Section Three: Cardiopulmonary Exercise Testing: Indications, Interpretation & Case Examples

The Cardiopulmonary Exercise Test

Introduction

The Cardiopulmonary Exercise Test (CPET) is an extremely valuable but underutilized non-invasive examination. The Exercise Health and Sports Cardiology Committee would like to promote CPET as an effective tool in evaluating cardiac function.

Physical activity requires the integrated performance of cardiovascular, pulmonary, metabolic, and neuromuscular systems. The Cardiopulmonary Exercise Test (CPET or CPX) evaluates the concerted response of these systems during exercise and provides an assessment of each component required for exercise performance. In contrast to standard exercise test modalities, the defining element of CPET is the continuous measurement of ventilation and gas exchange.

The relationship between oxygen consumption and carbon dioxide production and a vast array of non-invasive physiological parameters are used to determine the function of each component of physical exertion. From rest, through moderate exercise, to exhaustion, CPET enables an evaluation of overall capacity of the subject and the physiologic integrity of each system from ventilation, to circulatory transport, to tissue uptake. Although the significance of disturbances in the relationships between physiologic systems measured during CPET may be initially daunting, the utility and indications for this test are important and easy to understand.

Cardiopulmonary fitness is determined by measuring oxygen uptake (V̇O₂) at maximal exercise, while the ventilatory (anaerobic) threshold (VT) occurs at a submaximal point during exercise when pulmonary ventilation increases disproportionately to oxygen uptake. Cardiovascular limitations are exemplified by low values for peak V̇O₂ and ventilatory threshold. The ratio of oxygen uptake to work rate is reduced due to an impaired ability of the cardiopulmonary system to provide oxygen to the working muscles. A low stroke volume may be reflected by a low peak V̇O₂ per heart beat (O₂ pulse). Pulmonary limitations that may result in a reduced V̇O₂ are revealed by an abnormal breathing reserve, oxygen desaturation, CO₂ retention, or abnormal expiratory flow rate.

Peripheral myopathy is suggested by a low peak V̇O₂ , with an elevated minute ventilation to V̇O₂ ratio and a high cardiac output to V̇O₂ slope. Further discrimination of the cause of exercise intolerance can be determined by evaluating the relationships between additional variables. Endurance athletes commonly will have findings on CPET that may be considered abnormal in the sedentary population. These athletes may have higher peak V̇O₂ , higher anaerobic threshold, a high O₂ pulse reflecting a higher stroke volume and a maximum exercise ventilation that nearly matches the maximum voluntary ventilation, such that the breathing reserve is nearly zero given their exceptionally high cardiovascular capacity.

Figures 1-9   Sample findings in CPET Testing

Indications

Dyspnea of unknown etiology

CPET can help differentiate between pulmonary, cardiac, neurologic, muscular and psychological basis of dyspnea that limits exercise performance.

Diagnosis and assessment of the severity of organ dysfunction, relative compensatory contributions of other organ systems, prognosis, sequential monitoring in the following disease processes.

Cardiac

Heart Failure with reduced ejection fraction
Heart Failure with preserved ejection fraction
Valvular Heart Disease
Hypertrophic Cardiomyopathy
Congenital Heart Disease: Persons with CHD often have abnormal recognition of DOE
Coronary Artery Disease.

Pulmonary

Pulmonary Artery Hypertension
Secondary Pulmonary Artery Hypertension
Chronic Obstructive Pulmonary Disease
Interstitial Lung Disease

Neuro-muscular

Mitochondrial Myopathy
Neuromuscular Disease
Chronic Fatigue/ Post Exertional Malaise

Assessment of Surgical Risk

CPET responses have been increasingly applied to stratify risk as part of pre-surgical assessment. For example, peak V̇O₂ strongly predicts risk for surgical complications, length of hospital stay, and ability to return to work across a wide spectrum of surgical interventions.

Development of Cardiac or Pulmonary Rehabilitation exercise prescriptions and guidelines

The foundation of an appropriate exercise prescription in a patient with cardiovascular or pulmonary disease is the exercise test, and because of its superior precision, the CPET provides the most accurate method to develop an individualized exercise prescription.

Assessment of safety and metrics for an exercise training program

The CPET provides a wealth of information on safety, rhythm abnormalities, ischemic responses, and symptoms that are important in developing a safe and appropriate exercise prescription.

