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The role of cardiopulmonary exercise tests in pulmonary arterial hypertension

Stefania Farina, Michele Correale, Noemi Bruno, Stefania Paolillo, Elisabetta Salvioni, Roberto Badagliacca, Piergiuseppe Agostoni on behalf of the “Right and Left Heart Failure Study Group” of the Italian Society of Cardiology
European Respiratory Review 2018 27: 170134; DOI: 10.1183/16000617.0134-2017
Stefania Farina
1Centro Cardiologico Monzino, IRCCS, Milan, Italy
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Michele Correale
2Dept of Cardiology, University of Foggia, Foggia, Italy
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Noemi Bruno
1Centro Cardiologico Monzino, IRCCS, Milan, Italy
3AOR S.Carlo, Dipartimento Cardiovascolare, Potenza, Italy
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Stefania Paolillo
4IRCCS SDN, Istituto di ricerca diagnostica e nucleare, Naples, Italy
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Elisabetta Salvioni
1Centro Cardiologico Monzino, IRCCS, Milan, Italy
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Roberto Badagliacca
5Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, “La Sapienza” University of Rome, Rome, Italy
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Piergiuseppe Agostoni
1Centro Cardiologico Monzino, IRCCS, Milan, Italy
6Dept of Clinical Sciences and Community Health (Cardiovascular Section), University of Milan, Milan, Italy
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  • FIGURE 1
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    FIGURE 1

    The minute ventilation (V′E)/carbon dioxide production (V′CO2) relationship slope in two pulmonary arterial hypertension patients. In (a) the physiological behaviour of ventilation during exercise is preserved in spite of hyperventilation, such that two slopes can be recognised around the respiratory compensation (RC) point (slope 1 (S1)=40.4 and slope 2 (S2)=55.1). In (b) a single slope characterises the V′E/V′CO2 relationship.

  • FIGURE 2
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    FIGURE 2

    The minute ventilation (V′E)/carbon dioxide production (V′CO2) relationship slope in a patient with pulmonary arterial hypertension and preserved physiological behaviour of the V′E/V′CO2 relationship during exercise. In the first part of exercise, the V′E/V′CO2 slope is high and the V′E-axis intercept is close to zero. This means that dead space ventilation progressively increases during exercise. After the end of isocapnic buffering, i.e. at the respiratory compensation (RC) point, the slope becomes steeper and the V′E-axis intercept becomes severely negative showing that dead space ventilation severely increases toward the end of exercise. Reproduced from [32] with permission.

  • FIGURE 3
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    FIGURE 3

    Difference of oxygen uptake efficiency (OUE; oxygen uptake (V′O2)/minute ventilation (V′E)) plateau between a typical pulmonary arterial hypertension (PAH) patient and a “normal” control subject. In normal subjects, OUE typically increases during exercise from rest to plateau and then gradually decreases until the end of exercise. It then further decreases in the immediate recovery period and begins stabilising after about 2 min. In PAH patients, OUE changes in a similar way to control subjects but is always lower than in controls in the transition from rest to the end of exercise. Reproduced from [48] with permission.

Tables

  • Figures
  • TABLE 1

    Cardiopulmonary exercise test (CPET) determinants of prognosis in risk assessment

    CPET parametersLow Risk (<5%)Intermediate risk (5–10%)High risk (>10%)
    Peak V′O2 mL·kg−1·min−1>1511–15<11
    Peak V′O2 % predicted>6565–35<35
    V′E/V′CO2 slope<3636–45>45

    V′O2: oxygen uptake; V′E : minute ventilation; V′CO2: carbon dioxide production; V′E/V′CO2 slope: slope of the relationship between V′E and V′CO2.

    • TABLE 2

      Common cardiopulmonary exercise test findings in patients with pulmonary arterial hypertension

      Reduced parametersIncreased parameters
      Peak V′O2VD/VT during exercise (>30%)
      WRPA–aO2 differences during exercise (up to 45 mmHg or over)
      O2 pulse
      V′O2/WR
      PETCO2 at rest
      PETCO2 at AT
      O2 saturation during exercise (drop >3% without PaCO2 rise)

      V′O2: oxygen uptake; VD: dead space volume; VT: tidal volume; WR: work rate; PA–aO2: alveolar–arterial oxygen tension difference; PETCO2: end-tidal carbon dioxide tension; AT: anaerobic threshold; PaCO2: arterial carbon dioxide tension.

