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Piergiuseppe Agostoni, MD, PhD

Physiological bases of clinical exercise testing: choosing and performing the proper test. Piergiuseppe Agostoni, MD, PhD Centro Cardiologico Monzino, Istituto di Cardiologia, Università di Milano, Milano Division of Respiratory Disease, University of Washington, Seattle, WA.

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Piergiuseppe Agostoni, MD, PhD

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  1. Physiological bases of clinical exercise testing: choosing and performing the proper test Piergiuseppe Agostoni, MD, PhD Centro Cardiologico Monzino, Istituto di Cardiologia, Università di Milano, Milano Division of Respiratory Disease, University of Washington, Seattle, WA.

  2. Ventilation Gas diffusion Cardiac output muscle O2 extraction O2 transport

  3. Why a cardiopulmonary exercise test? • Etiology of exercise limitation is unknown • Disease prognosis (CHF) • Effectiveness of therapeutic intervention • Exercise prescription • Transplant evaluation • Research!

  4. Cardiopulmonary exercise test Modalities • GAS ANALYSIS (indirect calorimetry) • Douglas bag procedure • Time-averaged systems • Breath-by-breath systems • ERGOMETER • Treadmill • Cycloergometer • Armometer

  5. Hystorical Easy to be performed VO2max > 5-10% Expensive, noisy Dangerous for some categories of patients Not suitable for hemodynamic measurements Difficulties in assessing workrate Easy to assess workrate Less expensive, less noise Easy to assess VO2/WR Suitable for hemodynamic measurements VO2max 89%-95% vs treadmill Treadmill Cycloergometer

  6. Costant Workload Step Incremental Workload Ramp Incremental Workload Cardiopulmonary Exercise Test Protocols

  7. CONSTANT WORKLOAD PROTOCOLS VO2 3’ 6’ Time • Gas kinetics Analysis • - phase 1 linked to cardiac output • - phase 2 related to exercise capacity • (Tau: 63% VO2max; T1/2) • - phase 3 (Delta 6°e 3° minute) • Above or below Anaerobic Threshold • Response to therapeutic intervention

  8. INCREMENTAL PROTOCOLS Zhang et al. Did the different work rate step patterns affect aerobic function parameters? Ramp 2-min step VO2 (L•min-1) Work Rate (W) 1-min step 3-min step Time (min)

  9. What is a Ramp Protocol? • Constant and continuous work increases • Can be easily individualized • Test duration may be better targeted • May better elicit a “true” VO2max • 2’-3’ step incremental protocol useful only if intermediate steady state needing (i.e. blood sampling, haemodinamic measures)

  10. CARDIOPULMONARY EXERCISE TEST OPTIMAL LENGHT J Appl Physiol 1983 - What is the ideal maximal exercise test? Mode that progressively increases total body and myocardial demand in reasonable time - What is an optimal time duration?8 to 12 minutes

  11. Effects of work-rate ramp on peak exercise parameters in heart failure They are influenced Peak WR Watts Peak VO2 ml/min/Kg * * * * * Agostoni PG et al. Eur J Heart Fail 2005

  12. Effects of work-rate ramp on AT parameters in heart failure Work rate AT Watts VO2 AT ml/min/Kg It is not influenced It is influenced * * * Agostoni PG et al. Eur J Heart Fail 2005

  13. Effects of work-rate ramp on VE/VCO2 slope in heart failure It is not influenced Agostoni PG et al. Eur J Heart Fail 2005

  14. It is influenced >VO2/WR slope > lenght Effects of work-rate ramp on VO2/WR slope in heart failure Agostoni PG et al. Eur J Heart Fail 2005

  15. Match the Person, Protocol, and Purpose of the Test !!!! • Major Parameters.

  16. CARDIOPULMONARY EXERCISE TEST: WHICH MEASUREMENTS DOES IT SUPPLY? Wasserman K. Priciples Exercise Testing and Interpretation. Third Edition Lippincott Williams & Wilkins

  17. VO2max VO2 = SVxHRx a-vO2diff

  18. VO2/WORK SLOPE • O2 consumption vs work • match o2 delivery and o2 utilization.

  19. VO2/ WR Clinical Relevance VO2 obese normal CAD, MI CHF, reduced O2 utlization Work N.V. 10 ml/min/W • Position (ie overweight) • slope (ie heart failure) • Linearity (ie coronary artery disease)

  20. O2 Pulse • It reflects SV and… • is affected by: • - anemia • - hypoxemia • - heart failure • - deconditioning HD: heart disease; OAD: obstructive airway disease O2Pulse = SVxHRx a-vO2diff HR

  21. ANAEROBIC THRESHOLD IDENTIFICATION V-SLOPE METHOD Normal >40% del V’O2 MAX

  22. BEHIND ANAEROBIC THRESHOLD IDENTIFICATION

  23. END OF RESPIRATORY COMPENSATION IDENTIFICATION

  24. ! VE/VCO2 SLOPE Ventilatory Efficiency overestimated VE/VCO2 slope

  25. Tidal volume & Respiratory frequency • VT •  non-linearly • may plateau in some • ventilatory limitation • VT > 55% of VC • RF • slow  initially • sharp  • hyperventilation • ventilatory limitation • RR > 55 b/min k x VCO2 [PaCO2 x (1-Vd/Vt)] VE=

  26. …beyond VO2… the future of CPET…

  27. Piergiuseppe Agostoni, MD, PhD Gaia Cattadori, Anna Apostolo, Mauro Contini, Pietro Palermo, Giancarlo Marenzi, Karlman Wasserman.