Assessment of cardiorespiratory fitness and subsequent response to a training program or interventions in healthy individuals, athletes or those with underlying cardiovascular disease (as listed above)

The CPET provides an accurate metric to quantify changes in fitness in response to exercise training and other interventions (eg. drug, surgical or device) among both healthy individuals and those with cardiovascular disease.

How to Perform a Cardiopulmonary Exercise Test

CPET test administration requires specific equipment and personnel in order to generate accurate and reliable data.

Equipment

• Ergometer (cycle, treadmill, rowing simulator, etc)
• Gas exchange mask/mouthpiece
• Metabolic cart consisting of gas analyzers, expiratory gas flow and volume, and software
  
• Continuous electrocardiogram
  
• Blood pressure measurement device

Personnel

• Exercise physiologist to set up the exercise protocol, prepare/calibrate equipment and possibly monitor during the test
  
• Medical assistant or nurse to monitor during the test
  
• Qualified medical professional for interpretation of the test

Many patients can be tested on a cycle ergometer or treadmill, based on comfort level and lab availability. If testing athletes, the type and intensity of the test protocol should be matched to their sport (ex: having a sprinter perform sprints on a treadmill or a rower using the rowing ergometer) which will provide more useful test results. Cycle tests are logistically easier for monitoring blood pressure and generate electrocardiogram tracings with fewer artifacts and unstable baselines.

The exercise protocol will vary depending on the interview conducted by the ordering provider. Common exercise protocols include the step protocol (ex: Bruce-type protocol), with a step-wise or incremental increase in work rate over time, or a ramp protocol with a continuous increase in work rate over time. The exercise test should be individualized by the exercise physiologist or medical provider administering the test with a target test time between 8-12 minutes.

Key Metrics

Heart rate, blood pressure, and electrocardiographic responses to exercise should be evaluated in a similar fashion as a routine exercise test

Ventilation and Gas Exchange: Measured throughout exercise

Maximum V̇O₂ : This is the aerobic capacity or total body oxygen uptake verified by achieving a heart rate within 10 bpm of the age-predicted HRmax, a lack of change in the V̇O₂ over two consecutive work rates, and/or a respiratory exchange ratio above 1.10 (presumably reflecting a lactate accumulation above 70-80 mg/dl). If these criteria cannot be met, the oxygen uptake at maximally tolerated exercise is referred to as peak V̇O₂ . V̇O₂ is often a metric that is tracked over time to monitor treatment or interventions as well as to monitor disease progression or prognosis.
V̇CO₂: Carbon dioxide elimination measured throughout the test.

Lactate Threshold V̇O₂ ≈ Anaerobic Threshold ( AT ) ≈ Ventilatory Threshold ( VT ): V̇O₂ above which lactate accumulates in the blood. This may be a useful marker of an individual’s cardiorespiratory fitness and endurance. Often referred to as anaerobic threshold or ventilatory threshold. Can be determined by ventilatory analogs of lactate accumulation such as V̇O₂ vs V̇CO₂ and V̇E vs V̇O₂ graphs. 

Respiratory exchange ratio (RER): The ratio of CO₂ produced to oxygen consumed (V̇CO₂/V̇O₂). A marker of fuel utilization (0.70 ≈ fat utilization and ≥1.0 ≈ carbohydrate utilization). Also a reflection of the degree of physiologic effort (≥1.10 associated with maximal effort)

Oxygen Pulse (V̇O₂ /HR): Will increase at the beginning of exercise largely due to the increase in stroke volume and then will reach a plateau near the end of exercise. If this plateau is reached sooner than expected, it can be due to impaired oxygen extraction or impaired stroke volume (due to CAD or left ventricular dysfunction).

Pulmonary Ventilation (V̇E): Volume of air exhaled per unit time. Generally not a limiting factor unless there is a low breathing capacity or a disease state that impairs air flow.

Change in V̇O₂ /change in work rate: This generally has a linear relationship of 10 mL/min of oxygen uptake for every 1 Watt increase in work rate. This relationship may change in illnesses such as cardiovascular diseases where oxygen uptake may be decreased compared to change in work rate.

Heart rate recovery: Reflection of vagal reactivation. Slow heart rate recovery associated with higher adverse outcomes. Often expressed as 1-minute post exercise (HRR1) or 2-minutes post exercise (HRR2). HRR1 <12 beats/min or HRR2 <22 beats/min associated with higher risk.

