Heart Valve Disease & Therapy – The Value of Translational Animal Models

Abstract

Valvular disease and successful therapy is dependent on a complex interplay of metabolic, hemodynamic / fluid dynamic, neuro‐hormonal and immunologic processes. In order to grasp the mechanism of a disease or evaluate novel therapies, biological systems are needed that are capable of mimicking this fascinating complexity. Due to the closely resembling anatomical landmarks of the valvular apparatus and ventricular cavities as well as intra‐ventricular and intra‐aortic fluid dynamic behavior of blood flow, farm pigs should be considered when there is a need for translational large animal model in the field of heart valve research. The use of 90‐100 kg pigs enables deployment of human grade devices as cardiac dimensions in this weight‐class of animals closely resembles one of adult patients. Further, clinical‐grade echocardiography imaging equipment with minimal adaptations of the application technique can be routinely used for TEE guidance of valvular procedures in experimental projects using this animal species. For navigationally challenging procedures, such as transseptal interventions on the mitral valve, porcine animal model could be humanized by relatively simple surgical intervention. Besides proving researchers with robust, human‐like platform for valvular implant testing and development, porcine models provide exceptional value in investigations of diseases where clinical studies are either impractical, time consuming or unethical. Such being studies of cardiac injury in poly‐trauma or precise hemodynamic effects of valvular regurgitation. In such studies, clinical grade medical equipment (such as standard CT and MRI machines and anesthesia equipment) can routinely be used and novel protocols developed and tested, which can then rapidly be adapted for human use, further closing the translation gap. Finally, experience gathered during preclinical testing and learning curve achieved with translational animal models could and should be used to provide practitioners with a solid starting point when novel valve therapies finally find their way to clinical use. Yet, a certain translational gap still remains.