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Cardiopulmonary Exercise Testing






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Cardiopulmonary Exercise Testing

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1. Cardiopulmonary Exercise Testing Antara Mallampalli, M.D.

4. What is Cardiopulmonary Exercise Testing (CPET)? Measurement of rate of oxygen uptake (VO2), rate of CO2 production (VCO2), minute ventilation and other ventilatory parameters while monitoring 12-lead ECG, BP and O2 saturation during maximal ?symptom-limited? exercise

5. During exercise, patient breathes into a mouthpiece connected to computerized system which provides breath-by-breath analysis of expired gases, including air flows, O2 fraction, and CO2 concentration. During exercise, patient breathes into a mouthpiece connected to computerized system which provides breath-by-breath analysis of expired gases, including air flows, O2 fraction, and CO2 concentration.

6. Types of Exercise Used for CPET Usually use either bicycle ergometer or treadmill VO2max with bicycle ergometry usually 5-11% less than with treadmill (no arm movement, no weight-bearing) must compare with appropriate normals Usual protocols: incremental or ramp increase work rate by 5-25 W/min aim to achieve max exercise in 8-12 minutes Advantages of bike: no balance problems, allows accurate measurements of external work output (watts, resistance) not available on the treadmill, cheaper/less space needed, easier to measure BP and ABGs. Advantages of treadmill: more natural exercise, often more comfortable for patients. Start by estimating clinically the patient's exercise capacity -- if low use lower increments. Begin with 2 min at rest with mouthpiece and then 2 min free wheeling or walking at lowest speed, then increase the power output by appropriate increments until exhaustion. Advantages of bike: no balance problems, allows accurate measurements of external work output (watts, resistance) not available on the treadmill, cheaper/less space needed, easier to measure BP and ABGs. Advantages of treadmill: more natural exercise, often more comfortable for patients. Start by estimating clinically the patient's exercise capacity -- if low use lower increments. Begin with 2 min at rest with mouthpiece and then 2 min free wheeling or walking at lowest speed, then increase the power output by appropriate increments until exhaustion.

7. Indications for CPET Diagnosis unexplained dyspnea exercise limitation documenting exercise-induced hypoxemia, titrating O2 prescription exercise-induced asthma Diagnostic evaluation of otherwise unexplained exertional dyspnea or exercise intolerance. Resting measurements of respiratory or cardiac function cannot accurately predict exercise performance. Clinical applications ? specific indications Assessment of functional capacity: disability evaluation, preoperative evaluation, selection for cardiac transplantation, prognostic evaluation Diagnostic: unexplained dyspnea or exercise limitation, picking up early (occult) disease, documenting exercise-induced hypoxemia Assessment of response to treatment Exercise prescription: pulmonary or cardiac rehabilitation, athletic training. Diagnostic evaluation of otherwise unexplained exertional dyspnea or exercise intolerance. Resting measurements of respiratory or cardiac function cannot accurately predict exercise performance. Clinical applications ? specific indications Assessment of functional capacity: disability evaluation, preoperative evaluation, selection for cardiac transplantation, prognostic evaluation Diagnostic: unexplained dyspnea or exercise limitation, picking up early (occult) disease, documenting exercise-induced hypoxemia Assessment of response to treatment Exercise prescription: pulmonary or cardiac rehabilitation, athletic training.

8. Indications for CPET (cont?d) Assessment of functional exercise capacity impairment or disability evaluation preoperative evaluation selection of patients for cardiac transplantation prognosis: CF, heart or pulmonary vascular disease May be helpful when patients? symptoms do not match resting PFTs/echo Preop evaluation for lung cancer resection surgeries ? may have a role in evaluation of borderline patients. Prognostic utility esp in CHF and CFMay be helpful when patients? symptoms do not match resting PFTs/echo Preop evaluation for lung cancer resection surgeries ? may have a role in evaluation of borderline patients. Prognostic utility esp in CHF and CF

