%0 Journal Article %A Christian Gerges %A Mario Gerges %A Pierre Fesler %A Anna Maria Pistritto %A Nicholas P Konowitz %A Johannes Jakowitwsch %A David S Celermajer %A Irene M Lang %T In-depth hemodynamic phenotyping of pulmonary hypertension due to left heart disease %D 2018 %R 10.1183/13993003.00067-2018 %J European Respiratory Journal %P 1800067 %X 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 (Pc'), we partitioned PVR in larger arterial (Rup, upstream resistance) and small arterial plus venous components (Rds, downstream resistance). In the case of small vessel disease, Rup decreases and Rds 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. Rup 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.Cpc-PH is characterized by pre-capillary pulmonary vascular disease and a positive response to inhaled nitric oxideFootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Gerges reports grants from United Therapeutics Corporation, grants from Bayer HealthCare, grants from Actelion Pharmaceuticals, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from AOPOrphan, personal fees from Actelion, outside the submitted work.Conflict of interest: Dr. Gerges reports grants from United Therapeutics Corporation, grants from Bayer HealthCare, grants from Actelion Pharmaceuticals, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from AOPOrphan, personal fees from Actelion, outside the submitted work.Conflict of interest: Dr. Fesler reports personal fees from Actelion, outside the submitted work.Conflict of interest: Dr. Konowitz has nothing to disclose.Conflict of interest: Dr. Celermajer has nothing to disclose.Conflict of interest: Dr. Lang reports grants from United Therapeutics Coroporation, grants from Bayer AG, grants from Actelion Pharamceuticals, during the conduct of the study; grants, personal fees and non-financial support from Actelion , grants, personal fees and non-financial support from AOPOrphan Pharmaceuticals, grants, personal fees and non-financial support from Bayer AG, other from Astra-Zeneca, other from Servier, other from Cordis, other from Medtronic, grants, personal fees and non-financial support from GSK, other from Novartis, grants, personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from United Therapeutics Corporation, outside the submitted work.Conflict of interest: Dr. Jakowitsch has nothing to disclose.Conflict of interest: Dr. Pistritto has nothing to disclose. %U https://erj.ersjournals.com/content/erj/early/2018/03/15/13993003.00067-2018.full.pdf