      • TABLE 3

        Resting and exercise values in normal subjects and primary pulmonary hypertension (PPH) patients categorised according to severity of reduction in cardiopulmonary exercise test (CPET) aerobic capacity

        ValuesNormal# (n=20)Mild PPH (n=3)Moderate PPH (n=14)Severe PPH (n=22)Very Severe PPH (n=14)
        Peak V′O2 % predicted range82–13265–7950–6435–49<35
        Peak V′O2 % predicted101±1970±458±442±527±4
        Peak V′O2 mL·min−1·kg−129.5±6.614.5±3.312.5±2.211.2±2.68.1±1.7
        AT % predicted104±1685±775±1057±941±7
        AT mL·min−1·kg−116.3±3.910.4±2.39.7±1.38.7±2.26.8±1.3
        Peak O2 pulse % predicted108±2586±1173±856±1139±5
        Peak HR % predicted96±1383±1280±877±1270±13
        ΔV′O2/ΔWR mL·min−1·W−19.6±0.98.3±0.57.0±1.56.0±1.05.6±1.3
        V′E/V′CO2 at AT % predicted99±12142±22149±21161±25219±76
        V′E/V′CO2 at AT absolute29±443±645±746±862±20
        V′E/V′CO2 slope % predicted88±11164±49148±27141±32215±123
        V′E/V′CO2 slope absolute25±349±1445±940±1060±32
        Peak V′E % MVV70±1563±1954±947±1143±16
        MRT s12±1034±937±1447±1364±15
        mPAP mmHg48±1763±1470±1857±17
        CO L min−15.1±1.14.4±1.43.5±1.03.8±1.2
        PVR mmHg·L−1·min−18±415±818±514±6
        NYHA symptom class2.0±0.42.5±0.52.8±0.63.3±0.4

        V′O2: oxygen uptake; AT: anaerobic threshold; HR: heart rate; WR: work rate; V′E: minute ventilation; V′CO2: carbon dioxide production; MVV: maximum voluntary ventilation; MRT: mean response time of V′O2 during unloaded cycling; mPAP: mean pulmonary arterial pressure; CO: cardiac output; PVR: pulmonary vascular resistance; NYHA: New York Heart Association; V′E/V′CO2 slope: slope of the relationship between V′E and V′CO2; V′E/V′CO2 at AT: ratio of ventilation to carbon dioxide output at AT; ΔV′O2/ΔWR: increase in oxygen uptake per increase in work rate. #: each CPET parameter is significantly different for all PPH patients compared to that of normal control subjects (p<0.001). Data is reproduced from [20] with permission.

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        The role of cardiopulmonary exercise tests in pulmonary arterial hypertension
        Stefania Farina, Michele Correale, Noemi Bruno, Stefania Paolillo, Elisabetta Salvioni, Roberto Badagliacca, Piergiuseppe Agostoni
        European Respiratory Review Jun 2018, 27 (148) 170134; DOI: 10.1183/16000617.0134-2017

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        The role of cardiopulmonary exercise tests in pulmonary arterial hypertension
        Stefania Farina, Michele Correale, Noemi Bruno, Stefania Paolillo, Elisabetta Salvioni, Roberto Badagliacca, Piergiuseppe Agostoni
        European Respiratory Review Jun 2018, 27 (148) 170134; DOI: 10.1183/16000617.0134-2017
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        • Article
          • Abstract
          • Abstract
          • Introduction
          • The CPET in PAH: from experience to guidelines
          • Physiology of exercise in PAH
          • The use of the CPET in the diagnosis of PAH
          • The use of the CPET for prognostication in PAH
          • Conclusions
          • Footnotes
          • References
        • Figures & Data
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        • Pulmonary vascular disease
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