, valve repair, and valve transplants. The implantation of prosthetic vein valves is a future treatment option that does not require an invasive surgery, human donor, or lengthy hospital stay. While no prosthetic vein valves are currently commercially available, this thesis describes the design, verification, and validation of a novel prosthetic vein valve. Verification tests include CFD simulations, functional tests, mechanical tests, and in vitro thromogenicity tests. The validation of the device was done through an animal study in sheep external jugular veins. CFD analysis verified that shear rates within the valve support its lower thrombogenicity as compared to a previous vein valve. Benchtop tests demonstrate superiority in short-term patency over a previous polymer valve. In a sheep study, patency was shown at 6 weeks, surpassing many autograft valves and showing great potential to meet the goal of 3 month patency in sheep.

No description available.

Venous disease will affect 1-3% of the western world at some point in their lives, yet there are few effective treatments for the venous system [1]. One such disease is chronic venous insufficiency (CVI), a painful and debilitating illness that affects the superficial and deep vein valves of the legs. When the valves become incompetent they allow reflux and subsequent pooling of blood. Current clinical therapies are only moderately; and therefore, the need for a better solution remains. Prosthetic venous valves were constructed from a novel hydrogel biomaterial patented by Georgia Tech. The valves had flexible cusps similar to normal, anatomic venous valves. The purpose of this work was to evaluate the thrombotic potential of the GT venous valve in an in vitro study and to design a percutaneous delivery system. In vitro thrombosis model provides an appropriate intermediate step between valve development and in vivo analysis, which is necessary to determine the biocompatibility of the prosthetic device. The flow system was modified from a one-pass, flow-through thrombosis assay using whole blood [2] to mimic pulsatile physiologic conditions. Cessation of flow indicated thrombotic obstruction. Histological analysis was performed using H and E staining and Carstairs stain (specific for platelets). A group of valves were lined with Dacron to confirm the thrombotic potential of the system. All Dacron valves were occluded by thrombus connecting the polymer fibers with adherent platelets. Whole blood perfused through the GT prosthetic valves exhibited no thrombosis or platelet adherence. All GT valves were patent and competent after blood perfusion. H and E staining revealed no thrombus deposition on the GT vein valves. A percutaneous delivery system was designed after evaluating the GT valves for their compressibility and plastic deformation over time. Appropriate stents, catheters and sheaths were selected. As designed, this system will be utilized in an ovine trial of the valve. Due to the low in vitro thrombotic potential and strong history of PVA as a medical implant material, positive trial results are expected. With successful animal and human trials this valve can provide a potential intervention for the 7 million people suffering from CVI.