Guide to the interpretation of Cardiopulmonary Exercise Testing

Transcription

1 Guide to the interpretation of Cardiopulmonary Exercise Testing Dr. Ines Frederix December 2014

2 Copyright: Ines Frederix

3 1 Ergospirometry: parameter description Cardiovascular parameters Heart rate (HR) Blood pressure (BP) Oxygen consumption (VO2) Oxygen pulse (π O2) Metabolic parameters Respiratory exchange ratio (RER) (First) Anaerobic threshold (AT1, VT1) (Second) Anaerobic threshold (AT2, VT2, RCP) Ventilatory and pulmonary gas exchange parameters Minute ventilation (VE) Carbon dioxide output (VCO2) Tidal volume (VT) and breathing frequency (fr) VD/VT Oxygen saturation (SaO2) Carbon dioxide respiratory equivalent (VE/VCO2) Oxygen respiratory equivalent (VE/VO2) PET O2 and PET CO VE/VCO2 slope Ventilatory reserve (VR) Typical ergospirometry patterns, associated with specific pathologies/conditions Cardiovascular pathologies Heart failure (HF), diagnostic evaluation Heart Failure (HF), prognostic evaluation Coronary artery disease Respiratory pathologies Chronic Obstructive Pulmonary Disease (COPD) Interstitial Lung Disease (ILD) Pulmonary Vascular Disease (PVD) Neuromuscular pathologies Mitochondrial myopathy Other pathologies/conditions Deconditioning Hyperventilation syndrome/anxiety Obesity Poor effort and malingering Copyright: Ines Frederix

4 2.5 Summary of pathology specific ergosprimetry patterns Algorithm for ergospirometry analysis What is the indication for the ergospirometry? Assess patient s history, clinical examination, other examinations (RxTx, ECG, PFTs, etc.) Was the ergospirometry maximal? Is aerobic capacity (VO2 max) normal? Does cardiovascular function contribute to exercise limitation? Does ventilatory function (respiratory mechanics) contribute to exercise limitation? Does pulmonary gas exchange (hypoxemia, inefficient ventilation, increased dead space ventilation) contribute to exercise limitation? Integrate all results in final conclusion(s) Reference values Graphic representation of cardiopulmonary exercise response in healthy person References Copyright: Ines Frederix

5 1 Ergospirometry: parameter description 1.1 Cardiovascular parameters Heart rate (HR) In healthy subjects, HR increases nearly linearly with increasing VO2; initially due to vagal withdrawal and subsequently due to increased sympathetic activity. Achievement of agepredicted values for maximal HR during exercise is often used as one of the markers to define a maximal ergospirometry test (and hence VO2 max). The most widely used reference value equation for maximal HR is: HR max predicted = 220-age (years). The difference between the age-predicted maximal HR and the maximal HR achieved during ergospirometry is called the Heart Rate Reserve (HRR). Normally HRR < 15 beats/min; in case of a maximal exercise test. When the HRR is zero, there is cardiovascular limitation to exercise (in healthy subjects cardiovascular, rather than ventilatory limitation is mostly observed). When the HR max < 85% HR max predicted; there is chronotropic incompetence. Note: the effect of beta-blockers on HR Blood pressure (BP) Systolic BP typically rises progressively during incremental exercise, diastolic BP remains constant or slightly declines. If systolic BP does not increase with exercise, or in fact declines; the exercise test should be terminated since this could indicate a serious abnormality such as HF, ischemia, aortic stenosis,. Maximal BP s during exercise testing are 220/90 mmhg Oxygen consumption (VO2) VO2 is defined as the volume of O2 extracted from inspired air in a given period of time. It can be expressed by the Fick equation, that is: VO2= Qc x C(a-v)O2. This VO2 max is defined during incremental exercise testing, as the VO2 attained during the VO2 plateau phase; when the VO2 plateaus despite work rate continuing to increase. The VO2 max is the gold standard to define a patient s aerobic capacity. It is influenced by cardiovascular (central), pulmonary (central) and muscular (peripheral) function. To calculate VO2 for a maximal incremental cycle exercise test, we use the following formula: Male: W (predicted weight ie. 0,79xH 60,7) x [50,75-0,372 (A)] Female: (W (predicted weight ie. 0,65xH -42,8) + 43) x [22,78 0,17 (A)] W(eight) in kg, H(eight) in centimeters, A(ge) in years Normal value for VO2 max: VO2 max > 84% predicted (Ref. 1), > 100% predicted (Ref. 2) Oxygen pulse (π O2) The π O2 is defined as: π O2= VO2/HR=SV x C (a-v)o2. The basic profile for the π O2 is to initially increase in a hyperbolically fashion, followed by a slow approach to an asymptotic Ines Frederix 5

