Table 1.
Cardiopulmonary exercise testing variables delineating oxygen pathway defects, and risk stratification in heart failure with preserved ejection fraction
| Variable | Cut‐off | Interpretation |
|---|---|---|
| Quantification of exercise intolerance | ||
| RER | <1.0 ≥ 1.0, preferably ≥1.1 | Definition of submaximal or maximal exercise testing 73 , 112 |
| Peak VO2 (ml/kg/min) | Weber class A >20.0, B 16.0–20.0, C 10.0–15.9 D <10.0 or age‐ and sex‐specific cut‐offs | Categorization of cardiorespiratory fitness can be used in maximal exercise tests either classified based on Weber or on healthy adult cohorts 73 , 113 |
| OUES (L/min/log[L/min]) | Age‐ and sex‐specific cut‐offs | Submaximal parameter that correlates with peak VO2 113 , 114 |
| VO2@VT1 (ml/kg/min) | Age and sex‐specific cut‐offs | Submaximal parameter that correlates with peak VO2 113 |
| Ventilatory mechanical limitation | ||
| BR (%) | <15–20 | Ventilatory limitation 77 |
| VFL/VT (%) | >50 | Expiratory airflow limitation 77 |
| IC (ml) | Decrease >140 | Dynamic hyperinflation 77 |
| EELV (ml) | Increase instead of decrease | Dynamic hyperinflation 77 |
| Pulmonary vascular limitations defined by gas exchange abnormalities and/or haemodynamics | ||
| VE/VCO2 slope (L/min/ml/kg/min) | >30 | Reduced ventilatory efficiency due to increased ventilation and/or increased death space ventilation. 112 Elevations associated with higher PVR and more severe diseases in HFpEF patients with PH 115 |
| VE intercept | <2.64 L/min | May discriminate HFpEF from COPD HFpEF 116 |
| SaO2 (%) | Decrease ≥5 | Gas exchange abnormalities, most commonly related to V/Q mismatch 73 , 77 |
| VD/VT (%) a | No decrease from baseline or blunted response | Increased dead space ventilation related to V/Q mismatch and/or rapid shallow breathing, 77 associated with increased PVR and PH in HFpEF 115 |
| PA–aO2 a (mmHg) | Increase above age‐ and sex‐specific normal values | Gas exchange abnormalities, most commonly related to V/Q mismatch 77 , 117 |
| PaO2 (mmHg) a | Decrease ≥10 | Gas exchange abnormalities, most commonly related to V/Q mismatch 77 |
| Exercise PCWP (mmHg) b | ≥25 | Cut‐off for exercise‐induced PH with limited validity 76 , 93 |
| ΔPAP/ΔCO (mmHg/L/min) b | >3 | Alternative marker of exercise‐induced PH 76 , 93 |
| ΔTPG/ΔCO (mmHg/L/min) b | >1 | Pre‐capillary PH 76 , 93 |
| Cardiovascular limitations defined by gas exchange abnormalities and/or haemodynamics | ||
| VO2/work rate trajectory (ml/kg/min/W) | Flattening or decline | LV dysfunction due to myocardial ischaemia, 118 or right‐sided cardiac dysfunction and PH in HF 85 |
| O2 pulse trajectory (ml/kg/min/bpm) | Flattening or decline | LV dysfunction due to myocardial ischaemia 118 |
| HR/VO2 slope (bpm/ml/kg/min) | >50 | Relative tachycardia to VO2 77 |
| MCR | ≤0.80 or <0.62 on beta‐blocker | Chronotropic incompetence 40 |
| ΔPCWP/ΔCO slope (mmHg/L/min) b | >2 | Impaired LV reserve capacity 76 , 111 |
| Exercise RAP (mmHg) b | >PCWP | RV dysfunction 76 |
| ΔCO/ΔVO2 slope (ml blood/ml O2) b | <4.8 | Impaired CO reserve due to cardiac limitations or preload reserve failure 14 |
| Peripheral muscle limitations | ||
| VO2@VT1 (ml/kg/min) | <40% of predicted | Early first ventilatory threshold suggests peripheral muscle limitation 77 |
| Peak C(a–v)O2 (ml/dl) b | <0.8*haemoglobin | Impaired peripheral O2 utilization 76 |
| VO2 kinetics | MRT <60 s | Impaired peripheral O2 utilization in HFpEF, 119 may also indicate impaired RV pulmonary vascular function in HFrEF 120 |
| Risk stratification | ||
| VO2peak (ml/kg/min) | <14 | Predicts higher risk of HF hospitalization and the composite outcome of all‐cause death, LVAD implantation, or heart transplantation, in particular when combined with VE/VCO2 slope >30 108 |
| VE/VCO2 slope | >30 |
Predicts higher risk of HF hospitalization and the composite outcome of all‐cause death, LVAD implantation, or heart transplantation, in particular when combined with VO2peak <14 ml/kg/min 108 Predicts mortality in HFpEF patients with PH 81 |
| EOV | Present | Predicts higher risk of CV death 87 |
| HRR at 1 min (bpm) | <12 decrease | Predicts higher risk of CV death 121 |
| PCWP/CO slope (mmHg/L/min) b | >2 | Predicts higher risk of the composite outcome of CV death, HF hospitalization, or abnormal resting PCWP on future right heart catheterization 111 |
| PCWP/workload/kg (mmHg/W/kg) b | >25.5 | Predicts higher risk of all‐cause mortality, independently of baseline PCWP 105 |
| PAP/CO slope (mmHg/L/min) b | >3 | Predicts higher risk of first HF hospitalization or all‐cause mortality, both in patients with or without resting PH 96 , 102 |
BR, breathing reserve; C(a–v)O2, difference in oxygen content in arterial and mixed venous blood; CO, cardiac output; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; EELV, end‐expiratory lung volume; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; HRR, heart rate reserve; IC, inspiratory capacity; LV, left ventricular; LVAD, left ventricular assist device; MCR, metabolic–chronotropic relationship; OUES, oxygen uptake efficiency slope; PA‐aO2, alveolar–arterial oxygen gradient; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RAP, right atrial pressure; RER, respiratory exchange ratio; SaO2, arterial oxygen saturation; TPG, transpulmonary gradient; VCO2, carbon dioxide output; VD/VT, ratio of dead‐space ventilation to tidal ventilation; VFL/VT, percent of the tidal breath that expiratory airflow exceeds the maximal flow/volume envelope; VE, minute ventilation; VE/VCO2, minute ventilation to carbon dioxide output; VO2, oxygen uptake; VT, ventilatory threshold (VT1/VT2 corresponding to anaerobic threshold/respiratory compensation point).
Derived from additional arterial blood gas analysis.
Derived from additional invasive measurement (right heart catheterization).