Abstract
The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD). The current classification system for definitions of PH-LHD is under review. We therefore performed prospective in-depth invasive hemodynamic phenotyping in order to assess the site of increased pulmonary vascular resistance (PVR) in PH-LHD subsets.Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure (P c' ), we partitioned PVR in larger arterial (R up , upstream resistance) and small arterial plus venous components (R ds , downstream resistance). In the case of small vessel disease, R up decreases and R ds increases. Inhaled nitric oxide (iNO) testing was used to assess acute vasoreactivity.Right ventricular (RV) afterload (PVR, pulmonary arterial compliance and effective arterial elastance) was significantly higher in combined post- and pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH, n=20). RV afterload decreased during iNO in Cpc-PH and idiopathic pulmonary arterial hypertension (iPAH, n=31), but remained unchanged in Ipc-PH. R up was similar in Cpc-PH (66.8±10.8%) and iPAH (65.0±12.2%, p=0.530) suggesting small vessel disease, but significantly higher in Ipc-PH (96.5±4.5%, p<0.001) suggesting upstream transmission of elevated left atrial pressures (LAP).RV afterload is driven by elevated LAP in Ipc-PH and is further increased by elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to iNO. Our data support current definitions of PH-LHD subsets.