6 value. A low, unchanging or flat π O2; with increasing work rate may be interpreted as resulting from a reduced SV. The normal absolute value of π O2 is > 80%. 1.2 Metabolic parameters Respiratory exchange ratio (RER) The RER is defined as : RER= VCO2/VO2. The RER is determined by the fuels used for metabolism. RER is 1 for carbohydrates; RER is 0,7 for lipids and RER is 0,85 for carbohydrates and lipids. A RER > 1,1 is one of the criteria to define a maximal exercise test (First) Anaerobic threshold (AT1, VT1) The AT1 is defined as the moment when there is a transition between no or little lactate accumulation; to a sustained increase in lactate accumulation. It corresponds to the VO2 above which anaerobic energy production substantially supplements aerobic energy production. It is valuable in setting the intensity for exercise prescription in a highly individualized manner. Normally AT1 equals > 40% VO2 max predicted (wide range of normal 40-80%). AT1 can be determined in different ways: 1. V-slope method: AT1 is identified as the VO2 at which the change in slope of the relationship of VO2 to VCO2 occurs. 2. Respiratory equivalent method: AT1 is defined as the VO2 at which there is significant increase in the VO2 respiratory equivalent, without concomitant increase in the VCO2 respiratory equivalent. 3. PET method: AT1 corresponds to the increase in PET O2 (because of hyperventilation) with no simultaneous decrease in PET CO (Second) Anaerobic threshold (AT2, VT2, RCP) AT2 is defined as the VO2 (% VO2 max) at which the carbon dioxide respiratory equivalent starts to increase (after an initial decrease). AT2 marks the onset of hyperventilation ( respiratory compensation ) during incremental exercise. It physiologically reflects the failing of the body s buffering mechanisms; which leads to metabolic (lactic) acidosis. Normally AT2 is 60-90% VO2 max predicted. 1.3 Ventilatory and pulmonary gas exchange parameters Minute ventilation (VE) VE is the volume of expired air exhaled from the lungs in 1 minute. The VE is calculated as: VE = VT x fb. With incremental exercise testing; VE increases progressively. The rise in VE with exercise is primarily associated with an increase in VT during low levels of exercise. As exercise progresses, both VT and fb increase until 70-80% of peak exercise; thereafter fb predominates Carbon dioxide output (VCO2) VCO2 is defined as the amount of CO2 exhaled from the body per unit of time. Ines Frederix 6

