COPD is frequently associated with mild to moderate pulmonary hypertension (PH). However, a small subset of patients develops severe PH, which is currently haemodynamically defined as mean pulmonary arterial pressure (mPAP) ⩾35 mmHg, or mPAP ⩾25 mmHg in combination with cardiac index <2.0 L•min −1 •m −2 [1, 2]. These cut-offs are, however, arbitrary and mainly based on expert opinion. In this study we aimed to determine prognostically relevant haemodynamic thresholds for severe PH in COPD by using an unbiased approach.We retrospectively analysed COPD patients with at least 1-year follow-up who underwent right heart catheterisation (RHC) and clinical evaluation at our clinic due to suspected PH between 2003 and 2018. RHC was performed in the supine position, with a mid-thoracic zero reference level, as previously described [3]. All data were included into a prospective local database (GRAPHIC (GRAz Pulmonary Hypertension In COPD) registry). Patients undergoing lung transplantation at any time (n=3) were excluded from this analysis. We performed Cox regression analysis, adjusting for age, sex and forced expiratory volume in 1 s (FEV 1 ) with the primary outcome all-cause mortality. For identification of the best prognostic cut-offs, we searched for the lowest p-values. Continuous baseline characteristics of the groups according to the best cut-off were compared using independent t-tests or Mann-Whitney U-test, as appropriate. Continuous variables are described as mean±SD or median (interquartile range), as appropriate. The study was approved by the institutional ethics board (EK: 32-180 ex 19/20) of the Medical University Graz.We included 139 COPD patients (age 68 (62-73) years; 55.4% male; mPAP 35 (27-43) mmHg; pulmonary vascular resistance (PVR) 4.3 (2.9-7.3) WU; FEV 1 56±20% predicted). 72 patients (52%) died during a follow-up of 8.0 (3.8-11.7) years, with a median time to death of 3.0 (1.3-5.2) years. 61 (44%) patients received any PAH drug at any time-point.Out of the examined haemodynamic parameters, after adjustment for age, sex and FEV 1 , PVR (HR 1.09, 95% CI 1.02-1.16; p=0.007) and mPAP (HR 1.03, 95% CI 1.01-1.05; p=0.001) were associated with survival, while pulmonary arterial wedge pressure (PAWP) and cardiac index were not ( p=0.696 and p=0.171). Among all haemodynamic parameters, PVR >5.0 WU was the best prognostic cut-off (HR 2.59, 95% CI 1.58-4.27; p<0.001) (figure 1a). Patients with PVR >5.0 WU were more frequently males ( p<0.001) and had a lower 6-min walk distance (254±112 versus 333±117 m; p<0.001), lower peak oxygen uptake (41±13 versus 61±23% predicted; p<0.001) and higher N-terminal pro brain natriuretic peptide (2288 (694-3634) versus 442 (160-1126) pg•mL −1 ; p<0.001) as compared to patients with PVR ⩽5.0 WU.For mPAP, the p-values for potential cut-off scores showed two equivalent minimal levels, the first at 33 mmHg (HR 2.26, 95% CI 1.37-3.71; p=0.001) (figure 1b) and the second at 45 mmHg (HR 2.44, 95% CI 1.43-4.16; p=0.001). Out of the patients with mPAP ⩾33 mmHg, n=28 (36%) and n=49 ...

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