  28. Fick VO2 = VE (FiO2 – FeO2)VO2 = Q (CaO2 – CvO2)VO2 = D (PcapO2 – PmitO2)

  29. a) Cardiac outputb) A-V O2 difference- hemoglobin- Hb O2 sat- pO2

  30. Cardiac Output (L/min) A-V Content Difference (ml/100 ml)

  31. Anemia Healthy + Hb Healthy COPD Cardiac Output (L/min) HF A-V Content Difference (ml/100 ml)

  32. CO estimated noninvasively from oxygen uptake during exercise. Stringer WW et al. J Appl Physiol. 82(3): 908-912

  33. Method: INERT GAS REBREATHING • Spontaneous rebreathe (for 10-20 sec.) from a bag prefilled with an oxygen enriched mixture containing two foreign gases • Nitrous oxide (N2O) is soluble in blood and its concentration decreases during rebreathing with a rate proportional to CO • Sulphur hexafluoride (SF6) is insoluble in blood and is used to determine the lung volume Population: 20 CHF pts (VO2max 16.62.9 ml/min/Kg) • Study Design: • CPET (ramp protocol) to assess functional capacity • CPET (incremental protocol) with CO determination at each step by • - Inert Gas Rebreathing method (R) • CPET (incremental protocol) with CO determination at each step by • - Inert Gas Rebreathing method (R) • - Direct Fick method • - Thermodilution method

  34. R vs T R= 0.94 F vs T R= 0.95 R vs F R= 0.95 Agreement (vs Fick and vs Thermodilution) Conclusions: In CHF CO measurement during exercise by Inert Gas Rebreathing technique provides repeatable measurements that agree with Direct Fick and Thermodilution methods

  35. VO2 Pred = 1676 VO2 Measured 947 (57%) 22 20 18 16 14 VO 12 2 (L/min) Cardiac Output (L/min) 10 1,5 8 6 1 4 0,5 0,3 2 0 0 2 4 6 8 10 12 14 16 18 20 Artero-venous oxygen difference (ml/100ml)

  36. 22 20 PRE riab VO2p=713 (8.6) POST riab VO2p=806 (9.7) 18 16 14 VO 12 2 (L/min) Cardiac Output (L/min) 10 1,5 8 6 1 4 0,5 0,3 2 0 0 2 4 6 8 10 12 14 16 18 20 Artero-venous oxygen difference (ml/100ml)

  37. 22 20 PRE riab VO2p=911 (12.7) POST riab VO2p=1413 (19.6) 18 16 14 VO 12 2 (L/min) Cardiac Output (L/min) 10 1,5 8 6 1 4 0,5 0,3 2 0 0 2 4 6 8 10 12 14 16 18 20 Artero-venous oxygen difference (ml/100ml)

  38. However, we have to account for Cardiac Output distribution, exercise hemoconcentration and anemia…

  39. Agostoni et al Am J Cardiol 2001

  40. CO distribution improves in severe HF Agostoni et al Am J Cardiol 2001

  41. STUDY SAMPLE 21 patients with thalassemia intermedia 10 with previuos splenectomy Agostoni PG et al. Brit J Haematol 2005

  42. Without splenectomy Splenectomized *p<0.01 vs pts without splenectomy Agostoni PG et al. Brit J Haematol 2005

  43. How much is anaemia relevant ?if Hb sat 100%CaO2 = 1.34 ml x gr Hbif peripheral O2 extraction 70% 1 gr Hb provides to the tissues 1 ml O2 x dl of blood.

  44. ….clinical use

  45. Step CO L/min HR b/min SV ml/b VO2 ml/min Diff AV Basal 5.9 90 66 208 3.5 40 % 10.1 101 100 1155 11.4 Peak 15.3 166 92 2310 15 Peak pred 16.6 169 98 2695 16.4 Peak % 92 98 94 86 91 VO2max predicted 2695 (ml/min) HRmax predicted 169 (b/min) COmax predicted 16.6 (L/min) {(≥5xVO2)+3} Hb predicted 15 (g/dl) diffAV predicted 16.4 (ml/100ml)

  46. Hb 15 gr/dl ml VO2 due to anemia 0 ml ml VO2 due to deconditioning [(16.4-15.0)x153]=214 ml ml VO2 due to CO 166 – 153 = 13 x 16.4 = 213 ml Deficit VO2 calcolated 427 ml/min Deficit VO2 observed 385 ml/min  • CONCLUSIONS: Test indicative of good functional capacity (VO2 max 86% of the predicted). Minimal deficit due to: • anemia (0%) • deconditioning (50%) • cardiogenic (50%)

  47. Step CO (L/min) HR (b/min) SV (ml/b) VO2 (ml/min Diff AV Basal 4.5 75 60 220 5 40 watt 5.9 102 58 604 10 Peak 7.9 109 72 1080 14 Peak pred 13.6 154 88 2120 16 Peak % 58 71 82 51 88 VO2max predicted 2120 (ml/min) HRmax predicted 154 (b/min) COmax predicted 13.6 (L/min) {(≥5xVO2)+3} Hb predicted 15 (g/dl) diffAV predicted 16 (ml/100ml)

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