7 1.3.3 Tidal volume (VT) and breathing frequency (fb) See I.3.1. Normally the maximal fb is <60 breaths/min VD/VT The VD/VT ratio is an index of gas exchange efficiency. An increase in VD/VT reflects an increased inefficiency of ventilation; due to V/Q mismatching or a right-to-left shunt. Normally VD/VT is 0,30-0,40 in rest. The ratio typically decreases initially with increasing exercise intensity due to increasing VT. Patients with respiratory disease may have at rest either normal or elevated values that fail to decrease normally or may even increase during exercise Oxygen saturation (SaO2) SaO2 is the actual amount of O2 bound to hemoglobin in a given volume of arterial blood Carbon dioxide respiratory equivalent (VE/VCO2) VE/VCO2 corresponds to the number of liters of air that are being breathed to eliminate 1 liter of CO2. Normally minimal VE/VCO2 equals < Oxygen respiratory equivalent (VE/VO2) VE/VO2 corresponds to the number of liters of air that are being breathed for each liter of O2 uptake. Note: The normal pattern of change in VE/VO2 is a drop early in exercise to its nadir near the AT1, and then an increase as maximal exercise capacity is approached. The VE/VCO2 also decreases hyperbolically as work rate increases. For incremental tests, the increase in VE/VO2, that typically occurs in concert with the development of metabolic acidemia (AT1) occurs at a time when VE/VCO2 has not yet increased. It is this profile that separates this response from the onset of hyperventilation from other causes (e.g. anxiety), in which case both VE/O2 and VE/VCO2 would increase in concert. The normal subsequent increase in VE/VCO2 reflects the onset of frank compensatory hyperventilation for metabolic acidosis, with concomitant reduction in PET CO PET O2 and PET CO2 End-tidal PO2 and PCO VE/VCO2 slope During normal incremental exercise testing; VE correlates closely with VCO2 in a linear fashion. The slope of this relationship in normal subjects is (Ref. 1), < 30 (Ref. 2) Ventilatory reserve (VR) The VR is the difference between the ventilatory capacity and the ventilatory demand. The ventilatory capacity is defined by the MVV (Maximal Voluntary Ventilation). MVV is calculated as: MVV= FEV1 x The ventilatory demand is defined by the VE max. To calculate the VR; we use the following formula: VR= VEmax/MVV. Normally during maximal exercise testing; the VE/MVV ratio is 72 ± 15% (Ref. 1), 80% (Ref. 2). Patients with pulmonary disease characteristically have reduced VR; in contrary to healthy people Ines Frederix 7

8 where the exercise test is usually ended by cardiovascular limitation. Thus, VE/MVV has diagnostic utility in determining if unexplained exertional dyspnea is related to a pulmonary mechanism. Ines Frederix 8

9 2 Typical ergospirometry patterns, associated with specific pathologies/conditions 2.1 Cardiovascular pathologies Heart failure (HF), diagnostic evaluation For the cardiovascular parameters: VO2 max: The VO2 max is reduced, reflecting an insufficient increase in cardiac output during exercise. VO2/ W slope: In heart failure this slope is typically decreased due to circulatory insufficiency. πo2: Flattening of the πo2 during incremental exercise, reflects the fall in SV. For the ventilatory parameters: VE/MVV: In general, for patients with heart failure, the cardiopulmonary exercise tests usually are not ventilatory limited. The presence of VE/MVV approaching or exceeding 100% of predicted (reduced VR), signals the presence of combined cardiovascular and respiratory limitation and may suggest concurrent pulmonary disease. VD/VT: The VD/VT is increased due to reduced cardiac output for the metabolic rate; and hence V/Q mismatching. VE/VCO2: The VE/VCO2 is increased due to abnormal V/Q relationships due to low cardiac output for the metabolic rate, subclinical interstitial pulmonary edema,... VE/VCO2 slope > 30 suggests increased filling pressures. Specifically for patients with heart failure with a preserved EF (HFpEF), exercise-induced pulmonary hypertension is characterized by high VE/VCO2 s. For the metabolic parameters AT1: The AT1 is usually decreased; reflecting the circulatory insufficiency and early onset of lactic acid metabolism Heart Failure (HF), prognostic evaluation Prognostic markers in patients with HF VO2 max: The VO2 max is considered one of the most robust prognostic markers in chronic heart failure. A VO2 max of 11 ml/min/kg seems to be the lower threshold for an unfavorable prognosis. VE/VCO2 slope: The VE/VCO2 slope provides additional prognostic information in chronic heart failure patients; The higher the slope, the worse the prognosis. Respiratory oscillations: The presence of respiratory oscillations is a negative prognostic marker. It reflects advanced disease severity and poor prognosis in patients with heart failure. Ines Frederix 9