V̇E/V̇CO₂: Can be expressed as a ratio (at a point in time during exercise) or as the slope of the change during exercise. Reflects ventilatory efficiency, ie. the ventilatory requirement to eliminate a given amount of CO₂, and is a strong prognostic marker.

Oxygen uptake efficiency slope (OUES): The relation between the change in oxygen uptake during exercise and the log of the change in ventilation. The OUES is another measure of ventilatory inefficiency, and is a strong predictor of prognosis in patients with heart disease.

Perceived exertion: A reflection of the degree of the individual’s physical effort. Often expressed using a 6-20 scale, with 6 representing a resting state and 20 representing maximal effort.

Cardiopulmonary Exercise Test Cases

Case Study – Heart failure

History:

The patient is a 60 year old sedentary Caucasian male outpatient 71 inches tall, weighing 180 lbs. He is currently not smoking but has 23 pack years of smoking (1 pack/day for 23 years). The patient’s weight is normal (BMI=25). A history of abnormal lipids was reported (high TC, LDL, low HDL). The patient also has a history of high blood pressure. He over the past 6 months has noted increasing shortness of breath with exertion.

Reason for Referral:

Evaluation of increasing shortness of breath with regular daily activities.

Past Medical History:

There is a history of “mildly reduced ventricular function”, diagnosed approximately 6 years ago, although no imaging results are available. He reports infrequent “skipped beats”. No other history of non-cardiac or other medical problems are noted. Current medications include an ACE inhibitor, statin, and diuretic.

CPX Test Results:

Rest:

ECG: Normal sinus rhythm and left bundle branch block. 

Pulmonary Function: Forced vital capacity is 3.50 L (79% of expected) and the FEV1/FVC is 50% (Normal > 75%).

Heart rate: 71

Blood pressure: 112/68

Key items:

• Peak RER and perceived exertion suggest maximal effort
• Limiting symptom was dyspnea; no chest discomfort reported
• Severely impaired exercise tolerance (40.4% of age-predicted peak VO2) 
• Exercise ECG not analyzable due to LBBB; infrequent PVCs occurred
• Normal heart rate and blood pressure response; impaired heart rate recovery at 1 and 2 min post exercise
• Ventilatory threshold occurred at low VO2 (7.7 ml/kg/min) but normal percentage of peak  
• Normal breathing reserve; high VE/VCO2 slope and low OUES suggest ventilatory inefficiency
• Low peak O2 pulse; plateau beginning ≈50% of peak
• Abnormal resting PFTs suggest airflow limitation and possible pulmonary contribution to exercise intolerance

Conclusion

• Severely impaired exercise tolerance 
• Early dyspnea during exercise and daily activities, ventilatory inefficiency suggest impaired cardiac output
• Higher than normal risk for age indicated by severely impaired peak VO2, heart rate recovery, and indices of ventilatory inefficiency

References

Myers J, Arena R, Cahalin L, Labate V, Guazzi M. Cardiopulmonary exercise testing in heart failure. Current Problems in Cardiology 40:322-372, 2015.

Malhotra R, Bakken K, D’Elia E, Lewis GD. Cardiopulmonary exercise testing in heart failure. JACC Heart Fail 4:607-16, 2016.

Balady GJ, Arena R, Seitsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian S, Lavie CJ, Macko R, Mancini D, Milani RV. A Clinician’s  Guide to Cardiopulmonary Exercise Testing. A Scientific Statement from the American Heart Association. Circulation 122:191-225, 2010.

Case Study – Coronary artery disease

History:

The patient is a 68 year old sedentary Caucasian male outpatient 65 inches tall, weighing 160 lbs. The patient is currently not smoking but has a 50 pack year history of smoking (2 packs/day for 25 years). The patient is 10 lbs over the average appropriate body mass index (BMI=26.6) which qualifies as overweight. A history of abnormal lipids was reported (high TC, LDL, low HDL). The patient also has a history of high blood pressure.

Reason for Referral:

Evaluation of chest pain

Past Medical History:

The patient has the following symptoms: shortness of breath with regular daily activities and occasional mild chest discomfort. There is no other history of cardiac disease, cardiac events or dysrhythmias. No other history of non-cardiac or other medical problems are noted. Current medications include a beta blocker, ACE inhibitor, statin, and diuretic.

