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Prediction of maximal oxygen uptake from 6-min walk test in pulmonary hypertension

Paula Appenzeller, Fiorenza Gautschi, Julian Müller, Mona Lichtblau, Stéphanie Saxer, Simon R. Schneider, Esther I. Schwarz, Silvia Ulrich
ERJ Open Research 2022 8: 00664-2021; DOI: 10.1183/23120541.00664-2021
Paula Appenzeller
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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Fiorenza Gautschi
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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Julian Müller
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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Mona Lichtblau
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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  • ORCID record for Mona Lichtblau
Stéphanie Saxer
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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  • ORCID record for Stéphanie Saxer
Simon R. Schneider
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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Esther I. Schwarz
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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Silvia Ulrich
1Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland
2University of Zurich, Zurich, Switzerland
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  • ORCID record for Silvia Ulrich
  • For correspondence: silvia.ulrich@usz.ch
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  • FIGURE 1
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    FIGURE 1

    Patient flow chart. 6MWD: 6-min walk distance; PH: pulmonary hypertension; V′O2max: maximal oxygen uptake.

  • FIGURE 2
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    FIGURE 2

    Correlation between 6-min walk distance (6MWD) and maximal oxygen uptake (VO2max). The three panels show the correlation for all observations, the training dataset and the testing dataset. Correlation coefficients (r) and p-values are given for all three datasets separately.

  • FIGURE 3
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    FIGURE 3

    Comparison of predictive models. The panels show the predicted values for maximal oxygen uptake (VO2max) against 6-min walk distance (6MWD) for each model separately. In each panel, the original data from the testing dataset is depicted for comparison; standard error of the estimate (SEE) for each model is shown below the panel headers. Mean oxygen uptake (V′O2) as determined by the generalised equation by Ross et al. [14] is shown in the corresponding panel.

  • FIGURE 4
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    FIGURE 4

    Bland–Altman graphs for the comparison of maximal oxygen uptake (V′O2max) determined by cardiopulmonary exercise testing versus using a predictive model based on 6-min walk test. The x-axis shows the calculated mean between the observed and the predicted values for V′O2max while the y-axis shows the difference between the two methods. The line corresponds to the mean difference in V′O2max and the two dashed lines show the 95% confidence interval. Each panel shows a different model as indicated by the panel's headers.

Tables

  • Figures
  • TABLE 1

    Characteristics of the training and testing datasets

    Training datasetTesting dataset
    Observations n19482
    Female118 (61)58 (71)
    Diagnosis
     PAH117 (60)50 (61)
     PH due to left heart disease1 (1)
     PH due to lung disease4 (2)1 (1)
     CTEPH64 (33)28 (34)
     Miscellaneous8 (4)3 (4)
    Haemodynamics at baseline
     mPAP, mmHg42±4.139±13.0
     PVR, mmHg12±636±4
     PAWP, mmHg11±411±4
     CI, mL/min/kg2.8±0.82.9±0.7
    Characteristics
     Age, years59±1458±15
     Height, cm169±11169±10
     Weight, cm76±1973±17
     BMI, kg/m227±525±5
     NYHA functional class2.2±0.72.2±0.6
    6-min walk test
     6-min walk distance, m504±85503±90
     At rest
      Systolic BP, mmHg125±18120±14
      Diastolic BP, mmHg79±1278±12
      Heart rate, bpm84±1484±12
      Peripheral oxygen saturation, %96±396±3
     At peak exercise
      Systolic BP, mmHg145±25142±26
      Diastolic BP, mmHg83±1482±13
      Heart rate, bpm121±21121±22
      Heart rate response, bpm37±1937±20
      Peripheral oxygen saturation, %89±9.090±7.8
      BORG CR10, score4.7±24.6±2
    Cardiopulmonary exercise test
     V′O2max, mL/min/kg15.3±3.816.1±3.7
     Maximal workload, Watts93±3396±36

    Data are presented as n (%) or mean±sd, unless otherwise stated. BMI: body mass index; BP: blood pressure; CI: cardiac index; CTEPH: chronic thromboembolic pulmonary hypertension; mPAP: mean pulmonary arterial pressure; NYHA: New York Heart Association; PAH: pulmonary arterial hypertension; PAWP: pulmonary arterial wedge pressure; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; V′O2max: maximal oxygen uptake.

    • TABLE 2

      Coefficients of different linear regression models and application to testing data

      Ross et al. [14] mean (r=0.82)p-valueRoss et al. [14] (r=0.59)p-valueMiyamoto et al. [16] (r=0.68)p-valueZapico et al. [17] (R2=0.48)p-valueNew model (R2=0.48)p-value
      Observations n103810832782194
      Intercept4.9484.6824.213−21.6261.830.248
      6MWD, m0.0230.0250.0260.026<0.0010.031<0.001
      Sex4.1030.002
      Height, cm0.1740.043
      Weight, kg−0.0710.02−0.0230.22
      HRR, bpm−0.0150.047
      Applied to testing dataset      
       SEE, mL/min/kg3.033.224.363.08
       SEE% mean19%20%27%19%
      Ability to classify to low risk (V′O2max >15 mL/min/kg)      
       Sensitivity0.960.960.910.69
       Specificity0.230.230.220.78
       PPV0.630.630.630.82
       NPV0.800.800.640.64

      r from correlation between maxima oxygen uptake (V′O2max) and 6-min walk distance (6MWD); R2 from linear regression of V′O2max against 6MWD. HRR: heart rate response in 6-min walk test (heart rate at maximal exercise – heart rate at rest); NPV: negative predictive value; PPV: positive predictive value; SEE: standard error of the estimate; SEE% mean: SEE as percentage of mean peak oxygen uptake. All coefficients, p-values and R2 for Ross et al. [14], Miyamoto et al. [16] and Zapico et al. [17] are copied from the original publications.

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      Prediction of maximal oxygen uptake from 6-min walk test in pulmonary hypertension
      Paula Appenzeller, Fiorenza Gautschi, Julian Müller, Mona Lichtblau, Stéphanie Saxer, Simon R. Schneider, Esther I. Schwarz, Silvia Ulrich
      ERJ Open Research Apr 2022, 8 (2) 00664-2021; DOI: 10.1183/23120541.00664-2021

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      Prediction of maximal oxygen uptake from 6-min walk test in pulmonary hypertension
      Paula Appenzeller, Fiorenza Gautschi, Julian Müller, Mona Lichtblau, Stéphanie Saxer, Simon R. Schneider, Esther I. Schwarz, Silvia Ulrich
      ERJ Open Research Apr 2022, 8 (2) 00664-2021; DOI: 10.1183/23120541.00664-2021
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