9. Cardiac Transplant Evaluation A total of 116 patients were divided into three groups based on the results of their cardiopulmonary stress tests. Group 1 was composed of patients with a peak VO2 of less than 14 mL/kg/min who were accepted as transplant candidates (n= 35). Group 2 was patients with a peak VO2 of more than 14 mL/kg/min who had transplant deferred (n= 52). Group 3 included patients with a peak VO2 of less than 14 mL/kg/min but with a significant comorbidity that precluded transplant (n= 27). Age, left ventricular ejection fraction, and resting hemodynamic parameters were similar among the groups. As depicted in Figure 2, the 1-year survival rate was 94% in the patient group with a VO2 of more than 14 mL/kg/min.A total of 116 patients were divided into three groups based on the results of their cardiopulmonary stress tests. Group 1 was composed of patients with a peak VO2 of less than 14 mL/kg/min who were accepted as transplant candidates (n= 35). Group 2 was patients with a peak VO2 of more than 14 mL/kg/min who had transplant deferred (n= 52). Group 3 included patients with a peak VO2 of less than 14 mL/kg/min but with a significant comorbidity that precluded transplant (n= 27). Age, left ventricular ejection fraction, and resting hemodynamic parameters were similar among the groups. As depicted in Figure 2, the 1-year survival rate was 94% in the patient group with a VO2 of more than 14 mL/kg/min.

11. Preoperative Evaluation for Lung Cancer Resection Routine spirometry and DLCO most useful in evaluating physiologic operability in low-risk patients In high-risk/borderline patients, CPET may have a role along with split-lung function studies Peak VO2 < 50-60% predicted was associated with higher morbidity and mortality after lung resection surgery (Bollinger et al, AJRCCM 1995; Morice et al, Chest 1996)

12. Indications for CPET (cont?d) Exercise prescription: pulmonary or cardiac rehabilitation health maintenance or athletic training Assessing response to therapies More clinically meaningful endpoint than resting PFTs in evaluation of new therapiesMore clinically meaningful endpoint than resting PFTs in evaluation of new therapies

13. Contraindications to CPET acute ischemic changes on ECG unstable angina uncontrolled CHF uncontrolled dysrhythmia third-degree AV block uncontrolled hypertension (SBP>250, DBP>120) thrombophlebitis or intracardiac thrombi acute myocarditis or pericarditis severe AS acute febrile illness O2 saturation < 85% on RA

15. Normal Cardiopulmonary Response to Exercise With maximal exercise, O2 consumption can increase up to 18 times, HR 2 to 3-fold, SV by 2x, CO by 5x, minute ventilation 20-25x, and muscle O2 utilization 2-3x. VO2, VCO2, Ve, and HR increase linearly with increasing external work rate (expressed in watts), with metabolic work accomplished by aerobic mechanisms, until at some point increasing proportions of work are done by anaerobic mechanisms and an ?anaerobic threshold? is said to be reached. After this point, VCO2 and Ve increase disproportionately to VO2. With maximal exercise, O2 consumption can increase up to 18 times, HR 2 to 3-fold, SV by 2x, CO by 5x, minute ventilation 20-25x, and muscle O2 utilization 2-3x. VO2, VCO2, Ve, and HR increase linearly with increasing external work rate (expressed in watts), with metabolic work accomplished by aerobic mechanisms, until at some point increasing proportions of work are done by anaerobic mechanisms and an ?anaerobic threshold? is said to be reached. After this point, VCO2 and Ve increase disproportionately to VO2.

16. Mechanisms of Exercise Limitation ?Reserve?: difference between predicted maximal values and measured values for a given variable Heart rate reserve (HRR) = predicted maximal HR - measured maximal HR Normal: <15 bpm Ventilatory reserve (VR) = MVV ? VEmax, or VEmax/MVV Normal: >11L, or <75-85%

17. Determinants of Peak VO2: the Fick Equation Summarizes the determinants of O2 delivery at rest and with exercise Normally CO increases linearly with workload or VO2. This is accomplished initially by increases in stroke volume primarily, later mainly by increases in HR. Summarizes the determinants of O2 delivery at rest and with exercise Normally CO increases linearly with workload or VO2. This is accomplished initially by increases in stroke volume primarily, later mainly by increases in HR.