10 Table 1: Indicates the prognostic and diagnostic stratification for patients with heart failure. Heart Failure VE/VCO2 slope Peak VO2 (ml/kg x min) Respiratory oscillations Blood pressure < 30: Ventilatory Class I >20: Weber Class A Not present Rise in systolic BP during CPET 30-36: Ventilatory Class II 16-20: Weber Class B Not present Flat systolic BP response during CPET 36-45: Ventilatory Class III 10-16: Weber Class C Present Flat systolic BP response during CPET 45: Ventilatory Class IV < 10: Weber Class D Present Drop in systolic BP during CPET Coronary artery disease During exercise testing; the onset of myocardial ischemia impairs ventricular contraction and relaxation functions, thereby reducing the increase in cardiac output during exercise and raising filling pressures. For the cardiovascular parameters: VO2/ W slope: The VO2/ W slope typically starts to flatten and/or decline in case of myocardial ischemia. The normal average slope is 10 ml/min x W. πo2: Flattening of the πo2 during exercise, reflects the inability to adequately increase SV due to myocardial ischemia. Concurrent compensatory more rapid increase in heart rate with respect to work load is often noted. For the ventilatory parameters: VE/VCO2: An increased VE/VCO2 reflects increased filling pressures with exercise. 2.2 Respiratory pathologies Chronic Obstructive Pulmonary Disease (COPD) For the cardiovascular parameters: VO2 max: The VO2 max is reduced in case of severe COPD, and is normal in mild COPD. Ines Frederix 10

11 VO2/ W slope: This slope is usually normal, in contrary to cardiovascular pathologies (HF, coronary artery disease). HRR: There is usually a significant HRR, a reflection that the cardiovascular system has been relatively unstressed. For the ventilatory parameters: VE/MVV: One of the distinguishing features of many patients with moderate to severe COPD is a reduced VR (VE/VMM approaching or exceeding 100%), signaling a significant ventilatory contribution to exercise limitation. VD/VT and VE/VCO2: Both are abnormal reflecting ventilatory inefficiency, due to increased dead space ventilation. PaO2: Patients with COPD usually have low PaO2 values at rest. During exercise PaO2 may increase, decrease or remain the same; but is more likely to be reduced in patients with moderate to severe COPD. For the metabolic parameter: AT1: The AT1 response may be normal, low or indeterminate. A low AT1 may reflect deconditioning due to physical inactivity and/or skeletal muscle dysfunction Interstitial Lung Disease (ILD), Restrictive Lung Disease For the cardiovascular parameters: VO2 max: The VO2 max is typically reduced. HRR: The HRR may be increased or normal, since exercise shows ventilatory limitation. For the ventilatory parameters: VE/MVV: A reduced VR (high VE/MVV) and ventilatory limitation to exercise are often seen; primarily reflecting deranged pulmonary mechanics. VD/VT and VE/VCO2: Inefficient ventilation (increased VE/VCO2 responses) due primarily to increased VD/VT and also hyperventilation due to hypoxemia and mechanoreceptor stimulation are usually observed throughout exercise. PaO2: During exercise, in most patients with significant ILD, impressive arterial desaturation and abnormal increases in P(A-a)O2 are observed. For the metabolic parameter: AT1: The AT1 response can be normal, although a low AT1 commonly occurs and may be due to pulmonary circulatory and/or RV dysfunction (O2 delivery) and/or skeletal muscle dysfunction and deconditioning (O2 utilization) Pulmonary Vascular Disease (PVD) For the cardiovascular parameters: VO2 max: The O2 max is usually reduced. These patients their exercise tests are usually cardiovascular limited. Ines Frederix 11

