Current landscape for connective tissue disease associated-pulmonary arterial hypertension: a focus on right ventricular adaptation and failure.

Abstract

Right ventricular (RV) function is the primary determinant of survival in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). A "double hit" hypothesis suggests that RV suffers not only from pressure overload common to all PAH but also from direct insults related to the underlying systemic autoimmunity and inflammation. This likely drives distinct maladaptive remodeling (fibrosis, inflammation) and contributes to the poorer prognosis observed in CTD-PAH compared to idiopathic PAH (IPAH).Comprehensive, multi-modal RV assessment - integrating clinical evaluation, biomarkers, echocardiography, cardiac MRI, and right heart catheterization - is crucial for prognosis and monitoring therapy. RV size, function, and tissue characteristics are key indicators.Current management involves PAH-targeted therapies to reduce RV afterload, optimal CTD control, and supportive care. However, CTD-PAH often shows attenuated treatment responses and worse outcomes, emphasizing the need for therapies directly addressing RV maladaptation. Future research priorities include understanding specific RV injury mechanisms in CTD, refining assessment tools, and developing novel RV-directed strategies. Optimizing outcomes requires a deep understanding of RV pathobiology within the CTD context and integrated, multidisciplinary care.