Targeting a Low INR Level in Patients with Mechanical Heart Valve Prostheses: a Systematic Review of the Literature

Abstract

The past 50 years have witnessed remarkable progress in the development of safe, hemodynamically favorable mechanical heart valves. Much of that progress has come about by simple trial and error and certainly some has resulted from unexpected fortuitous events. It is remarkable that two of the six mechanical heart valves currently available for implantation (the Starr-Edwards ball valve and the St. Jude Medical bileaflet valve) are virtually unchanged from the original models implanted in 1965 and 1977, respectively. Four other mechanical valves approved for implantation(Omniscience, Omnicarbon, Medtronic-Hall, and Carbomedics valves) have been in use for more than 16 years with essentially no mechanical failures. Pyrolytic carbon, a compatible and virtually indestructible biomaterial that has been adapted from the nuclear fuel industry, has enabled much of the progress. Eventually, with the right valve design and the right valve material, it is conceivable that we may someday have a mechanical valve that does not require lifelong anticoagulation therapy. The overall complications associated with prosthetic heart valves can be divided into six main categories: structural valvular deterioration, non-structural dysfunction, valve thrombosis, embolism, bleeding and endocarditis. On the one hand, bioprosthetic heart valves are plagued with leaflet calcification and leaflet tearing. On the other, mechanical heart valves are associated with haemolysis, platelet activation and thromboembolic events arising from clot formation and their subsequent detachment. These complications are believed to be associated with non-physiological blood flow patterns in the vicinity of heart valves. The performance of artificial heart valves is closely governed by the fluid mechanics within these valves, which, in turn, is strongly related to the geometry, material and mechanism of the valve design. The obvious engineering challenge is to design an optimal heart valve. Such a challenge is currently being pursued in three main directions. In the first direction, researchers have taken a step back from the concept of artificial devices and have taken the route of engineering a living tissue valve with as many characteristics of the native heart valve as possible. In the second direction, engineers are developing advanced computational fluid dynamics (CFD) tools to accurately predict the fluid mechanics in the vicinity of heart valves down to the resolution of individual blood cells. Finally, in the third direction, research is being conducted to pinpoint the exact coagulation mechanisms triggered by haemodynamics in heart valves using ex vivo and in vitro experiments, thus opening avenues to improve on existing designs based on direct coagulation measures. The patients with prosthetic heart valves require chronic oral anticoagulation, and so physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. The estimated risk of a thromboembolic event depends on the type of prosthesis and its anatomical position (aortic, mitral, or tricuspid).There are no universal dosage recommendations for VKAs, but rather each patient should have their therapy tailored via serial INR monitoring. The incidence of major bleeding in patients with mechanical valves treated with warfarin, or its derivatives, is approximately 1.4 per 100 patient-years. The incidence of major embolism (defined as causing death, residual neurologic deficit, or peripheral ischemia requiring surgery) in the absence of antithrombotic therapy for patients with mechanical valves has been suggested to be approximately 4 per 100 patient-years. This risk decreases to 2.2 per 100 patient-years with only antiplatelet therapy, and is further reduced to 1 per 100 patient-years with warfarin, including valves in both the mitral and aortic positions.