12 πo2: The πo2 is often reduced, reflecting the heart s inability to maintain adequate cardiac output (CO=SV x HR), in the face of increased pulmonary vascular resistance and consequent RV afterload. For the ventilatory parameters: VE/MVV: As stated above, in PVD patients the exercise test is usually cardiovascular limited. Hence, there is usually VR at peak exercise. VD/VT: The VD/VT is usually increased. VE/VCO2: The VE/VCO2 is typically increased, reflecting inefficient ventilation. For the metabolic parameter: AT1: There is usually an early-onset metabolic acidosis (analogous to heart failure and circulatory insufficiency). Table 2: depicts the diagnostic and prognostic stratification of patients with PVD. Pulmonary Vascular Disease VE/VCO2 slope Peak VO2 (ml/kg x min) PET CO2 apex during exercise Blood pressure SaO2 < 30: Ventilatory Class I >20: Weber Class A > 37 mmhg Rise in systolic BP during CPET No SaO : Ventilatory Class II 16-20: Weber Class B mmhg Flat systolic BP response during CPET > 5% from baseline 36-45: Ventilatory Class III 10-16: Weber Class C mmhg Flat systolic BP response during CPET > 5% from baseline 45: Ventilatory Class IV < 10: Weber Class D < 20 mmhg Drop in systolic BP during CPET > 5% from baseline (PET CO2 apex achieved at submaximal levels, typically immediately proceeds ventilatory threshold) Ines Frederix 12

13 2.3 Neuromuscular pathologies Mitochondrial myopathy In mitochondrial myopathy, a number of genetic mutations can lead to inefficient oxygen utilization by muscle tissue. If mitochondrial myopathy is suspected, a muscle biopsy would be warranted to confirm the diagnosis. For the cardiovascular parameters: VO2 max: The degree of impairment in VO2 max appears to correlate to the severity of genetic mutation. VO2/ W slope: This slope is typically reduced, reflecting the inefficient use of oxygen by the muscle tissue. Q/ VO2: In normal circumstances, where oxygen utilization and delivery are well matched, the Q/ VO2 slope is 5 L/min. In subjects with mitochondrial myopathies, this slope is much higher ( 7) as oxygen delivery far exceeds the capacity for utilization. For the ventilatory parameters: VE/VO2: The VE/VO2 at peak exercise is typically increased, as the ventilatory cost of VO2 dramatically rises due to aerobic inefficiency by affected skeletal muscle. For the metabolic parameter: RER: High RER s during cardiopulmonary exercise testing are seen in case of mitochondrial myopathy. 2.4 Other pathologies/conditions Deconditioning For the cardiovascular parameters: VO2 max: The VO2 max is usually normal. However it can be low or at the lower limit of normal in subjects who are very deconditioned. πo2: πo2 is typically decreased. For the ventilatory parameters: VE/MVV: There is usually a significant ventilatory reserve. VD/VT and VE/VCO2: The ventilatory response to low levels of exercise is usually normal. However, increased submaximal VE is observed at any level of VO2 above the AT1 as a reflection of increased metabolic acidosis, compared with normal subjects. VD/VT responses are normal, as is the VE/VCO2 slope. For the metabolic parameter: AT1: Typically there is early onset of AT1, due to rapid activation of anaerobic metabolism Hyperventilation syndrome/anxiety For the cardiovascular parameters: Ines Frederix 13

14 VO2 max: These patients have a normal VO2 max. For the ventilatory parameters: VE/VCO2: The basic mechanism is increased ventilation as evidenced by abnormal increases in VE, VE/VCO2, respiratory frequency and respiratory alkalosis (evidenced by decreased PET CO2 and PaCO2). As an increased VE/VCO2 may reflect inappropriate ventilation and/or dead space ventilation; arterial PCO2 sampling is recommended. In contrast to the usual gradual increase in respiratory frequency seen during progressive exercise, subjects with psychogenic disorders may have an abrupt turned on onset of regular, rapid and shallow breathing disproportionate to the metabolic stress. Also, at the start of exercise testing, these patients often show an increased breathing frequency (> 20 breaths/min), when compared to normal patients (±10 breaths/min) Obesity For the cardiovascular parameters: VO2 max: VO2 max may be decreased when expressed per kilogram of actual body weight; or normal when expressed per kilogram of ideal body weight. πo2: The πo2 is usually normal. VO2/W slope: in severe obesity, the VO2/W slope is typically increased due to increased oxygen consumption for a given work load, reflecting the increased metabolic need to move the bulky legs. For the ventilatory parameters: VE/MVV: VE/MVV is usually normal, but may be increased in extreme obesity. VD/VT and VE/VCO2: These parameters are usually normal in obesity. Note: in severe obesity, initial pulmonary function tests can show a restrictive pattern. During exercise testing relatively small tidal volumes (reflecting rapid and superficial breathing) can be noted. For the metabolic parameter: AT1: The AT1 is usually normal Poor effort and malingering This should be suspected in case of early cessation of exercise and a reduced VO2 peak; a normal or unattained AT1, a low RER value at exercise cessation and a substantial HRR and VR with no readily apparent peripheral abnormality. Ines Frederix 14