18. Heart Rate Predicted HRmax = 220-age Abnormal HR response may reflect disease of either the left or right heart Affected by other factors, including drugs, anxiety, anemia Resting HR: high -- suggests anxiety or disease, low -- suggests good conditioning or conduction problems HR a good noninvasive monitor of cardiovascular response to exercise Maximum HR a good indicator of maximal exercise effort; predicted HRmax usually achieved by normal and unfit persons but not always with severe cardiopulmonary disease ? may develop chronotropic incompetence in late disease. HR Slope = HR/VO2; good indicator of stroke volume over the linear portion of the curve, i.e., between 40-80% VO2max (SV fairly fixed over this range); normal 3.5-4 beats/ml/kg/min O2 pulse reflects capacity of the heart to deliver oxygen per heartbeat. HR a good noninvasive monitor of cardiovascular response to exercise Maximum HR a good indicator of maximal exercise effort; predicted HRmax usually achieved by normal and unfit persons but not always with severe cardiopulmonary disease ? may develop chronotropic incompetence in late disease. HR Slope = HR/VO2; good indicator of stroke volume over the linear portion of the curve, i.e., between 40-80% VO2max (SV fairly fixed over this range); normal 3.5-4 beats/ml/kg/min O2 pulse reflects capacity of the heart to deliver oxygen per heartbeat.

19. O2 Pulse O2 pulse = VO2/HR ml O2 consumed per beat taken to reflect stroke volume assuming PaO2 and C(a-v)O2 respond normally O2 pulse < 80% predicted is abnormal cardiovascular disease anemia (low O2 content), arterial hypoxemia, metabolic myopathies, deconditioning (affect a-v O2 difference)

20. Normal: HR increases fairly linearly with VO2 until max HR reached; O2 pulse increases linearly until a plateau occurs Heart disease: HR vs. VO2 curve shifts leftward and up; O2 pulse reaches an early plateau SV limitation requires higher HR for any level of work

21. Anaerobic Threshold Estimation of the onset of metabolic acidosis Occurs at approximately 40-50% VO2max in normal individuals low (early) AT suggests problems in O2 delivery, muscle oxidative capacity, or both More important is whether it occurs, rather than at what %VO2max indicates test is at least close to maximal exercise not under voluntary control, not affected by psychological factors Normally most of the metabolic work of muscles during exercise is done aerobically, but there will be some workload above which a given person exceeds capacity to do work aerobically and further workloads lead to lactic acidosis due to anaerobic metabolism. This threshold is called AT (LT), thought to correspond to the appearance of increased lactate in the blood. Can be used to indicate level of fitness, to monitor the effects of physical training, and to help in diagnosis of exercise limitation. Thought to reflect hypoxia of the exercising muscles. Normally most of the metabolic work of muscles during exercise is done aerobically, but there will be some workload above which a given person exceeds capacity to do work aerobically and further workloads lead to lactic acidosis due to anaerobic metabolism. This threshold is called AT (LT), thought to correspond to the appearance of increased lactate in the blood. Can be used to indicate level of fitness, to monitor the effects of physical training, and to help in diagnosis of exercise limitation. Thought to reflect hypoxia of the exercising muscles.

22. Anaerobic Threshold Direct measurement requires measuring lactate levels in blood requires frequent blood sampling; impractical Noninvasive assessment using gas exchange parameters buffering of lactate by bicarbonate produces disproportionate increase in VCO2 ?V-slope method?

23. Anaerobic Threshold: V-Slope Method VCO2 plotted against VO2 and intersection of the 2 regression lines is taken to be the anaerobic threshold.VCO2 plotted against VO2 and intersection of the 2 regression lines is taken to be the anaerobic threshold.

