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The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The ESC/ERS guidelines (published at the end of 2015) and other international recommendations defined pulmonary hypertension (PH) by an invasively measured mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. At the 6 th World Symposium on Pulmonary Hypertension in Nice a modification of this hemodynamic definition in the sense of lowering the threshold to > 20 mmHg was proposed. A pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is additionally required for the diagnosis of pre-capillary PH. This modification must be critically reviewed with regard to the underlying rationale and possible consequences. Therefore, a detailed explanation is required. In particular, it must be made clear that this change currently has no influence on the evidence-based and approval-compliant prescription of drugs for the targeted therapy of pulmonary arterial hypertension (PAH)., Competing Interests: S. Rosenkranz: Honorare für Vorträge und/oder Beratertätigkeiten von Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer und United Therapeutics. Forschungsunterstützung an Institutionen von Actelion, Bayer, Novartis, Pfizer und United Therapeutics. G.P. Diller: Forschungsunterstützung und/oder Konferenz-Teilnahme und/oder Honorare für Vorträge und/oder Beratertätigkeit von Actelion, Pfizer, Daiichi-Sankyo, AOP Orphan Therapeuticals. D. Dumitrescu: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, MSD, Novartis, Pfizer, Servier. Forschungsunterstützung an Institution von Actelion. R. Ewert: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Merck, OMT, Pfizer, United Therapeutics. H.A. Ghofrani: Honorare für Vorträge und/oder Konsultationen von Actelion, Bayer, Gilead, GSK, MSD, Novartis, Pfizer und United Therapeutics. E. Grünig: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, GSK, Novartis, Pfizer und United Therapeutics. M. Halank: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, AOP orphan/OMT, Bayer, Gilead, GSK, MSD, Novartis und Pfizer. M. Held: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, Berlin Chemie, Boehringer, GSK, MSD, Novartis, Pfizer, United Therapeutics. H. Kaemmerer: Forschungsunterstützung und/oder Konferenz-Teilnahme und/oder Honorare für Vorträge und/oder Beratertätigkeit von Actelion, Bayer, Pfizer. H. Klose: Honorare für Vorträge und/oder Beratertätigkeiten und Kongressteilnahmeunterstützung von Actelion, Bayer, MSD, GSK, UT, Novartis, OMT und Pfizer; Forschungsunterstützung von GSK, Actelion und Bayer. G. Kovacs: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, MSD, Novartis, Pfizer, Chiesi, Boehringer-Ingelheim. S. Konstantinides: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, Boehringer. I.M. Lang: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, AOP Orphan, Astra-Zeneca, Bayer-Schering, Cordis, Daiichi-Sankyo, Edwards, GSK, Medtronic, Novartis, Pfizer, Servier, United Therapeutics. T.J. Lange: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, AOP orphan/OMT, Bayer, GSK, Pfizer and United Therapeutics. H. Leuchte: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Merck, und Pfizer. E. Mayer: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, MSD und Pfizer. A. Olschewski: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Bayer, GSK, Pfizer. H. Olschewski: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, Bayer, Belerophon, Boehringer, GSK, Menarini, MSD, Novartis, Pfizer, Roche. K.M. Olsson: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Pfizer und United Therapeutics. C. Opitz: Keine persönlichen Einkünfte als mögliche Interessenkonflikte. R.T. Schermuly: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Bayer, Gilead, MSD, Novartis, United Therapeutics. W. Seeger: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, Bayer, Pfizer, Novartis. H. Wilkens: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, Boehringer-Ingelheim, GSK, MSD, Novartis, Pfizer und Roche. M.M. Hoeper: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, Gilead, GSK, Merck und Pfizer., (© Georg Thieme Verlag KG Stuttgart · New York.)

