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Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy

Mari Nishizaki, Aiko Ogawa, Hiromi Matsubara
ERJ Open Research 2021 7: 00725-2020; DOI: 10.1183/23120541.00725-2020
Mari Nishizaki
1Dept of Rehabilitation, National Hospital Organization Okayama Medical Center, Okayama, Japan
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Aiko Ogawa
2Dept of Clinical Science, National Hospital Organization Okayama Medical Center, Okayama, Japan
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  • ORCID record for Aiko Ogawa
Hiromi Matsubara
2Dept of Clinical Science, National Hospital Organization Okayama Medical Center, Okayama, Japan
3Dept of Cardiology, National Hospital Organization Okayama Medical Center, Okayama, Japan
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  • ORCID record for Hiromi Matsubara
  • For correspondence: matsubara.hiromi@gmail.com
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  • FIGURE 1
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    FIGURE 1

    Flow diagram of patient population for study inclusion. PAH: pulmonary arterial hypertension.

  • FIGURE 2
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    FIGURE 2

    Haemodynamic and oxygen parameters during cardiopulmonary exercise testing in patients with pulmonary arterial hypertension. a) mean pulmonary arterial pressure (mPAP); b) cardiac index; c) total pulmonary resistance (TPR); d) peripheral arterial oxygen saturation (SpO2).

  • FIGURE 3
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    FIGURE 3

    The mean pulmonary arterial pressure (mPAP)/cardiac output slope during cardiopulmonary exercise testing in patients with pulmonary arterial hypertension. The broken line represents mPAP at rest of 30 mmHg and the dotted line represents the mPAP/cardiac output slope of 3 mmHg·min·L−1.

  • FIGURE 4
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    FIGURE 4

    Correlation between the mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope and parameters during cardiopulmonary exercise testing in patients with pulmonary arterial hypertension. a) Minute ventilation (V′E)/carbon dioxide output (V′CO2) slope; b) peripheral arterial oxygen saturation (SpO2)/workload slope. The continuous lines indicate the regression lines.

Tables

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  • TABLE 1

    Patient characteristics

    BaselineStudy enrolmentp-value
    Male/female3/29
    Age years28.5±10.333.0±10.1<0.01
    Body mass index kg·m−220.7±3.019.8±2.60.09
    WHO functional class# (I/II/III/IV)III (0/6/14/12)II (7/25/0/0)<0.01
    PAH-specific therapy
     Intravenous epoprostenol1 (3)26 (81)<0.01
     Beraprost11 (34)5 (16)0.18
     Endothelin receptor antagonist9 (28)30 (94)<0.01
     Phosphodiesterase type 5 inhibitor6 (19)21 (66)<0.01
     Soluble guanylate cyclase stimulator0 (0)1 (3)
     Combination therapy
      Dual therapy2 (6)13 (41)<0.01
      Triple therapy4 (13)19 (59)<0.01
    Laboratory parameters
     BNP pg·mL−1334.5 (8.7–1687.6)10.3 (5.8–131.7)<0.01
    Respiratory parameters
     Vital capacity % predicted89.9±17.293.7±14.40.03
     FEV1/FVC %84.1±7.382.5±7.20.24
     DLCO % predicted58.5±12.666.3±10.8<0.01
    Pulmonary haemodynamic parameters
     PAWP mmHg8.3±3.47.9±3.20.57
     mPAP mmHg61.8±18.328.7±12.2<0.01
     Cardiac index L·min−1·m−22.17±0.663.59±0.89<0.01
     PVR Wood units18.3±8.04.3±2.9<0.01
    Exercise capacity
     6MWD m287.3±117.1449.7±69.2<0.01

    Data are presented as n, mean±sd, n (%) or median (range), unless otherwise stated. WHO: World Health Organization; PAH: pulmonary arterial hypertension; BNP: brain natriuretic peptide; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; PAWP: pulmonary artery wedge pressure; mPAP: mean pulmonary arterial pressure; PVR: pulmonary vascular resistance; 6MWD: 6-min walk distance. #: median (n).

    • TABLE 2

      Haemodynamic and oxygen parameters during cardiopulmonary exercise testing

      RestPeak exerciseChangep-value
      sBP mmHg104.0±10.4127.8±19.4+23<0.01
      Heart rate bpm82.4±12.0121.9±14.7+50<0.01
      mRAP mmHg3.6±2.06.4±2.2+121<0.01
      mPAP mmHg27.9±10.745.9±16.7+67<0.01
      Cardiac index L·min−1·m−23.72±0.855.35±1.20+46<0.01
      TPR Wood units5.74±3.426.58±3.82+17<0.01
      SpO2 %97.0±1.294.0±2.7−3.1<0.01
      SvO2 %76.8±4.253.5±7.6−30<0.01

      Data are presented as mean±sd or %. sBP: systolic blood pressure; mRAP: mean right atrial pressure; mPAP: mean pulmonary arterial pressure; TPR: total pulmonary resistance; SpO2: peripheral arterial oxygen saturation; SvO2: mixed venous oxygen saturation.

      • TABLE 3

        Respiratory parameters during cardiopulmonary exercise testing

        Peak V′O2 mL·min−1658.5±147.8
        Peak V′O2/weight mL·min−1·kg−114.3±3.7
        Peak V′O2/weight % predicted53.8±13.5
        V′O2 at AT mL·min−1533.3±106.0
        V′O2 at AT/weight mL·min−1·kg−111.6±2.5
        V′O2 at AT/weight % predicted70.8±15.4
        V′E/V′CO2 slope mL·mL−131.7±5.2

        Data are presented as mean±sd. V′O2: oxygen uptake; AT: anaerobic threshold; V′E: minute ventilation; V′CO2: carbon dioxide output.

        • TABLE 4

          Correlation between the mean pulmonary arterial pressure (mPAP)/cardiac output slope and parameters at rest and during the exercise

          rp-value
          At rest
           mPAP0.73<0.01
           Cardiac index−0.150.41
           TPR0.64<0.01
           SpO2−0.030.89
           SvO2−0.150.42
           Vital capacity0.330.07
           FEV1/FVC−0.150.42
           DLCO0.050.78
          At peak exercise
           mPAP0.70<0.01
           Cardiac index−0.60<0.01
           TPR0.80<0.01
           SpO2−0.190.29
           SvO2−0.150.40

          TPR: total pulmonary resistance; SpO2: peripheral arterial oxygen saturation; SvO2: mixed venous oxygen saturation; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide.

          Supplementary Materials

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            Supplementary material 00725-2020.supplement

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          Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy
          Mari Nishizaki, Aiko Ogawa, Hiromi Matsubara
          ERJ Open Research Jan 2021, 7 (1) 00725-2020; DOI: 10.1183/23120541.00725-2020

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          Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy
          Mari Nishizaki, Aiko Ogawa, Hiromi Matsubara
          ERJ Open Research Jan 2021, 7 (1) 00725-2020; DOI: 10.1183/23120541.00725-2020
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