24. Blood Pressure Normal resting BP usually < 140/90 At maximum exercise, SBP can increase to about 200 and diastolic to within 10 of resting (i.e., pulse pressure normally increases) Higher values suggest hypertension or CV disease Sometimes difficult to measure with exercise due to motion artifact

25. ECG CPET is also a stress test; done using a 12-lead ECG Observe for conduction problems, arrhythmias, ischemia. Occasional PVCs and nonspecific ST-T changes not uncommon and usually of little clinical significance

26. Ventilatory Response to Exercise Normal resting VE: 5-10 L/min higher suggests anxiety, low suggests either equipment problems or is of no significance Normally, there is adequate ventilatory reserve during exercise MVV = predicted maximum VE peak VE close to or above predicted max VE indicates a ventilatory limitation early in exercise, increase in VE due to increase in VT; later mainly from increase in RR Once Vt reaches 50-60% of VC it starts to plateau; further increases in Ve are due to increases in RR. total Ve = effective or alveolar ventilation + dead space ventilation normally, below the anaerobic threshold, Ve increases linearly with VO2 finding a ventilatory limitation is always abnormal Ventilatory slope = Ve/VO2, measured between 25-50% of VO2max (before - variable, after- increases disproportionately past AT); normal = 25-30 high implies wasted ventilation or anxiety -- use Vd/Vt to help differentiateOnce Vt reaches 50-60% of VC it starts to plateau; further increases in Ve are due to increases in RR. total Ve = effective or alveolar ventilation + dead space ventilation normally, below the anaerobic threshold, Ve increases linearly with VO2 finding a ventilatory limitation is always abnormal Ventilatory slope = Ve/VO2, measured between 25-50% of VO2max (before - variable, after- increases disproportionately past AT); normal = 25-30 high implies wasted ventilation or anxiety -- use Vd/Vt to help differentiate

27. Ventilatory Response to Exercise Normal subjects reach only about 75% MVV with predicted VO2max Lung disease: curve shifts up and left, and MVV is reduced

28. Assessing Gas Exchange SpO2 and blood gases oxygen desaturation implies wasted pulmonary circulation or reduced pulmonary vascular bed P(A-a)O2: normally increases with exercise PaCO2 (or PetCO2) should be close to 40 mmHg before AT low values indicate hyperventilation, high values -- alveolar hypoventilation Oxygen saturation easily monitored noninvasively by pulse oximetry O2 sat: need to see change >4% to consider significant Oxygen saturation easily monitored noninvasively by pulse oximetry O2 sat: need to see change >4% to consider significant

29. Assessing Gas Exchange: Physiologic Dead Space VD/VT = (PaCO2 ? PeCO2)/PaCO2 VD/VT normally ? 0.3, drops to < 0.2 during exercise tidal volume increases improved V/Q matching PeCO2 = mixed expired CO2, the average CO2 concentration of expired gases Measure of ?efficiency? of lung for CO2 elimination (closer PeCO2 is to PaCO2 the more efficient the system) Improved perfusion of upper lung zones during exercise with increased CO and PAP, leading to reduction in high V/Q areas, or reduced dead space ventilation.PeCO2 = mixed expired CO2, the average CO2 concentration of expired gases Measure of ?efficiency? of lung for CO2 elimination (closer PeCO2 is to PaCO2 the more efficient the system) Improved perfusion of upper lung zones during exercise with increased CO and PAP, leading to reduction in high V/Q areas, or reduced dead space ventilation.

30. Spirometry Always done at baseline; post-test spirometry may help in identifying exercise induced asthma Needed to calculate expected VE max (MVV) (=40xFEV1) Tidal and exercise flow-volume loops may provide more information on maximal ventilatory capacity

31. Normal Exercise Tidal Flow-Volume Loops Compares curves for young and old adults achieving roughly same peak VO2. Normally there is flow and volume reserve at rest and throughout exercise. EELV goes below resting FRC during exercise. With aging, there is some flow limitation ? initially mainly encroach on inspiratory reserve volume with minimal inspiratory reserve as exercise progresses, as well as some expiratory flow reserve. Little reserve to either flow or volume at peak exercise.Compares curves for young and old adults achieving roughly same peak VO2. Normally there is flow and volume reserve at rest and throughout exercise. EELV goes below resting FRC during exercise. With aging, there is some flow limitation ? initially mainly encroach on inspiratory reserve volume with minimal inspiratory reserve as exercise progresses, as well as some expiratory flow reserve. Little reserve to either flow or volume at peak exercise.

