Cardiopulmonary Stress Testing: Beyond Transplant Evaluation

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Cardiopulmonary Stress Testing: Beyond Transplant Evaluation Ross Arena, PhD, PT, FAHA, FESC, FACSM Professor and Head College of Applied Health Sciences University of Illinois at Chicago

Cardio- Pulmonary Pulmonary Arterial Circuit Pulmonary Venous Circuit O 2 O 2 CO 2 Interface Left Atrium- Ventricle CO 2 Right Atrium- Ventricle Chemo/ Ergo Receptor and ANS Balance Skeletal Muscle O2 Systemic Arterial Circuit CO 2 Myers et al, Curr Prob in Card, In Press Systemic Venous Circuit

Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association by Robert Ross, Steven N. Blair, Ross Arena, Timothy S. Church, Jean-Pierre Després, Barry A. Franklin, William L. Haskell, Leonard A. Kaminsky, Benjamin D. Levine, Carl J. Lavie, Jonathan Myers, Josef Niebauer, Robert Sallis, Susumu S. Sawada, Xuemei Sui, and Ulrik Wisløff Circulation Volume 134(24):e653-e699 December 13, 2016 Copyright American Heart Association, Inc. All rights reserved.

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The value of gas exchange beyond aerobic capacity The real why. 7

Ventilatory Efficiency 8

The relationship between pulmonary hypertension pathophysiology and cardiopulmonary exercise testing markers Pinkstaff SO, Burger CD, Daugherty J, Bond S, Arena R. Guidelines for the Use of Cardiopulmonary Exercise Testing in Patients with Pulmonary Hypertension: Evidence-Based Recommendations. Expert Review of Respiratory Medicine. 2016;10(3):279-95.

Comparison between normal and abnormal pulmonary arterial vessel response to exercise: implications for cardiac output with an acute exercise stimulus and right ventricular function with chronic exercise Arena R, Lavie CJ, Borghi-Silva A, Daugherty J, Bond S, Phillips SP, Guazzi M. Exercise training in group 2 pulmonary hypertension: Which intensity and what modality. Progress in Cardiovascular Disease. 2016 Jul- Aug;59(1):87-94.

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What is limiting clinical application and value?

PAH Normal 14

One dimensional Three dimensional VO 2 VO 2 VCO 2 VE More 15

Copyright American Heart Association

The Essentials Aerobic Performance Subjective Scales Ventilatory Efficiency ECG Pulmonary Function Hemodynamics 17

Universal CPX Reporting Form

Normal (dashed line) and abnormal (solid line) example of oxygen pulse and ΔVo2/ΔW plots Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Examples of normal ventilatory pattern (top panel) and exercise oscillatory ventilation pattern (bottom panel) Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Flow Volume Loops Copyright American Heart Association 21

Heart Failure Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

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Unexplained Exertional Dyspnea Guazzi M et al. Circulation and EHJ 2016 Copyright American Heart Association

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Improved Resolution for Unexplained Dyspnea Flow limitation: Flow rate during exercise = PFT flow rate Dynamic Hyperinflation: Increase in end expiratory lung volume (i.e. exercise induced air trapping)

Suspected or Confirmed PAH/Secondary PH Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Confirmed or Suspected HCM Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Prognostic and Diagnostic Stratification for Patients With COPD or ILD. Guazzi M et al. Circulation 2016 Circulation and EHJ

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Suspected Myocardial Ischemia Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Suspected Mitochondrial Myopathy Guazzi M et al. Circulation 2012;126:2261-2274 Copyright American Heart Association

Presurgical Assessment Guazzi M et al. Circulation 2016 Circulation and EHJ 35

Valvular Heart Disease/Dysfunction Guazzi M et al. Circulation 2016 Circulation and EHJ 36

Apparently Healthy Individuals Guazzi M et al. Circulation 2016 Circulation and EHJ 37

