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Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry

Marius M. Hoeper, Christine Pausch, Ekkehard Grünig, Gerd Staehler, Doerte Huscher, David Pittrow, Karen M. Olsson, Carmine Dario Vizza, Henning Gall, Oliver Distler, Christian Opitz, J. Simon R. Gibbs, Marion Delcroix, H. Ardeschir Ghofrani, Stephan Rosenkranz, Da-Hee Park, Ralf Ewert, Harald Kaemmerer, Tobias J. Lange, Hans-Joachim Kabitz, Dirk Skowasch, Andris Skride, Martin Claussen, Juergen Behr, Katrin Milger, Michael Halank, Heinrike Wilkens, Hans-Jürgen Seyfarth, Matthias Held, Daniel Dumitrescu, Iraklis Tsangaris, Anton Vonk-Noordegraaf, Silvia Ulrich, Hans Klose
European Respiratory Journal 2022 59: 2102024; DOI: 10.1183/13993003.02024-2021
Marius M. Hoeper
1Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany
2Member of the German Center for Lung Research (DZL), Hannover, Germany
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  • ORCID record for Marius M. Hoeper
  • For correspondence: hoeper.marius@mh-hannover.de
Christine Pausch
3GWT-TUD GmbH, Epidemiological Centre, Dresden, Germany
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Ekkehard Grünig
2Member of the German Center for Lung Research (DZL), Hannover, Germany
4Centre for Pulmonary Hypertension, Thoraxclinic Heidelberg GmbH at Heidelberg University Hospital, Heidelberg, Germany
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Gerd Staehler
5Lungenklinik, Löwenstein, Germany
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Doerte Huscher
6Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany
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David Pittrow
3GWT-TUD GmbH, Epidemiological Centre, Dresden, Germany
7Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany
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Karen M. Olsson
1Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany
2Member of the German Center for Lung Research (DZL), Hannover, Germany
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Carmine Dario Vizza
8Dept of Cardiovascular and Respiratory Diseases, Sapienza, University of Rome, Rome, Italy
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Henning Gall
2Member of the German Center for Lung Research (DZL), Hannover, Germany
9Dept of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
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Oliver Distler
10Dept of Rheumatology, University Hospital, Zurich, Switzerland
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Christian Opitz
11Dept of Cardiology, DRK Kliniken Berlin Westend, Berlin, Germany
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J. Simon R. Gibbs
12Dept of Cardiology, National Heart and Lung Institute, Imperial College London, London, UK
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Marion Delcroix
13Clinical Dept of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Dept of Chronic Diseases and Metabolism (CHROMETA), KU Leuven – University of Leuven, Leuven, Belgium
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H. Ardeschir Ghofrani
2Member of the German Center for Lung Research (DZL), Hannover, Germany
9Dept of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
14Dept of Medicine, Imperial College London, London, UK
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Stephan Rosenkranz
15Clinic III for Internal Medicine (Cardiology) and Center for Molecular Medicine (CMMC), and the Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
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Da-Hee Park
1Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany
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Ralf Ewert
16Dept of Respiratory Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
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Harald Kaemmerer
17Deutsches Herzzentrum München, Klinik für Angeborene Herzfehler und Kinder Kardiologie, TU München, Munich, Germany
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Tobias J. Lange
18Dept of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany
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Hans-Joachim Kabitz
19Medizinische Klinik II, Gemeinnützige Krankenhausbetriebsgesellschaft Konstanz mbH, Konstanz, Germany
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Dirk Skowasch
20Medizinische Klinik und Poliklinik II, Innere Medizin – Kardiologie/Pneumologie, Universitätsklinikum Bonn, Bonn, Germany
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Andris Skride
21VSIA Pauls Stradins Clinical University Hospital, Riga Stradins University, Riga, Latvia
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Martin Claussen
22Fachabteilung Pneumologie, LungenClinic Grosshansdorf, Grosshansdorf, Germany
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Juergen Behr
23Comprehensive Pneumology Center, Lungen Forschungsambulanz, Helmholtz Zentrum, Munich, Germany
24Dept of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany
25Member of the German Center for Lung Research (DZL), Munich, Germany
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Katrin Milger
24Dept of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany
25Member of the German Center for Lung Research (DZL), Munich, Germany
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Michael Halank
26Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Dresden, Germany
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Heinrike Wilkens
27Klinik für Innere Medizin V, Pneumologie, Universitätsklinikum des Saarlandes, Homburg, Germany
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Hans-Jürgen Seyfarth
28Medizinische Klinik und Poliklinik II, Abteilung für Pneumologie, Universitätsklinikum Leipzig, Leipzig, Germany
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Matthias Held
29Dept of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Würzburg, Germany
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Daniel Dumitrescu
30Clinic for General and Interventional Cardiology and Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
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Iraklis Tsangaris
312nd Critical Care Dept, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Anton Vonk-Noordegraaf
32Dept of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Silvia Ulrich
33Clinic of Pulmonology, University and University Hospital of Zurich, Zurich, Switzerland
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Hans Klose
34Dept of Respiratory Medicine, Eppendorf University Hospital, Hamburg, Germany
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  • FIGURE 1
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    FIGURE 1

    STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) diagram showing eligibility for analysis. PAH: pulmonary arterial hypertension; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary arterial wedge pressure. #: more than one reason for exclusion could apply.

  • FIGURE 2
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    FIGURE 2

    Kaplan–Meier survival estimates overall and by pulmonary arterial hypertension (PAH) subtype. CHD: congenital heart disease; POPH: porto-pulmonary hypertension; I/H/D: idiopathic/heritable/drug-associated; CTD: connective tissue disease.

  • FIGURE 3
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    FIGURE 3

    Temporal trends in the use of initial combination therapy and combination therapy 1 year after pulmonary arterial hypertension diagnosis in a) the entire cohort, and in the subgroups of patients aged b) <65 years and c) ≥65 years.

  • FIGURE 4
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    FIGURE 4

    Annualised survival rates (95% CI) at 1 and 3 years after pulmonary arterial hypertension (PAH) diagnosis in a) the entire cohort, and in the subgroups of patients aged b) <65 years and c) ≥65 years. The black and red numbers indicate the numbers of patients available for the annualised 1- and 3-year survival rates, respectively.

Tables

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  • TABLE 1

    Baseline characteristics of patients newly diagnosed with pulmonary arterial hypertension (PAH) between 2010 and 2019

    All PAHI/H/D-PAHCTD-PAHCHD-PAHHIV-PAHPOPH
    Patients2531 (100)1698 (67.1)536 (21.2)128 (5.1)24 (0.9)145 (5.7)
    Age, years64.6±15.865.9±15.966.3±13.150.6±18.145.8±12.157.8±11.7
    Female1609 (63.6)1016 (59.8)434 (81.0)84 (65.6)11 (45.8)64 (44.1)
    BMI, kg·m−228.0±6.128.4±6.126.7±5.426.3±6.527.6±8.229.6±6.2
    WHO FC
     I15 (0.6)7 (0.4)2 (0.4)4 (3.5)1 (4.2)1 (0.7)
     II373 (15.7)244 (15.3)78 (15.4)26 (22.8)6 (25.0)19 (13.8)
     III1675 (70.4)1117 (69.9)369 (73.1)73 (64.0)14 (58.3)102 (73.9)
     IV315 (13.2)229 (14.3)56 (11.1)11 (9.6)3 (12.5)16 (11.6)
    6MWD, m297.1±127.1297.4±127.3278.4±124.2344.6±112.9366.0±146.7310.7±129.1
    Pulmonary function
     TLC, % pred89.6±17.491.7±16.484.0±18.884.0±15.288.7±11.594.7±16.9
     FVC, % pred80.1±20.380.4±20.080.0±21.570.2±18.585.5±10.682.5±19.1
     FEV1, % pred76.4±19.876.5±20.076.9±19.666.0±16.985.0±15.378.8±19.6
     DLCO, % pred50.5±21.752.1±22.642.6±17.065.8±18.947.0±17.557.9±17.8
     PaO2, mmHg65.0±12.364.5±12.665.2±12.066.0±10.169.8±19.368.9±10.8
     PaCO2, mmHg35.1±6.535.6±6.434.3±6.835.9±6.035.2±1.333.0±5.9
    Smoking history
     Current96 (6.9)76 (6.6)5 (3.3)3 (10.0)0 (0.0)12 (25.5)
     Former594 (43.0)490 (42.6)66 (43.7)13 (43.3)2 (50.0)23 (48.9)
     Never693 (50.1)585 (50.8)80 (53.0)14 (46.7)2 (50.0)12 (25.5)
     Pack-years#30.0 (15.0–40.0)30.0 (15.0–45.0)20.0 (10.0–30.0)12.5 (10.0–28.8)NA (NA–NA)20.0 (20.0–37.5)
    Comorbid conditions
     Obesity¶810 (32.7)589 (35.1)120 (23.7)34 (26.6)6 (28.6)61 (42.4)
     Hypertension1329 (60.7)1007 (65.6)225 (56.0)36 (32.4)7 (46.7)54 (43.2)
     Coronary heart disease554 (26.1)435 (29.0)89 (23.2)10 (9.3)1 (6.7)19 (15.8)
     Diabetes mellitus590 (27.2)489 (32.1)61 (15.5)18 (16.2)0 (0.0)22 (17.5)
    Haemodynamics
     RAP, mmHg8.3±4.88.3±4.77.8±4.98.6±5.58.3±4.19.8±5.3
     mPAP, mmHg44.2±12.944.3±12.741.3±11.550.8±19.147.0±11.447.4±10.8
     PAWP, mmHg9.5±3.49.5±3.39.3±3.49.6±3.67.9±3.09.7±3.5
     CI, L·min−1·m−22.3±0.82.2±0.82.4±0.82.8±1.22.3±1.02.7±1.1
     PVR, dyn·s·cm−5742.7±402.4764.8±412.5675.5±353.8789.4±511.0871.2±348.3669.7±321.6
     PVR, WU9.3±5.09.6±5.28.4±4.49.9±6.410.9±4.48.4±4.0
     SvO2, %62.8±8.662.3±8.563.5±8.765.4±10.157.2±7.764.5±7.5
    Laboratory findings
     Creatinine, µmol·L−1101.7±55.3106.1±60.295.3±41.986.5±50.983.0±24.689.1±33.9
     Uric acid, µmol·L−1436.6±151.6443.1±146.5430.2±154.1393.6±188.6383.3±123.1424.8±161.6
     Bilirubin, µmol·L−115.6±14.214.7±11.812.9±12.216.5±21.632.0±34.629.5±20.0
     NT-proBNP, pg·mL−11454 (480–3341)1574 (566–3498)1504 (432–3430)513 (262–1163)1212 (209–2542)848 (233–2128)
     BNP, pg·mL−1206 (94–497)200 (102–462)231 (78–636)154 (62–315)175 (150–201)240 (143–454)
    Risk
     Low246 (9.8)153 (9.1)49 (9.2)22 (17.6)6 (25.0)16 (11.0)
     Intermediate1698 (67.6)1144 (67.8)349 (65.8)91 (72.8)15 (62.5)99 (68.3)
     High568 (22.6)391 (23.2)132 (24.9)12 (9.6)3 (12.5)30 (20.7)

