A Model of Heterotopic Aortic Valve Replacement for Studying Thromboembolism Prophylaxis in Mechanical Valve Prostheses

Abstract

New anticoagulants, such as direct thrombin inhibitors, have been evaluated in prevention of thromboembolism associated with atrial fibrillation and may also be useful for thromboprophylaxis of mechanical heart valves. Preclinical studies are necessary prior to human trials, but the best animal model is unknown. We, therefore, compared thrombogenicity in two porcine models of mechanical valve replacement, a standard preparation for mitral valve implantation and a simplified heterotopic model of aortic valve replacement. Thirteen swine underwent either mitral valve replacement (n = 6) or heterotopic aortic valve replacement (n = 7) with bileaflet mechanical valve substitutes. The heterotopic aortic valve replacement consisted of an extra-anatomical, modified valved conduit bypassing the ligated native descending thoracic aorta. At 30 d, the animals were sacrificed and the amount of valve thrombus was measured. Infectious vegetations were present on two valve prostheses in animals with orthotopic mitral valves and were excluded. Mean thrombus weight for the remaining valves was 216 +/- 270 mg [95% CI -35, 466] for the animals with heterotopic aortic valve replacement and 74 +/- 67 mg [95% CI -33, 180] for animals with orthotopic mitral valve replacement (P = 0.5). A porcine, heterotopic aortic mechanical valve replacement model appears to incite more thrombus formation than does an orthotopic mitral valve replacement model. This appears to be a more stringent model for initial testing of novel anticoagulation strategies for mechanical heart valve thromboprophylaxis.