CPX Test Results:

Rest:

ECG: Within normal limits

Pulmonary Function: Forced vital capacity 2.9 L (73% of expected) and the FEV₁/FVC is 53% (Normal > 75%)

Heart rate: 76

Blood pressure: 146/78

Key items:

• Peak RER and perceived exertion suggest maximal effort
• Impaired exercise tolerance (62% age-predicted peak VO₂ achieved)
• Exercise ECG shows 2.0 mm downsloping ST depression; resolved by 2 min recovery; no arrhythmias observed
• Chest discomfort (≈1 out of 4) at peak exercise resolved by 1 minute in recovery
• Chronotropic incompetence; impaired heart rate recovery
• Borderline breathing reserve; VE/VCO₂ slope and OUES suggest ventilatory inefficiency; normal O₂ sat
• Flattening of O₂ pulse beyond ≈50% VO₂

Conclusion

• Exercise intolerance attributable to high likelihood of CAD (ischemic ECG changes, chest pain, plateau of O₂ pulse)
• Pulmonary involvement suggested by low FEV₁, limited breathing reserve, elevated VE/VCO₂ slope and reduced OUES
• CPET results suggest further evaluation for CAD is warranted

References

Chaudhry S, Arena A, Hansen JE, Lewis GD, Myers J, Sperling LS, LaBudde BD, Wasserman K. The utility of cardiopulmonary exercise testing to detect and track early-stage ischemic heart disease. Mayo Clin Proc 85:928-932, 2010.

Balady GJ, Arena R, Seitsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian S, Lavie CJ, Macko R, Mancini D, Milani RV. A Clinician’s  Guide to Cardiopulmonary Exercise Testing. A Scientific Statement from the American Heart Association. Circulation 122:191-225, 2010.

Chaudhry S, Arena R, Bhatt DL, Verma S, Kumar N. A practical clinical approach to utilize cardiopulmonary exercise testing in the evaluation and management of coronary artery disease: a primer for cardiologists. Curr Opin Cardiol 33:168-177, 2018.

Case Study – DYSPNEA OF UNKNOWN ORIGIN

HISTORY OF CURRENT COMPLAINT: Patient is a 62 y-o female who reports dyspnea on exertion of progressive intensity and frequency over the past eight months. She denies symptoms at rest and in self-care activities. Unable to climb a flight of stairs without stopping to catch her breath. Stopped exercising on her stationary cycle 4 months ago due to fatigue and SOB. She denies chest pain but reports occasional tightness or pressure when she is severely SOB.

REFERRAL: Dyspnea or unknown origin; is it cardiac, pulmonary, or deconditioning?

PAST MED HX: Four years ago, the patient had NSTEMI; symptoms were chest tightness, mid-scapular pain, and severe dyspnea. Two stents placed in culprit RCA. LAD and LCX with luminal irregularities. 90% stenosis in OM1 and OM2 treated medically. HTN, Type-2 DM, obesity; stopped smoking 8 years prior to NSTEMI. No asthma. PFTs two years ago with normal.  BMI above 30.0 for the past 20 years with recent 15-pound weight gain.

CPX TEST RESULTS: 

Exercise performance: 

   Time: 8:00         Watts: 80 (72% pred; mild deficit)

Reason for stopping: moderately severe dyspnea, chest tightness

Metabolic:

PeakVO2: 18 ml/kg/min (70% pred)

Anaerobic threshold: 52% peakVO2

VO2/Watts slope: 14 ml / Watt (normal = 8.7-11.9.9)

Cardiac:

HR @ peak exercise: 88% age-predicted maximum

No ECG changes: no ectopy or dysrhythmia

BP response: adaptive, mildly hypertensive

HR/VO2 slope: 3.6 beats/ml (normal = 3.0-4.0)

VO2/HR (analog of stroke volume: low-normal

Ventilation:

    Vemax: 42 L/min tidal volume (Vt) 70% pred High ventilation frequency (Vf)

PetCO2: 45 mm Hg

Exercise Flow-Volume Loops: patient ventilated low in her forced vital

capacity (FVC), leaving 1.5 L of her Inspiratory Reserve Volume (IRV)

unused for tidal breathing. At peak exercise, performed 75% of each

exhalation in the Zone of Effort Independent Flow Limitation.