    Data are presented as n (%), mean±sd or median (interquartile range). I/D/H: idiopathic/drug-associated/heritable; CTD: connective tissue disease; CHD: congenital heart disease; POPH: porto-pulmonary hypertension; BMI: body mass index; WHO FC: World Health Organization Functional Class; 6MWD: 6-min walk distance; TLC: total lung capacity; FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; DLCO: diffusing capacity of the lung for carbon monoxide; PaO2: arterial oxygen tension; PaCO2: arterial carbon dioxide tension; RAP: right atrial pressure; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary arterial wedge pressure; CI: cardiac index; PVR: pulmonary vascular resistance; SvO2: mixed venous oxygen saturation; NT-proBNP: N-terminal fragment of pro-brain natriuretic peptide; BNP: brain natriuretic peptide. #: if current or former smoker; ¶: BMI ≥30 kg·m−2.

    • TABLE 2

      Use of drugs to treat pulmonary arterial hypertension (PAH) within 3 months and 1, 2 and 3 years (±6 months) after diagnosis

      3 months (n=2375)1 year (n=2136)2 years (n=1727)3 years (n=1299)
      No therapy8 (0.3)73 (3.4)61 (3.5)48 (3.7)
      Monotherapy1901 (80.0)1146 (53.7)841 (48.7)604 (46.5)
       ERA401 (21.1)223 (19.5)145 (17.2)99 (16.4)
       PDE5i1375 (72.3)851 (74.3)642 (76.3)467 (77.3)
       sGC63 (3.3)40 (3.5)31 (3.7)23 (3.8)
       PCA6 (0.3)3 (0.3)1 (0.1)1 (0.2)
        PCA oral or inhaled#1 (16.7)2 (66.7)1 (100.0)0 (0.0)
        PCA i.v. or s.c.¶5 (83.3)1 (33.3)0 (0.0)1 (100.0)
       CCB51 (2.7)29 (2.5)22 (2.6)14 (2.3)
       Other PAH treatment5 (0.3)0 (0.0)0 (0.0)0 (0.0)
      Combination therapy466 (19.6)917 (42.9)825 (47.8)647 (49.8)
       ERA+PDE5i320 (68.7)619 (67.5)539 (65.3)400 (61.8)
       Other than ERA+PDE5i146 (31.3)298 (32.5)286 (34.7)247 (38.2)
        ERA+PDE5i+PCA33 (22.6)106 (35.6)110 (38.5)104 (42.1)
      ­­  Triple combination therapy including i.v. or s.c. PCA+21 (14.4)44 (14.8)47 (16.4)45 (18.2)

