Mapping right ventricular adaptation in pulmonary arterial hypertension: insights from a six-phenotype model

Abstract Introduction Pulmonary arterial hypertension (PAH) is a progressive disease leading to right ventricular (RV) dysfunction and right heart failure. RV adaptation to increased afterload is a key prognostic factor. Traditional echocardiographic parameters offer insight but may not fully capture RV remodeling complexity. Phenotypic classifications combining RV size, contractility, and ventricular-arterial coupling may improve risk stratification. Methods A multicenter prospective cohort study was conducted in patients with de novo diagnosis of PAH as part of the TREPostinil Subcutáneo a LARgo Plazo en Hipertensión Pulmonar registry (TREPAR-HP). Six right ventricular (RV) phenotypes (A–F) were evaluated based on the RV basal diameter, fractional area change (FAC), and the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). This classification ranges from a normal and adapted RV (phenotypes A–C) to severe dysfunction and dilation (phenotypes D–F). Results Figure 1 shows the distribution of phenotypes. In a cohort of 93 patients (mean age 46.7 years, 86% women), the most common etiology was idiopathic (57%). Most patients presented with functional class III (62.4%) and received dual therapy (86%). Height (p=0.002), right atrial area (p=0.001), RV basal diameter (p0.001), and TAPSE (p0.001) showed significant differences between groups. The median BNP was 290.27 pg/mL, and the average cardiac output was 4.38 L/min (p=0.012). These findings highlight the functional and hemodynamic burden of the cohort. Figure 2 shows the distribution of phenotypes with respect to risk classification according to REVEAL. Conclusion RV phenotypic classification reveals distinct adaptation patterns in PAH. Advanced phenotypes (D–F) showed worse functional class, larger right atrial areas, and greater RV dysfunction. This approach may enhance risk stratification and guide management, underscoring the importance of early detection of RV maladaptation Figure 1. Distribution of phenotypes. Figure 2. distribution of phenotypes with respect to risk classification according to REVEAL.