Large Animal Models of Tricuspid Regurgitation: Relevance, Limitations, and Future Directions.

Despite growing interest in tricuspid regurgitation (TR), evidence remains insufficient to define the optimal timing of intervention and therapeutic strategies, highlighting the need for robust experimental models. Existing large animal models of TR use diverse approaches and can be grouped into two categories: direct valvular interventions targeting the tricuspid leaflets, annulus, or chordae, and indirect induction through mechanisms such as increased right ventricular loading, pulmonary hypertension, or pacing-induced tachycardia. Although direct valvular interventions can reproducibly induce TR and are well suited for modeling primary TR, clinically prevalent secondary TR is driven by annular dilation, leaflet tethering, and right-sided chamber remodeling rather than intrinsic valvular injury. This gap represents a major limitation in the field. In this review, we compare large animal models of TR and outline key considerations to guide model selection, with a focus on approaches that more faithfully reproduce the pathophysiology of TR for mechanistic and translational research.