Development and validation of an ex vivo porcine model of functional tricuspid regurgitation

Background and Aim: Ex vivo models of functional tricuspid regurgitation (FTR) are needed for pre-clinical testing of novel surgical and interventional repair strategies, but current options are costly or have not been formally validated. The objective of this research was to create and validate an ex vivo model to test novel repair methods for FTR. Methods: In explanted porcine hearts, the right atrium was excised to visualize the tricuspid valve. The pulmonary artery and aorta were clamped and cannulated, the coronary arteries ligated, and the right and left ventricles statically pressurized with air to 30 mmHg and 120 mmHg, respectively. FTR was induced by increasing right ventricular pressure to 80 mmHg for 3 h, which resulted in progressive tricuspid annular enlargement, right ventricular dilation, papillary muscle displacement, and central tricuspid malcoaptation. A structured light scanner was used to image the 3D topography of the tricuspid valve in both the native and FTR state, and images were exported into scan-to-computer-aided design software, which allowed for high-resolution 3D computational reconstruction. Relevant geometric measurements were sampled including annular circumference and area, major and minor axis diameter, and tenting height, angle, and area. Geometric measurements from the ex vivo model were compared to clinical transthoracic echocardiographic (TTE) measurements using two-sample t-tests. Results: A total of 12 porcine hearts were included in the study. Annular measurements of the native valve were comparable to published TTE data, except for the minor axis diameter, which was shorter in the ex vivo model (2.5 vs. 3.1 cm, P = 0.007). Induction of FTR in the ex vivo model resulted in annular enlargement (FTR vs. native: circumference 13.7 vs.11.8 cm, P = 0.012; area 14 vs. 11 cm2, P = 0.011). Ex vivo leaflet measurements in both the native and FTR model differed from published TTE data, but demonstrated comparable directional changes between the native and regurgitant states, including increased tenting height, area, and volume. Conclusion: The ex vivo pneumatically-pressurized porcine model closely recapitulates the geometry of both the native and regurgitant tricuspid valve complex in humans and holds promise for testing novel FTR repair strategies. Relevance for Patients: Currently available interventions for the tricuspid valve have a risk of permanent conduction abnormalities and are insufficient in addressing tricuspid disease for a subset of patients. This ex vivo model provides a platform for testing of novel interventions that address the deficiencies of current tricuspid therapies.