15 2.5 Summary of pathology specific ergosprimetry patterns Table 3: summarizes the most important ergospirometric findings for each of the pathologies discussed in chapter II Typical ergospirometry patterns, associated with specific pathologies/conditions. NA: Not available. Cardiovascular Ventilatory Metabolic VO2 max or VO2 peak Peak HR πo2 Pathology Cardiovascular Heart Failure Decreased Variable Decreased Normal or Coronary artery disease (VE/MVV) x100= VR VD/VT decreased Decreased NA Decreased NA NA Normal/increas ed Respiratory COPD Decreased Decreased, normal in mild VE/VCO2 (at AT1) PaO2 AT1 Increased Increased Normal Decreased Normal Normal/decreased Normal (or decreased) Increased Increased Increased Variable Normal (decreased/intermediat e) Increased Increased Decreased Normal (or decreased) ILD Decreased Decreased Normal (or decreased) Normal or increased PVD Decreased Normal or slightly (Normal) or Normal Increased Increased Decreased Decreased decreased decreased Neuromuscular Other Deconditioning Decreased Normal or slightly Decreased Normal Normal Normal Normal Normal or decreased decreased HV Normal Normal Normal NA NA Increased Normal Normal Obesity Decreased for actual (normal for ideal weight) Normal or slightly decreased Normal Normal (or increased) Normal Normal Normal Normal (or decreased) Ines Frederix 15

16 3 Algorithm for ergospirometry analysis 3.1 What is the indication for the ergospirometry? Before starting the interpretation of the cardiopulmonary exercise test; it is of primordial importance to know the exact indication for the test. The main indications for cardiopulmonary exercise testing are the following: 1. Evaluation of exercise intolerance - Determination of functional impairment or capacity (VO2 peak) - Determination of exercise-limiting factors and pathophysiologic mechanisms 2. Evaluation of patients with cardiovascular disease - Functional evaluation and prognosis in patients with heart failure - Selection for cardiac transplantation - Exercise prescription and monitoring response to exercise training for cardiac rehabilitation 3. Evaluation of patients with respiratory disease 4. Specific clinical applications 3.2 Assess patient s history, clinical examination, other examinations (RxTx, ECG, PFTs, etc.) 3.3 Was the ergospirometry maximal? Patient effort during cardiovascular exercise testing can be considered to be maximal if one or more of the following occur: 1. The patient achieves predicted peak VO2 and/or a plateau on the VO2 curve is observed 2. The predicted maximal work rate is achieved 3. The achieved HR is > 85% HR max predicted (cardiovascular limitation) 4. The VE max approaches or exceeds MVV (ventilatory limitation) 5. RER achieved is > 1,1 6. Patient exhaustion/borg scale rating of 9-10 on a 0-10 scale 3.4 Is aerobic capacity (VO2 max) normal? Normally, the observed VO2max > 84% VO2 max predicted (Ref. 1), >100% VO2 max predicted (Ref. 2). The distinction between (ab)normal VO2 max guides the clinician in a first direction regarding possible underlying pathology (ies). 3.5 Does cardiovascular function contribute to exercise limitation? The cardiopulmonary exercise test is considered cardiovascular limited in case of reduced HRR with normal or increased VR. In healthy people, cardiopulmonary exercise test are usually cardiovascular limited. 3.6 Does ventilatory function (respiratory mechanics) contribute to exercise limitation? Ines Frederix 16

