1. MITCHELL HOROWITZ Cardiopulmonary Exercise Testing

2. Outline Description of CPET Who should and who should not get CPET When to terminate CPET Exercise physiology Define terms: respiratory exchange ratio, ventilatory equivalent, heart rate reserve, breathing reserve, oxygen pulse Pattern of CPET results COPD vs CHF

3. Rationale for Exercise Testing Cardiopulmonary measurements obtained at rest may not estimate functional capacity reliably

4. Clinical Exercise Tests 6-min walk test  Submaximal Shuttle walk test  Incremental, maximal, symptom-limited Exercise bronchoprovocation Exertional oximetry Cardiac stress test CPET

5. Karlman Wasserman

6. Coupling of External Ventilation and Cellular Metabolism

7. Adaptations of Wasserman’s Gears

8. General Mechanisms of Exercise Limitation Pulmonary  Ventilatory  Respiratory muscle dysfunction  Impaired gas exchange Cardiovascular  Reduced stroke volume  Abnormal HR response  Circulatory abnormality  Blood abnormality Peripheral  Inactivity  Atrophy  Neuromuscular dysfunction  Reduced oxidative capacity of skeletal muscle  Malnutrition Perceptual Motivational Environmental

9. What is CPET? Symptom-limited exercise test Measure airflow, SpO 2, and expired oxygen and carbon dioxide Allows calculation of peak oxygen consumption, anaerobic threshold

10. Components of Integrated CPET Symptom-limited ECG  HR Measure expired gas  Oxygen consumption  CO 2 production  Minute ventilation SpO 2 or PO 2 Perceptual responses  Breathlessness  Leg discomfort

11. Modified Borg CR-10 Scale

12. Indications for CPET Evaluation of dyspnea  Distinguish cardiac vs pulmonary vs peripheral limitation vs other  Detection of exercise-induced bronchoconstriction  Detection of exertional desaturation Pulmonary rehabilitation  Exercise intensity/prescription  Response to participation Pre-op evaluation and risk stratification Prognostication of life expectancy Disability determination Fitness evaluation Diagnosis Assess response to therapy

13. Mortality in CF Patients Nixon et al; NEJM 327: 1785; 1992. Followed 109 patients with CF for 8 yrs from CPET  Peak VO 2 >81% predicted: 83% survival  Peak VO 2 59-81% predicted: 51% survival  Peak VO 2 <59% predicted: 28% survival

14. Mortality in CHF Patients Mancini et al; Circulation 83: 778; 1991. Peak VO 2 >14 ml/kg/min:  1-yr survival 94%  2-yr survival 84% Peak VO 2 ≤14 ml/kg/min:  1-yr survival 47%  2-yr survival 32%

15. CPET to Predict Risk of Lung Resection in Lung Cancer Lim et al; Thorax 65:iii1, 2010 Alberts et al; Chest 132:1s, 2007 Balady et al; Circulation 122:191, 2010 Peak VO 2 >15 ml/kg/min  No significant increased risk of complications or death Peak VO 2 <15 ml/kg/min  Increased risk of complications and death Peak VO 2 <10 ml/kg/min  40-50% mortality  Consider non-surgical management

16. Absolute Contraindications to CPET Acute MI Unstable angina Unstable arrhythmia Acute endocarditis, myocarditis, pericarditis Syncope Severe, symptomatic AS Uncontrolled CHF Acute PE, DVT Respiratory failure Uncontrolled asthma SpO 2 <88% on RA Acute significant non-cardiopulmonary disorder that may affect or be adversely affected by exercise Significant psychiatric/cognitive impairment limiting cooperation

17. Relative Contraindications to CPET Left main or 3-V CAD Severe arterial HTN (>200/120) Significant pulmonary HTN Tachyarrhythmia, bradyarrhythmia High degree AV block Hypertrophic cardiomyopathy Electrolyte abnormality Moderate stenotic valvular heart disease Advanced or complicated pregnancy Orthopedic impairment

18. Indications for Early Exercise Termination Patient request Ischemic ECG changes 2 mm ST depression Chest pain suggestive of ischemia Significant ectopy 2 nd or 3 rd degree heart block Bp sys >240-250, Bp dias >110-120 Fall in BP sys >20 mmHg SpO 2 <81-85% Dizziness, faintness Onset confusion Onset pallor

19. CPET Measurements Work V O 2 V CO 2 AT HR ECG BP R SpO 2 ABG Lactate CP Dyspnea Leg fatigue

20. Exercise Modality Advantages of cycle ergometer  Cheaper  Safer  Less danger of fall/injury  Can stop anytime  Direct power calculation  Independent of weight  Holding bars has no effect  Little training needed  Easier BP recording, blood draw  Requires less space  Less noise Advantages of treadmill  Attain higher VO 2  More functional

21. Incremental vs Ramp Exercise Test Protocol INCREMENTAL RAMP WORK TIME WORK

22. Physiology and Chemistry Slow vs fast twitch fibers Buffering of lactic acid by bicarbonate CO 2 production from carbonic acid Respiratory exchange ratio Ventilatory equivalent of oxygen Ventilatory equivalent of carbon dioxide Graphical determination of AT Fick Equation Oxygen pulse