32. Exercise Tidal Flow-Volume Loops: COPD With COPD there is dynamic hyperinflation during exercise (air trapping) resulting in EELV higher than resting FRC, with lack of flow and volume reserve ? shown graphically as lack of space between exercise tidal loops and maximal resting loop.With COPD there is dynamic hyperinflation during exercise (air trapping) resulting in EELV higher than resting FRC, with lack of flow and volume reserve ? shown graphically as lack of space between exercise tidal loops and maximal resting loop.

33. Approach to Interpretation of CPET Look at both numerical and graphical data Was this a maximal (or near-max) effort? subjective assessment of technicians reached predicted HRmax or VO2max ventilatory limitation development of significant metabolic acidosis (bicarb drop 5mEq or more, R > 1.15) O2 sat drop > 5%

35. Approach to Interpretation of CPET Is the exercise capacity normal? peak VO2, max work rate Is the cardiovascular response normal? HR vs VO2, O2 pulse, anaerobic threshold, VO2 vs work rate Is the ventilatory response normal? VE/MVV, max RR, PaCO2 Is gas exchange normal? VD/VT, VE/VCO2, PaO2, P(A-a)O2, SpO2

36. ?Normal? Values

37. Patterns of Exercise Limitation Cardiomyopathy low peak VO2, no HRR, low O2 pulse, early AT, preserved ventilatory reserve, gas exchange normal (or mild increase in VD/VT) COPD low peak VO2, high HRR, normal or low O2 pulse, normal or indeterminate AT, low ventilatory reserve, high VD/VT at rest and less than normal drop with exercise, oxygenation may be abnormal Normal limitation to maximal exercise thought to be due to cardiovascular factors With reduced VO2max (i.e. < 80% predicted), limitation may be due to one or more of the above categories. Deconditioning often a component of limitation with other factors, e.g., COPD patients with associated peripheral muscle abnormalities and deconditioning; improves with exercise training -- part of why rehabilitation may help Normal limitation to maximal exercise thought to be due to cardiovascular factors With reduced VO2max (i.e. < 80% predicted), limitation may be due to one or more of the above categories. Deconditioning often a component of limitation with other factors, e.g., COPD patients with associated peripheral muscle abnormalities and deconditioning; improves with exercise training -- part of why rehabilitation may help

38. Patterns of Exercise Limitation Pulmonary vascular disease low peak VO2, no HRR, low O2 pulse, early AT, normal ventilatory reserve, prominent abnormal VD/VT (may be high at rest; little drop or even increase with exercise), abnormal oxygenation Obesity low peak VO2/kg, but normal in L/min or normalized to IBW VO2 vs work rate shifted up and left (higher O2 cost to perform external work) otherwise normal responses If VO2max is reduced and HRR is low but there is ventilatory reserve, a cardiovascular limitation to exercise is suspected If there is no VR and there is HRR, a ventilatory limitation can be suspected. May have both in a given patient. With peripheral limitation to exercise, will have low VO2max with preserved HRR and VR. Examples include severe deconditioning, neuromuscular problems, myopathies. If VO2max is reduced and HRR is low but there is ventilatory reserve, a cardiovascular limitation to exercise is suspected If there is no VR and there is HRR, a ventilatory limitation can be suspected. May have both in a given patient. With peripheral limitation to exercise, will have low VO2max with preserved HRR and VR. Examples include severe deconditioning, neuromuscular problems, myopathies.

