Non-invasive surrogate of main pulmonary artery stiffness is associated with right ventricular function in experimental pulmonary arterial hypertension

Main pulmonary artery (MPA) stiffening increases right ventricular (RV) afterload and is associated with worse outcomes in pulmonary arterial hypertension (PAH). Measures of pulmonary artery compliance (PAC) and vascular resistance (PVR) require invasive catheterization, limiting clinical application. Echocardiographic assessment of MPA pulsatility, the relative change in MPA diameter, may be useful but not well validated. We investigated the relationship between MPA pulsatility and passive stiffness, PAC, PVR, RV function, and RV-PA coupling in sugen-hypoxia (SuHx) rats and children with idiopathic PAH (iPAH) and controls. Groups of 3-week and 6-week SuHx rats and controls underwent echocardiography and invasive catheterization to characterize progressive changes in MPA pulsatility, PAC, PVR, and RV function. Harvested MPAs underwent biaxial tensile testing to determine its passive stiffness. RV echo function and MPA pulsatility were retrospectively analyzed in iPAH patients and healthy subjects. PAH rats and iPAH patients had reduced MPA pulsatility (23±7.9% at 3-weeks and 18±5.0% at 6-weeks SuHx; 14.5(7.7) in iPAH) compared to controls (40±7% at 3-weeks and 31±6% at 6-weeks in healthy controls; 30.8(6.9) in healthy subjects). Reduced MPA pulsatility correlated with increased high-strain circumferential passive stiffness (r=-0.88, p<0.0001), reduced PAC (r=0.78, p<0.0001), increasing PVRi (r²=0.47, p<0.0001), RV dysfunction and impaired coupling in PAH rats. MPA pulsatility in iPAH and healthy subjects was inversely related to RV size and positively linearly related to RV systolic function. Our results suggest that MPA pulsatility is an accessible measure of MPA stiffness, expanding the assessment of RV afterload and RV-PA coupling in PAH.

echocardiography; pediatrics; pulmonary arterial hypertension; pulmonary artery; right ventricular function.