17 The cardiopulmonary exercise test is considered ventilatory limited, in case the VE max approaches or exceeds VMM in the presence of increased HRR. 3.7 Does pulmonary gas exchange (hypoxemia, inefficient ventilation, increased dead space ventilation) contribute to exercise limitation? Exercise hypoxemia most often reflects intrinsic pulmonary gas exchange limitation. A fall in SaO2 ( SaO2) of 4%, SaO2 88%, or PaO2 55 mmhg during cardiopulmonary exercise testing is usually considered clinically significant. 3.8 Integrate all results in final conclusion(s) The observed ergospirometric patterns can help guide the clinician in his diagnostic/therapeutic thinking. However, frequently different pathophysiologic mechanisms contribute concomitantly to the patient s symptoms/exercise intolerance. Therefore, an integrative approach considering all ergospirometric parameters and also the patient s history, clinical examination and static examinations is highly encouraged. Figure 1: depicts the basic strategy for the interpretation of peak cardiopulmonary exercise test results. Ines Frederix 17

18 Ines Frederix 18

19 4 Reference values Table 4: depicts the formula and reference values for the most important cardiovascular, ventilatory and metabolic parameters; given a maximal cardiopulmonary exercise test (as defined in section 3.3). Parameter Formula (max ErgoSx) Reference values Cardiovascular Heart rate HR max= 220 -age > 85% age predicted HRR HRR= HR pred - HR max < 15 beats/min VO2 max VO2 max= Qc x c(a-v)max > 84% (Ref. 1), > 100% (Ref. 2) predicted πo2 πo2= SV x C(a-v)O2 > 80% VO2/ W / Normal average slope is 10 Ventilatory VE VE= VT x fb / fb fb= VE/VT < 60 breaths/min VD/VT / < 0,28 for age < 40 years; < 0,30 for age > 40 years VE/VCO2 slope VE/ VCO (Ref 1.), < 30 (Ref. 2) VE/VCO2 (at AT1) / < 34 SaO2 / < 4% (Ref. 1), < 5% (Ref. 2) Minimal SaO2 / Should be 95% throughout exercise VR VR= VEmax/VMM 72 ± 15% (Ref. 1), 80% (Ref. 2) Metabolic RER RER= VCO2/VO2 > 1,1 AT1 / 40-80% VO2 max predicted (Ref. 1); 40-60% VO2 max predicted (Ref. 2) AT2 (RCP) / % VO2 max predicted (Ref. 2) Ines Frederix 19

20 5 Graphic representation of cardiopulmonary exercise response in healthy person Figure 2: depicts a graphic representation of the maximal, incremental cardiopulmonary exercise response of a healthy aged person. Ines Frederix 20

21 6 References ATS/ACCP Statement on Cardiopulmonary Exercise Testing. Am J Respir Crit Care Med 2003; 167: Milani R, Lavie C, Mehra M, et al. Understanding the Basics of Cardiopulmonary Exercise Testing. Mayo Clin Proc. 2006; 81: Mezzani A, Agostoni P, Cogen-Solal A, et al. Standards for the use of cardiopulmonary exercise testing for the functional evaluation of cardiac patients: a report from the Exercise Physiology Section of the European Association for Cardiovascular Prevention and Rehabilitation. Eur J cardiovasc prev rehabil 2009; 16: Guazzi M, Adams V, Conraads V, et al. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Eur Heart J 2012; Dubowy K, Baden W, Bernitzki S, et al. A practical and transferable new protocol for treadmill testing of children and adults. Cardiol Young 2008; 18: Gläser S, Friedrich N, Koch B, et al. Exercise Blood Pressure and Heart Rate Reference Values. Heart, Lung and Circulation 2013; 22: Paap D, Takken T. Reference values for cardiopulmonary exercise testing in heathy adults: a systematic review. Expert Rev. Cardiovasc. Ther. 2014; 12: Koch B, Schäper C, Itterman T, et al. Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study. Eur Respir J 2009; 33: Cohen-Solal A, Carré F. Practical Guide to Cardiopulmonary Exercise Testing. Elsevier Masson pp Ines Frederix 21