39. Patterns of Exercise Limitation Deconditioning low peak VO2, borderline abnormal cardiovascular responses, normal ventilatory and gas exchange parameters improves with conditioning normal echocardiogram Poor effort low peak VO2 with no identifiable physiologic limitation (high HRR, normal/high ventilatory reserve, normal gas exchange parameters)

40. ?Typical? Response Patterns on CPET

41. 32 yo woman referred for CPET due to progressive exertional dyspnea. Non-smoker, no other medical problems. Normal spirometry. Maximal cycle ergometer exercise test is done. HRmax 180 bpm 96%pred VO2peak 1.3 L/min 40%pred AT 1.17 L/min 90%VO2max VEmax 60 L/min 42%pred O2 pulse 7.2 ml/beat 41%pred SpO2 96% at rest, 88% at max exercise VD/VT 0.35 at rest, 0.38 at max exercise These results are most consistent with which of the following: Interstitial lung disease Deconditioning Primary pulmonary hypertension Exercise-induced bronchospasm Poor effort/malingering

42. 32 yo woman referred for CPET due to progressive exertional dyspnea. Non-smoker, no other medical problems. Normal spirometry. Maximal cycle ergometer exercise test is done. HRmax 180 bpm 96%pred VO2peak 1.3 L/min 40%pred AT 1.17 L/min 90%VO2max VEmax 60 L/min 42%pred O2 pulse 7.2 ml/beat 41%pred SpO2 96% at rest, 88% at max exercise VD/VT 0.35 at rest, 0.38 at max exercise These results are most consistent with which of the following: Interstitial lung disease Deconditioning Primary pulmonary hypertension Exercise-induced bronchospasm Poor effort/malingering

43. 68 yo woman with 42 pack year smoking history, undergoes CPET for evaluation of worsening exertional dyspnea without cough or sputum production. Had an MI 3 years ago. Exam shows only minimally decreased breath sounds. PFTs show moderate obstruction, FEV1 1.1L (58%pred). CPET results: VO2peak 0.7 L/min 65% pred HRmax 118 bpm 77% pred HRR 34 bpm O2 pulse 6 ml/beat 85% pred VEmax 26 L/min 60% pred AT 0.3 L/min 28% pred VO2 ABG at rest 7.41/42/79 ABG at peak exercise 7.31/34/87 Which of the following best explains the results: Ventilatory limitation Cardiac limitation Submaximal test Deconditioning Peripheral vascular disease

44. 68 yo woman with 42 pack year smoking history, undergoes CPET for evaluation of worsening exertional dyspnea without cough or sputum production. Had an MI 3 years ago. Exam shows only minimally decreased breath sounds. PFTs show moderate obstruction, FEV1 1.1L (58%pred). CPET results: VO2peak 0.7 L/min 65% pred HRmax 118 bpm 77% pred HRR 34 bpm O2 pulse 6 ml/beat 85% pred VEmax 26 L/min 60% pred AT 0.3 L/min 28% pred VO2 ABG at rest 7.41/42/79 ABG at peak exercise 7.31/34/87 Which of the following best explains the results: Ventilatory limitation Cardiac limitation Submaximal test Deconditioning Peripheral vascular disease Combination of decreased peak VO2, preserved HRR and VR, normal ECG, and early AT with metabolic acidosis are best explained by PVD. Submax effort would fit EXCEPT for the metabolic acidosis and early AT. Deconditioning would cause early reaching of peak HR.Combination of decreased peak VO2, preserved HRR and VR, normal ECG, and early AT with metabolic acidosis are best explained by PVD. Submax effort would fit EXCEPT for the metabolic acidosis and early AT. Deconditioning would cause early reaching of peak HR.

45. Which statement is FALSE concerning VO2max? A. Reduced VO2max may reflect poor effort B. VO2max is usually the same for bicycle ergometry and treadmill C. VO2max is age and gender related D. Reduced VO2max with exercise may be due to reduced O2 delivery

46. Which statement is FALSE concerning VO2max? A. Reduced VO2max may reflect poor effort B. VO2max is usually the same for bicycle ergometry and treadmill C. VO2max is age and gender related D. Reduced VO2max with exercise may be due to reduced O2 delivery


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