KEY CPX VARIABLES: 

• A cardiac basis of patient’s symptoms is ruled out:

PeakVO2 is only mildly reduced

Oxygen-pulse is low-normal consistent with a normal stroke volume

• Patient is deconditioned:

Low AT and elevated VO2/Watts

• Ventilatory Pattern is abnormal and the basis of patient’s dyspnea:

Fast Vf with reduced Vt; the result of forced expiratory efforts limited by

progressively collapsing small airways as the patient ventilated low in her

FVC. This abnormal ventilatory pattern invariably creates sensation of

SOB and may result in CO2 retention as demonstrated by this patient.

CONCLUSION: Patient’s dyspnea is pulmonary in origin. Patient is deconditioned.

SUGGESTED READING:

Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp BJ. Clinical Exercise Testing: Principles of Exercise Testing and Interpretation Including Pathophysiology and Clinical Applications. Philadelphia: Lippincott Williams and Wilkins, 2012.

Huang W, Resch S, Oliveira RK, Cockrill BA, Systrom DM, Waxman AB. Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center. Eur J Prev Cardiol. 2017;24(11):1190–1199.

Arena R Sietsema KE. Cardiopulmonary exercise testing in the clinical evaluation of patients with heart and lung disease. Circulation. 2011;123(6):668–680.

Case Study -CHRONIC FATIGUE SYNDROME (CFS)/ POST-EXERTIONAL MALAISE (PEM)

HISTORY OF CURRENT COMPLAINT: Patient is a 52 yo female who reports weakness in arms and legs for the past 14 years. Over the past 4 years, she has experienced profound fatigue after mild activity that may last for days. She discontinued using her stationary cycle two years ago. She felt compelled to quit her job due to fatigue and weakness. When deeply fatigued, she has short-term memory deficits and a sensation she describes as “brain fog.”

REFERRAL: Two-Day CPX (24-hour interval) to document functional capacity on Test-1 and Test-2; identify bio-markers consistent with CFS/PEM.

PAST MED HX: Patient never smoked. No DM, HTN, hyperlipidemia, renal or pulmonary disorders. Muscle CK and inflammatory markers are negative. Normal echocardiogram. No previous exercise tests. Normal blood panel and Chem-7.

CXR is normal..

CPX TEST RESULTS: 

PFTs: normal pre- and post-exercise on both Test-1 and Test-2.

Exercise: Patient cycled to volitional exhaustion on a 10 Watt ramp protocol.

PeakVO2: Supra-normal peak VO2 in both tests.

Ventilatory threshold (V-AT): analog of lactate threshold (V-Slope method) was normal.

Cardiac: Patient achieved 88% age-predicted HRmax in both tests with normal

ECG; no ectopy or dysrhythmia, normal BP response.

Ventilation: Ventilatory response was normal and nearly identical in both Test-1

and Test-2: slope VE/VCO2 = 27, PetCO2 = 39-41.

KEY CPX VARIABLES:

• peakVO2: reduced by 12% in Test-2
• Maximal work rate: reduced by 14% in Test-2
• Work@V-AT: reduced by 9.5% in Test-2.
• VO2 per unit work: increased 8% in Test-2. The higher VO2/Watt in Test-2

reflects reduced mechanical efficiency, attributed by some clinicians to

muscle micro-injury, and possibly uncoupling of oxidative phosphoryl-

ation due to mitochondrial dysfunction created by test-1 exercise. These

changes are consistent with Post-Exercise Malaise (PEM), a principle

correlate of CFS.

CONCLUSION:  Exercise is limited by muscular fatigue, greater in Test-2, associated with reduced peakVO2, maximal work rate, work at V-AT, and an increased VO2 per unit work, consistent with PEM/CFS as described in the literature.

SUGGESTED READING:

Nelson M, Buckley JD, Thomson RL, Clark D, Kwiatek R, Davison K. Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in myalgic encephalomyelitis / chronic fatigue syndrome.  J Trans Med 2019;17:80-88.

Stevens S, Snell S, Stevens J, Keller B, Van Ness JM. Cardiopulmonary exercise test methodology for assessing exertion intolerance in myalgic encephalomyelitis / chronic fatigue syndrome. Frontiers in Pediatrics 2018;6:242.

Snell CR, Stevens SR, Davenport TE, Van Ness JM. Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Physical Therapy 2013;93(11):1484-1492.

