Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:39

Article

Hoeper, Marius M.^1,2  Pausch, Christine³  Gruenig, Ekkehard⁴  Klose, Hans⁵  Staehler, Gerd⁶  Huscher, Doerte⁷  Pittrow, David^3,8  Olsson, Karen M.^1,2  Vizza, Carmine Dario⁹  Gall, Henning^2,10  Benjamin, Nicola⁴  Distler, Oliver¹¹  Opitz, Christian¹²  Gibbs, J. Simon R.¹³  Delcroix, Marion¹⁴  Ghofrani, H. Ardeschir^1,10,15  Rosenkranz, Stephan^16,17,18  Ewert, Ralf¹⁹  Kaemmerer, Harald²⁰  Lange, Tobias J.²¹  Kabitz, Hans-Joachim²²  Skowasch, Dirk²³  Skride, Andris²⁴  Jureviciene, Elena²⁵  Paleviciute, Egle²⁵  Miliauskas, Skaidrius²⁶  Claussen, Martin²⁷  Behr, Juergen^28,29,30  Milger, Katrin²⁹  Halank, Michael³¹  Wilkens, Heinrike³²  Wirtz, Hubert³³  Pfeuffer-Jovic, Elena³⁴  Harbaum, Lars⁵  Scholtz, Werner³⁵  Dumitrescu, Daniel³⁵  Bruch, Leonhard³⁶  Coghlan, Gerry³⁷  Neurohr, Claus³⁸  Tsangaris, Iraklis³⁹  Gorenflo, Matthias⁴⁰  Scelsi, Laura⁴¹  Vonk-Noordegraaf, Anton⁴²  Ulrich, Silvia⁴³  Held, Matthias³⁵ 

[1] Hannover Med Sch, Dept Resp Med, D-30623 Hannover, Germany

[2] German Ctr Lung Res DZL, Hannover, Germany

[3] GWT TUD GmbH, Epidemiol Ctr, Dresden, Germany

[4] Heidelberg Univ Hosp, Ctr Pulm Hypertens, Thoraxclin Heidelberg GmbH, Heidelberg, Germany

[5] Eppendorf Univ Hosp, Dept Resp Med, Hamburg, Germany

[6] Lungenklinik, Lowenstein, Germany

[7] Charite, Inst Biometry & Clin Epidemiol, Berlin, Germany

[8] Tech Univ Dresden, Med Fac, Inst Clin Pharmacol, Dresden, Germany

[9] Sapienza Univ Rome, Dept Cardiovasc & Resp Dis, Rome, Italy

[10] Justus Liebig Univ Giessen, Univ Giessen & Marburg Lung Ctr UGMLC, Dept Internal Med, Giessen, Germany

[11] Univ Hosp, Dept Rheumatol, Zurich, Switzerland

[12] DRK Kliniken Berlin Westend, Dept Cardiol, Berlin, Germany

[13] Imperial Coll London, Natl Heart & Lung Inst, Dept Cardiol, London, England

[14] Univ Hosp Leuven, Dept Pneumol, Leuven, Belgium

[15] Imperial Coll, Dept Med, London, England

[16] Univ Cologne, Clin Internal Med Cardiol 3, Cologne, Germany

[17] Univ Cologne, Ctr Mol Med, Cologne, Germany

[18] Univ Cologne, Cologne Cardiovasc Res Ctr CCRC, Cologne, Germany

[19] Ernst Moritz Arndt Univ Greifswald, Dept Resp Med, Greifswald, Germany

[20] Tech Univ Munich, Deutsch Herzzentrum Munchen, Klin Angeborene Herzfehler & Kinderkardiol, Munich, Germany

[21] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany

[22] Gemeinnutzige Krankenhausbetriebsgesell Konstanz, Med Klin 2, Constance, Germany

[23] Univ Klinikum Bonn, Med Klin & Poliklin 2, Innere Med Kardiol Pneumol, Bonn, Germany

[24] Riga Stradin Univ, VSIA Pauls Stradins Clin Univ Hosp, Riga, Latvia

[25] Vilnius Univ, Vilnius Univ Hosp Santaros Klin, Referral Ctr Pulm Hypertens, Fac Med, Vilnius, Lithuania

[26] Lithuanian Univ Hlth Sci, Hosp Lithuanian Univ Hlth Sci, Pulm Hypertens Ctr, Dept Pulmonol, Kaunas, Lithuania

[27] LungenClin Grosshansdorf, Fachabt, Pneumol, Grosshansdorf, Germany

[28] Helmholtz Zentrum, Comprehens Pneumol Ctr, Lungenforschungsambulanz, Munich, Germany

[29] Ludwig Maximilians Univ Munchen, Comprehens Pneumol Ctr Munich CPC M, German Ctr Lung Res DZL, Dept Internal Med 5, Munich, Germany

[30] Asklepios Fachkliniken Munchen Gauting, Dept Resp Med, Munich, Germany

[31] Univ Klinikum Carl Gustav Carus Tech Univ Dresden, Med Klin & Poliklin 1, Dresden, Germany

[32] Univ Klinikum Univ Kliniken Saarlandes, Pneumol, Klin Innere Med, Homburg, Germany

[33] Uni Klinikum Leipzig, Med Klin & Poliklin 1, Abt Pneumol, Leipzig, Germany

[34] Cent Clin Wurzburg, Dept Internal Med Resp Med & Ventilatory Support, Med Mission Hosp, Wurzburg, Germany

[35] Ruhr Univ Bochum, Herz & Diabet Zentrum NRW, Clin Gen & Intervent Cardiol & Angiol, Bad Oeynhausen, Germany

[36] Unfallkrankenhaus Berlin, Klin Innere Med Kardiol, Berlin, Germany

[37] Royal Free Hosp, Cardiol, London, England

[38] Klin Schillerhohe, Abt Pneumol & Beatmungsmed, Gerlingen, Germany

[39] Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Crit Care Dept 2, Athens, Greece

[40] Univ Klinikum Heidelberg, Klin Angeborene Herzfehler & Kinderkardiol, Heidelberg, Germany

[41] Fdn IRCCS Policlin San Matteo, Div Cardiol, Pavia, Italy

[42] Vrije Univ Amsterdam, Dept Pulm Med, Amsterdam UMC, Amsterdam Cardiovasc Sci, Amsterdam, Netherlands

[43] Univ Hosp Zurich, Clin Pulmonol, Zurich, Switzerland

关键词: pulmonary arterial hypertension;    phenotypes;    cluster;    survival;    mortality;   

DOI  :  10.1016/j.healun.2020.09.011

来源: Elsevier

【 摘 要 】

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with 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, presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). 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 monary 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, 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 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, 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 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified tinct phenotypes, which differed in clinical presentation, response to therapy, and survival. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

【 授权许可】

Free