Abbreviated versions of the risk stratification strategy of the European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines have been recently validated in patients with pulmonary arterial hypertension. We aimed to investigate their prognostic value in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients from the COMPERA registry, which collects six variables of interest (World Health Organization Functional Class, 6-min walk distance, brain natriuretic peptide, right atrial pressure, cardiac index and mixed venous oxygen saturation).We included patients with at least one follow-up visit, no pulmonary endarterectomy and at least three of the six variables available, and classified the patients into low-, intermediate- and high-risk groups. As a secondary analysis, the number of noninvasive low-risk criteria was counted. The association between risk assessment and survival was evaluated.Data from inclusion and follow-up (median 7 months) visits were available for 561 and 231 patients, respectively. Baseline 1- and 5-year survival estimates were significantly different (p<0.0001) in the baseline low-risk (98.6% and 88.3%, respectively), intermediate-risk (94.9% and 61.8%, respectively) and high-risk (75.5% and 32.9%, respectively) cohorts. Follow-up data were even more discriminative, with 100%, 92% and 69% 1-year survival, respectively. The number of low-risk noninvasive criteria was also associated with survival.These analyses suggest that the ESC/ERS risk assessment may be applicable in patients with medically treated CTEPH., Competing Interests: Conflict of interest: M. Delcroix reports research grants, investigator, speaker and consultant fees from Actelion, investigator, speaker and consultant fees from Bayer and GSK, speaker and consultant fees from MSD, investigator fees from Reata and Eli Lilly, and investigator and consultant fees from Bellerophon, outside the submitted work. Conflict of interest: G. Staehler has received speaker's honoraria from Bayer and Actelion, during the conduct of the study. Conflict of interest: H. Gall reports grants and personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer and United Therapeutics, during the conduct of the study. Conflict of interest: E. Grünig reports grants and personal fees from Actelion, Bayer/MSD, grants from GSK, grants from United Therapeutics, grants from Novartis, grants from Actelion, Bayer and MSD, personal fees from SCOPE, OrPha Swiss GmbH and Zurich Heart House, outside the submitted work. Conflict of interest: M. Held reports research grants and other from Actelion, honoraria for lectures from Actelion, Bayer Healthcare, Berlin Chemie, Boehringer Ingelheim, GSK, MSD, Novartis and Pfizer, participation in clinical trials for Actelion, Bayer, GSK, Pfizer and United Therapeutics, and honoraria for advisory board work from Actelion, Bayer, Boehringer, GSK and MSD, outside the submitted work. Conflict of interest: M. Halank reports personal fees and nonfinancial support from Actelion, Bayer, GSK, MSD, Novartis and OMT, outside the submitted work. Conflict of interest: H. Klose reports grants and personal fees from Bayer and Actelion, and personal fees from GSK, United Therapeutics and MSD, outside the submitted work. Conflict of interest: A. Vonk-Noordegraaf reports grants from NWO-VICI, speaker fees from Actelion and consultation fees from Arena, outside the submitted work. Conflict of interest: S. Rosenkranz reports grants and personal fees for speaking/consulting from Actelion, Bayer, Pfizer, Novartis and United Therapeutics, personal fees for speaking/consulting from GSK, Gilead and MSD, during the conduct of the study. Conflict of interest: J. Pepke-Zaba reports grants (compensation for data entry) from the COMPERA registry during the conduct of the study; grants, personal fees and nonfinancial support from Actelion, Bayer and Merck, outside the submitted work. Conflict of interest: C.F. Opitz reports other from Actelion, Bayer and MSD, outside the submitted work. Conflict of interest: J.S.R. Gibbs reports grants and personal fees from Actelion, Bayer, GSK and MSD, personal fees from Arena, Bellerophon and Pfizer, and grants from United Therapeutics, during the conduct of the study. Conflict of interest: T.J. Lange reports grants (compensation for data entry) from the COMPERA registry, during the conduct of the study; grants, personal fees and nonfinancial support from Actelion, Bayer, GSK and Pfizer, personal fees and nonfinancial support from AOP Orphan Pharmaceuticals and MSD, and grants and personal fees from United Therapeutics, outside the submitted work. Conflict of interest: I. Tsangaris reports grants, personal fees and nonfinancial support from Actelion, GSK and Bayer, and personal fees and nonfinancial support from MSD and United Therapeutics, outside the submitted work. Conflict of interest: D. Huscher reports personal fees from Actelion, outside the submitted work. Conflict of interest: D. Pittrow reports personal fees from Actelion, Bayer, Aspen, Boehringer Ingelheim, AstraZeneca and MSD, outside the submitted work. Conflict of interest: K.M. Olsson reports personal fees for lectures from Actelion, Bayer, GSK, Pfizer and United Therapeutics, outside the submitted work. Conflict of interest: M.M. Hoeper reports personal fees for lectures and consultations from Actelion, Bayer, Gilead, GSK, MSD and Pfizer, outside the submitted work., (Copyright ©ERS 2018.)