Development and evaluation of a swine model to assess the preclinical safety of mechanical heart valves

Background ann aim of the study: The current standard of in vitro and in vi vo preclinical heart valve testing has recently been questioned because of its failure to reveal the thrombogenic potential of the Medtronic Parallel( TM) prosthetic valve. The aim of this study was to develop a swine model fo r the in vivo preclinical evaluation of mechanical heart valves, and to ass ess the ability of this model to identify mechanical heart valve design fea tures that result in valve-related thrombosis. Methods: Twenty-two swine underwent mitral valve replacement (MVR) using th ree different bileaflet mechanical valve designs (St Jude Medical, CarboMed ics, Medtronic Parallel). Each animal was placed in an anticoagulation prot ocol (group I, INR 3.0-3.5; group II, INR 2.0-2.5; group III, no anticoagul ation) and followed for up to 20 weeks. Terminal studies were performed on all animals surviving for more than 30 days. Results: Twenty-one animals survived the immediate postoperative period. Fo ur of six group I animals died from hemorrhagic (large wound hematoma; hemo pericardium) complications early in the study. In the two long-term (61 and 89 days) survivors, INRs of 3.0 to 3.5 were never achieved (61-day survivo r, mean INR 2.0 +/- 1.03; ranger 0.8-5.4; 89-day survivor, mean INR 1.92 +/ - 1.34; range: 1.0-7.9). Pathological analysis of explants from group I sur vivors revealed minimally obstructive fibrous sheathing on the inflow orifi ce without restriction of bileaflet motion (61 and 89 days), and two large perivalvular defects (61 days). Six of seven group II animals died from ear ly hemorrhagic complications (hemopericardium) (mean INR 2.32 +/- 1.84; ran ge: 0.8-8.2). Vegetations resulting in obstruction of both sides of the val ve orifice and restriction of bileaflet motion were observed in a group II survivor (mean INR 2.33 +/- 1.58; range: 0.9-7.0). Group III animals (n = 8 ) survived for a mean of 106 +/- 60 days (range: 1-177 days). In group III, fibrous sheathing was present on all explanted valves and organized thromb i in six valves; orifice obstruction (seven valves) and restriction of bile aflet motion (three valves) were also observed. Conclusion: The use of MVR in swine as a preclinical model to evaluate the safety and performance of mechanical heart valves is limited by: (i) diffic ulty in maintaining safe levels of anticoagulation with warfarin, resulting in a high incidence of hemorrhagic complications; (ii) marked fibrous shea th formation and associated thrombosis; and (iii) an increased incidence of perivalvular defects, believed to result from normal somatic growth occurr ing in young swine.