Case Study – EXERCISE PRESCRIPTION and TRAINING

History

HISTORY: Patient is a 70 yo female who requests exercise evaluation and prescription in preparation for attempts to climb to base-camp on Mount Everest (17,500 feet) and Mount Kilimanjaro (19,341 feet). She denies chest discomfort when exercising.

REFERRAL: Assess peakVO2, ventilatory anaerobic threshold (V-AT), and optimal target HR six months prior to climbing events to provide training guidelines. Perform second CPX two weeks prior to the event to assess progress and status.

PAST MED HX: No HTN, hyperlipidemia, diabetes, pulmonary disease, cardiac disease. Never a smoker. BMI = 22.48. She is active and participates in Pilates and Zumba exercise classes.

CPX TEST RESULTS:  10 Watts ramp cycle protocol

KEY CPX VARIABLES

• Maximal work capacity (Watts) increased 13.5%
• VO2 at the V-AT increased 15.7%
• Work (Watts) at V-AT increased 25%
• HR at V-AT increased 8.5%
• Oxygen-pulse (analog of stroke volume) increase 10.8%
• Target HR for training based on Test-1 data is 130-140 77-83% measured HRmax-; target derived from Test-2 is 140-150 (83-88% measured HRmax) maintaining patient between 0-8% of V-AT. 

CONCLUSION:

Patient’s baseline (Test-1) indicates an exceptional fitness status:

• Maximal work capacity is 131% of the age-predicted value
• peakVO2 is 108% age-predicted value
• HRmax is 109% age-predicted value
• V-AT occurred at 60 Watts, 79% of age-predicted maximal work capacity 

Training at the prescribed target intensities;

• Oxygen pulse was increased by 10.8% with less than 2% change in max HR achieved suggesting an increase in stroke volume.
• Work at V-AT was increased 25% while VO2 @ V-AT was increased by 15.7%, creating a greater range of activity that may be performed before onset of anaerobic metabolism.
• Maximal work capacity (Watts) increased 13.5% with an increase in peakVO2 of 7.4%.
• Slope of VO2 / Watt increased by 25%, consistent with increased oxygen utilization in active tissue 

SUGGESTED READING:

Weltman A, Weltman J, Rutt R, Seip R, Levine S, Snead D, Kaiser D, Rogol A. Percentages of Maximal Heart Rate, Heart Rate Reserve, and V̇O2peak for Determining Endurance Training Intensity in Sedentary Women. Int J Sports Med 1989; 10(3):212-216. DOI: 10.1055/s-2007-1024903

Henritze J, Weltman A, Schurrer RL, Barlow K. Effects of training at and above the lactate threshold on the lactate threshold and maximal oxygen uptake

European Journal of Applied Physiology and Occupational  Physiology. 1985; 54: 84–88.

Luciene F. Azevedo, Patrícia S. Perlingeiro, Patrícia C. Brum, Ana Maria W. Braga, Carlos E. Negrão & Luciana D. N. J. de Matos (2011) Exercise intensity optimization for men with high cardiorespiratory fitness, Journal of Sports Sciences 2011;29(6):555-561, DOI: 10.1080/02640414.2010.549613.

American College of Sports Medicine. Guidelines for Exercise Testing and Prescription. Lippincott Williams & Wilkins; 10th Edition, 2017. 

Other CPET Resources: 

1. A Practicum: Cardiopulmonary Exercise Testing and Interpretation. Includes didactic lectures, small group tutorials, and laboratory demonstrations with CPET. Usually, 3 practicums are held each year, next tentatively scheduled for October 8-10, 2020.
2. Textbook: Principles of Exercise Testing and Interpretation 5th Edition. Authors: Karlman Wasserman, James E. Hansen et al. Marco Guazzi, Francesco Bandera, Cemal Ozemek, David Systrom, Ross Arena
3. Marco Guazzi, MD, PHD,a Francesco Bandera, MD, PHD,a Cemal Ozemek, PHD,b David Systrom, MD,c,d Ross Arena, PHDb, Cardiopulmonary exercise testing: what is its value? J Am Coll Cardiol. 2017 Sep, 70 (13) 1618-1636.
4. Guazzi M, Adams V, Conraads V, et al. EACPR/AHA Scientific Statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation. 2012 Oct;126(18):2261-2274. DOI: 10.1161/cir.0b013e31826fb946.