23. Properties of Skeletal Muscle Fibers Red = Slow twitch = Type I  Sustained activity  High mitochondrial density  Metabolize glucose aerobically  1 glucose yields 36 ATP  Rapid recovery White = Fast twitch = Type II  Rapid burst exercise  Few mitochondria  Metabolize glucose anaerobically  1 glucose yields 2 ATP and 2 lactic acid  Slow recovery

24. Lactic Acid is Buffered by Bicarbonate Lactic acid + HCO 3 → H 2 CO 3 + Lactate ↓ H 2 O + CO 2

25. Respiratory Exchange Ratio RER= CO 2 produced / O 2 consumed = V CO 2 / V O 2

26. Ventilatory Equivalents Ventilatory equivalent for carbon dioxide = Minute ventilation / V CO 2  Efficiency of ventilation  Liters of ventilation to eliminate 1 L of CO 2 Ventilatory equivalent for oxygen = Minute ventilation / V O 2  Liters of ventilation per L of oxygen uptake

27. Relationship of AT to RER and Ventilatory Equiv for O 2 Below the anaerobic threshold, with carbohydrate metabolism, RER=1 (CO 2 production = O 2 consumption). Above the anaerobic threshold, lactic acid is generated. Lactic acid is buffered by bicarbonate to produce lactate, water, and carbon dioxide. Above the anaerobic threshold, RER >1 (CO 2 production > O 2 consumption). Carbon dioxide regulates ventilation. Ventilation will disproportionately increase at lactate threshold to eliminate excess CO 2. Increase in ventilatory equivalent for oxygen demarcates the anaerobic threshold.

28. Lactate Threshold

29. Determination of AT from RER Plot (V Slope Method)

30. Determination of AT from Ventilatory Equivalent Plot

31. Wasserman 9-Panel Plot

32. Oxygen Consumption: Fick Equation Fick Equation: Q = V O 2 / C(a-v) O 2 V O 2 = Q x C(a-v) O 2 V O 2 = SV x HR x C(a-v) O 2 Heart disease Lung disease Muscle disease Deconditioning Anemia Lung disease (low SaO 2 ) Arterial oxygen content = (1.34)(SaO 2 )(Hgb) Venous oxygen content = (1.34)(SvO 2 )(Hgb)

33. Oxygen Pulse Oxygen Pulse: “...the amount of oxygen consumed by the body from the blood of one systolic discharge of the heart.” Henderson and Prince Am J Physiol 35:106, 1914 Oxygen Pulse = VO 2 / HR Fick Equation: VO 2 = SV x HR x C(a-v)O 2 VO 2 /HR = SV x C(a-v)O 2 Oxygen Pulse ~ SV

34. Interpretation of CPET Peak oxygen consumption Peak HR Peak work Peak ventilation Anaerobic threshold Heart rate reserve Breathing reserve

35. Heart Rate Reserve Comparison of actual peak HR and predicted peak HR = (1 – Actual/Predicted) x 100% Normal <15%

36. Estimation of Predicted Peak HR 220 – age  For age 40: 220 - 40 = 180  For age 70: 220 - 70 = 150 210 – (age x 0.65)  For age 40: 210 - (40 x 0.65) = 184  For age 70: 210 - (70 x 0.65) = 164

37. Breathing Reserve Comparison of actual peak ventilation and predicted peak ventilation  Predicted peak ventilation = MVV, or FEV 1 x 35 = (1 – Actual/Predicted) x 100% Normal >30%

38. Comparison CPET results Normal CHF COPD Predicted Peak HR150150150 Peak HR150140120 MVV10010050 Peak VO 2 2.01.21.2 AT1.00.61.0 Peak VE604049 Breathing Reserve40%60%2% HR Reserve0%7%20% Borg Breathlessness548 Borg Leg Discomfort885

39. Cardiac vs Pulmonary Limitation Heart Disease  Breathing reserve >30%  Heart rate reserve <15% Pulmonary Disease  Breathing reserve <30%  Heart rate reserve >15%

40. CPET Interpretation Peak V O 2 HRR BR AT/V O 2 max A-a Normal >80% 30% >40% normal Heart disease 30% <40% normal Pulm vasc dis 30% <40% increased Pulm mech dis 15% 40% increased Deconditioning 15% >30% >40% normal

41. SUMMARY Cardiopulmonary measurements obtained at rest may not estimate functional capacity reliably. CPET includes the measurement of expired oxygen and carbon dioxide. The Borg scale is a validated instrument for measurement of perceptual responses. CPET may assist in pre-op evaluation and risk stratification, prognostication of life expectancy, and disability determination.

42. SUMMARY Cycle ergometer permits direct power calculation. Peak VO 2 is higher on treadmill than cycle ergometer. Peak VO 2 may be lower than VO 2 max. Absolute contraindications to CPET include unstable cardiac disease and SpO 2 <88% on RA. Fall in BP sys >20 mmHg is an indication to terminate CPET. 1 glucose yields 36 ATP in slow twitch fiber, and 2 ATP + 2 lactic acid in fast twitch fiber. RER= CO 2 produced / O 2 consumed

43. SUMMARY Above the anaerobic threshold, CO 2 production exceeds O 2 consumption. Ventilation will disproportionately increase at lactate threshold to eliminate excess CO 2. AT may be determined graphically from V slope method or from ventilatory equivalent for CO 2. Derived from the Fick equation, Oxygen Pulse = VO 2 / HR, and is proportional to stroke volume. In pure heart disease, BR is >30% and HRR <15%. In pure pulmonary disease, BR is 15%.