      Data are presented as n (%); percentages refer to subgroups only, if applicable. ERA: endothelin receptor antagonist; PDE5i: phosphodiesterase-5 inhibitor; sGC: soluble guanylate cyclase stimulator; PCA: prostacyclin analogue; CCB: calcium channel blocker. #: selexipag, iloprost inhaled, treprostinil inhaled, beraprost; ¶: epoprostenol, iloprost i.v., treprostinil i.v./s.c.; +: all triple combination therapies that include i.v. or s.c. PCA therapy.

      • TABLE 3

        Estimated survival probability at 1 and 3 years in patients diagnosed with pulmonary arterial hypertension (PAH) between 2010 and 2014 and between 2015 and 2019

        2010–20142015–2019
        1-year survival3-year survival1-year survival3-year survival
        Entire cohort89.0 (87.2–90.9)67.8 (65.0–70.8)90.8 (89.3–92.4)70.5 (67.8–73.4)
        Patients aged <65 years93.3 (91.1–95.5)80.0 (76.4–83.8)96.0 (94.3–97.8)83.4 (79.7–87.2)
        Patients aged ≥65 years85.5 (82.8–88.4)58.1 (54.2–62.3)87.7 (85.5–90.0)63.1 (59.5–66.9)
        I/H/D-PAH90.2 (88.0–92.5)69.4 (66.0–73.0)90.8 (89.0–92.7)70.4 (67.1–73.8)
        CTD-PAH85.3 (81.0–89.9)57.4 (51.3–64.3)88.2 (84.3–92.2)67.1 (60.9–74.0)
        I/H/D-PAH with no comorbidities and DLCO >45% predicted90.7 (82.4–99.8)86.0 (76.2–97.0)97.5 (94.2–100.0)90.1 (82.6–98.2)

        Data are presented as mean % (95% CI). I/H/D: idiopathic/heritable/drug-associated; CTD: connective tissue disease; DLCO: diffusing capacity of the lung for carbon monoxide.

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        Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry
        Marius M. Hoeper, Christine Pausch, Ekkehard Grünig, Gerd Staehler, Doerte Huscher, David Pittrow, Karen M. Olsson, Carmine Dario Vizza, Henning Gall, Oliver Distler, Christian Opitz, J. Simon R. Gibbs, Marion Delcroix, H. Ardeschir Ghofrani, Stephan Rosenkranz, Da-Hee Park, Ralf Ewert, Harald Kaemmerer, Tobias J. Lange, Hans-Joachim Kabitz, Dirk Skowasch, Andris Skride, Martin Claussen, Juergen Behr, Katrin Milger, Michael Halank, Heinrike Wilkens, Hans-Jürgen Seyfarth, Matthias Held, Daniel Dumitrescu, Iraklis Tsangaris, Anton Vonk-Noordegraaf, Silvia Ulrich, Hans Klose
        European Respiratory Journal Jun 2022, 59 (6) 2102024; DOI: 10.1183/13993003.02024-2021

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        Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry
        Marius M. Hoeper, Christine Pausch, Ekkehard Grünig, Gerd Staehler, Doerte Huscher, David Pittrow, Karen M. Olsson, Carmine Dario Vizza, Henning Gall, Oliver Distler, Christian Opitz, J. Simon R. Gibbs, Marion Delcroix, H. Ardeschir Ghofrani, Stephan Rosenkranz, Da-Hee Park, Ralf Ewert, Harald Kaemmerer, Tobias J. Lange, Hans-Joachim Kabitz, Dirk Skowasch, Andris Skride, Martin Claussen, Juergen Behr, Katrin Milger, Michael Halank, Heinrike Wilkens, Hans-Jürgen Seyfarth, Matthias Held, Daniel Dumitrescu, Iraklis Tsangaris, Anton Vonk-Noordegraaf, Silvia Ulrich, Hans Klose
        European Respiratory Journal Jun 2022, 59 (6) 2102024; DOI: 10.1183/13993003.02024-2021
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