A variety of valves are positioned within body vessels in animals to permit substantially unidirectional fluid flow through the body vessel from one body location to another. For example, native valves within the heart and veins function to regulate the direction of blood flow within the blood vessels of the body. Heart valves positioned within the heart direct the flow of blood to and from other organs and pump oxygenated blood to the rest of the body. Venous valves are typically bicuspid valves positioned at varying intervals within veins to permit substantially unidirectional blood to flow toward the heart. Body vessels such as veins transport blood to the heart and arteries carry blood away from the heart.
Defects or injury to valves within a body vessel can compromise valve function, thereby disrupting the normal flow of fluid within the body vessel. For example, compromised valve function within a blood vessel may result in an undesirable amount of retrograde fluid flow within the blood vessel across a valve therein, and compromise the unidirectional flow of fluid across the valve. Retrograde fluid flow refers to fluid flow opposite the primary direction of fluid across the valve. For example, for a venous valve, retrograde fluid flow is blood flow away from the heart. Methods of treatment and medical devices suitable for implantation within a body vessel are provided herein.
In the condition of venous valve insufficiency, the venous valve leaflets do not function properly for a variety of reasons. For instance, the vein may become too large in relation to the leaflets so that the leaflets cannot come into adequate contact to prevent backflow (primary venous valve insufficiency), or clotting within the vein may thicken the valve leaflets (secondary venous valve insufficiency). Incompetent venous valves can result in symptoms such as swelling and varicose veins, causing great discomfort and pain to the patient. If left untreated, venous valve insufficiency can result in excessive retrograde venous blood flow through incompetent venous valves, which can cause venous stasis ulcers of the skin and subcutaneous tissue. Venous valve insufficiency can occur, for example, in the superficial venous system, such as the saphenous veins in the leg, or in the deep venous system, such as the femoral and popliteal veins extending along the back of the knee to the groin.
Various implantable medical devices are advantageously inserted within various portions of the body to treat conditions related to compromised valve function within a body vessel. Minimally invasive techniques and instruments for placement of intraluminal medical devices have been developed to treat and repair undesirable conditions within body vessels, including treatment of conditions that affect blood flow such as venous valve insufficiency. Various percutaneous methods of implanting medical devices within the body using intraluminal transcatheter delivery systems can be used to treat a variety of conditions. One or more intraluminal medical devices can be introduced to a point of treatment within a body vessel using a delivery catheter device passed through the vasculature communicating between a remote introductory location and the implantation site, and released from the delivery catheter device at the point of treatment within the body vessel. Intraluminal medical devices can be deployed in a body vessel at a point of treatment and the delivery device subsequently withdrawn from the vessel, while the medical device retained within the vessel to provide sustained improvement in valve function or to increase vessel patency. For example, published U.S. Patent Application US2004/0225352, filed Mar. 10, 2004 by Osborne et al. and incorporated herein by reference in its entirety, describes implantable medical devices comprising a valve for regulating fluid flow through a body vessel. The medical devices may include a valve leaflet attached to a radially-expandable support frame, and configured to permit both fluid flow in a first direction and a controlled amount of fluid flow in a second direction.
One challenge for development of an implantable prosthetic valve with the venous system is mitigating thrombus formation that can occlude the vessel and/or lead to loss of functionality of the valve structures that regulate blood flow. In contrast to the arterial system, the lower flow rates in the deep veins of the legs and feet can lead to stagnation of blood in the pockets about the bases of the leaflets or valve structure due to the inability of the blood to be flushed and refreshed thereabout. The pockets can fill with thrombus that compromises the ability the leaflets or valve structure to open and close in response to antegrade and retrograde flow (i.e., pressure differentials across the valve). For example, fibrinogen absorbed on to the surface of an implanted prosthetic valve can form a layer that triggers the biochemical pathway leading fibrin deposition, platelet aggregation, and thrombus formation.
Remodelable materials, such as extracellular matrix (ECM) materials, can be used to provide a non-thrombogenic surface in an implantable prosthetic valve. Prosthetic valves desirably include valve leaflets formed from a remodelable material such that, upon implantation, the remodelable material can become vascularized to form a permanently non-thrombogenic leaflet surface. Small intestinal submucosa (SIS) is a commercially available ECM material (Cook Biotech Inc., West Lafayette, Ind.) derived from a porcine source and processed to retain remodelability. While the ability of valve leaflets made of ECM materials to remodel has been demonstrated clinically, the surface of the newly-implanted SIS can be vulnerable to thrombus formation, particularly in the pocket regions. Because remodeling is a process that can take 30 days or longer, depending on the environment, thrombogenicity has remained a clinical issue to be addressed when using remodelable biomaterials. Higher levels of both antegrade and retrograde fluid flow across the ECM material may enhance the remodeling process, for example by preventing or reducing stagnation of fluid in contact with the ECM material that may lead to thrombus formation. However, high levels of retrograde fluid flow that promote remodeling of the ECM material may reduce the clinical effectiveness of the valve design.
What is needed are methods and devices for reducing undesirable levels of retrograde fluid flow across a valve within a body cavity while permitting desirably high levels of remodeling of an ECM material within the valve. Methods for providing a flow regulating medical device comprising an ECM material within a body vessel that permit both remodeling of the ECM material and a therapeutically effective level of retrograde fluid flow across the medical device are particularly desirable.