Rating Evidence and Clinical Recommendations 38

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Evidence of Certainty (Precision) of Prognostic Value LEVEL A Multiple populations evaluated Data derived from multiple prospective outcomes databases or meta-analyses LEVEL B Limited populations evaluated Data derived from single prospective outcomes database or retrospective databases LEVEL C Very limited populations evaluated Only consensus opinion of experts, small outcomes databases, or standard of care Suggested phrases for writing recommendations Class I Assessment/Measure(s) clearly prognostic Assessment SHOULD be performed or administered Recommendation that assessment/measure(s) is useful/effective Sufficient evidence from multiple prospective outcomes databases or meta-analyses Recommendation that assessment/measure(s) is useful/effective Evidence from single prospective outcomes databases or retrospective outcomes databases Recommendation that assessment/measure(s) is useful/effective Only expert opinion, small outcomes databases, or standard of care Should Is recommended Is indicated Is useful/effective/beneficial Level of Prognostic Significance Class IIa Assessment/Measure(s) likely prognostic Several Additional Level A studies needed IT IS REASONABLE to perform or administer assessment Recommendation in favor of assessment/measure(s) being useful/effective Some conflicting evidence from multiple prospective outcomes databases or meta-analyses Recommendation in favor of assessment/measure(s) being useful/effective Some conflicting evidence from single prospective outcomes databases or retrospective outcomes databases Recommendation in favor of assessment/measure(s) being useful/effective Only diverging expert opinion, small outcomes databases, or standard of care Is reasonable Can be useful/effective/beneficial Is probably recommended or indicated Class IIb Assessment/Measure(s) may be prognostic Greater number of additional Level A and B (preferably A) studies needed Assessment MAY BE be performed or administered Recommendation s usefulness/efficacy less well established Greater conflicting evidence from multiple prospective outcomes databases or meta-analyses Recommendation s usefulness/efficacy less well established Greater conflicting evidence from single prospective outcomes databases or retrospective outcomes databases Recommendation s usefulness/efficacy less well established Only diverging expert opinion, small outcomes databases, or standard of care May/might be considered May/might be reasonable Usefulness/effectiveness is unknown/unclear/uncertain or not well established Class III No benefit or Class III Harm No Benefit:Assessment/measure(s) not prognostic Harm: Assessment/measure(s) excess cost without prognostic insight or harmful Recommendation that assessment/measures(s) not useful/effective and may be harmful Sufficient evidence from multiple prospective outcomes databases or meta-analyses Recommendation that assessment/measures(s) not useful/effective and may be harmful Evidence from single prospective outcomes databases or retrospective outcomes databases Recommendation that assessment/measures(s) not useful/effective and may be harmful Only expert expert opinion, small outcomes databases, or standard of care No Benefit Is not recommended Is not indicated Should not be performed/administered/other In not useful/beneficial/effective 40

Class I Class IIa Class IIb Class III CPX is clearly: prognostic/diagnostic CPX clearly: gauges therapeutic efficacy CPX: - Should be performed - Is recommended - Is Indicated - Is Useful - Is Effective - Is Beneficial CPX is likely: prognostic/diagnostic CPX likely: gauges therapeutic efficacy CPX: - Is probably recommended - Is probably indicated - Can be useful - Can be effective - Can be beneficial CPX may be: prognostic/diagnostic CPX may: gauge therapeutic efficacy CPX: - May be considered - May be reasonable - Usefulness is unknown - Usefulness is unclear - Usefulness is uncertain - Usefulness is not well established CPX is not: prognostic/diagnostic CPX does not: gauge therapeutic efficacy CPX: - Has no benefit - Is not recommended - Is not indicated - Should not be performed - Should not be administered - Is not useful - Is not beneficial - Is not effective 41

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Future Considerations 45

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Refining the Algorithms Based of Hazard Ratio VE/VCO 2 slope = 7 HRR = 5 OUES = 3 P ET CO 2 = 2 Peak VO 2 = 2 48

Submaximal Testing 49

OUES 50

Translation from Science to Practice http://www.ncats.nih.gov/research/cts/cts.html 51

Lab of the Future: Comprehensive Functional Assessment CPX IMS&E MFP&E 52

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