Introduction

New California Chapter Exercise Health And Sports Cardiology Committee
The American College of Cardiology’s California Chapter has established an Exercise Health and Sports Cardiology Committee in response to the growing need for evidence-based, standardized, comprehensive care for athletes. The committee aims to serve as a resource for consultative cardiovascular assessment of highly active individuals as well as a home for educational tools to aid in their assessment and management. This is our first educational endeavor which includes the following five sections listed in the menu with links to key subjects.

Sections Menu

Section One: Pre participation Evaluation of the Athlete’s Heart

1. Athlete Cardiovascular Risk Video Questionnaire
2. Suggestions for the Physician Performing the PPE
3. Pre participation exam (PPE) screening
4. Athlete COVID-19 Risk Questionnaire
5. Current Recommendations for Cardiac Evaluation during the COVID-19 Pandemic
6. Myocarditis and COVID-19 (Professional and Young Athletes)
7. COVID-19 Vaccines and Myocarditis

Section Two: Interpretation of the Athlete’s Electrocardiogram

1. Overview
2. Figures and Tables
3. ECG Examples

Section Three: Cardiopulmonary Exercise Testing: Indications, Interpretation & Cases

1. Introduction
2. Indications
3. How to Perform an Exercise Test
4. Key Metrics
5. Cardiopulmonary Exercise Test Cases

Section Four: Imaging of the Athlete’s Heart

1. To be determined

Section Five: Case Reports

1. Coronary Artery Disease
2. Chronic Fatigue Syndrome
3. Exercise Prescription and Training

Section One: Preparticipation Evaluation of the Athlete’s Heart: Questionnaire with Videos and Resources

Authors, Alphabetical Order 

• Gerald Bourne, MD, FACC, The Adaptive Behavior Institute, Kensington, Ca
• Elizabeth H. Dineen, DO, Cardiovascular Disease, University Of California, Irvine Health, School Of Medicine, Division Of Cardiology
• Victor Froelicher, MD, FACC, Stanford Sports Cardiology, Professor Emeritus Of Medicine, Palo Alto Veterans Affairs Health Care System 

Why should you be concerned with answering these scary questions? Sure, heart problems and their complications including death are rare in young athletes. But what if the causes of these conditions and their complications were known and we knew their warning signs? Your parents, relatives and coaches would like you to be able to play sports safely. Modern medicine has made tools available for screening and treating heart conditions so why not take advantage of them? The first step in doing so is to watch these videos and answer these questions as best you can. Studies have shown us that they can be clues for recognizing the first signs of heart conditions. Your answers to these questions will be summarized for you to take to your annual screening for participation in organized sports with some suggestions for your doctor or organization to consider prior to sports participation. Even if you don’t have any of these symptoms now, you now know that if they ever occur they should be reported. Please share this resource with your teammates.

Athlete Cardiovascular Risk Video Questionnaire

Print out this form and watch the videos before entering your answer. (Sam, this will be done on screen when you make modifications)
Videos are courtesy of the University of Texas Southwestern Medical Center (Dr. Benjamin Levine).Cardiovascular Risk Questionnaire

1. Have you ever had discomfort, pain, tightness, or pressure in your chest during exercise?

Watch Video, then check appropriate response on printed questionnaire. (Sam: when modified, response will be on screen, not printed)

Sam: Insert videos and text for questions 2 thru 5

5. Have you ever seen a doctor for a heart problem before?

Check appropriate response on printed questionnaire.

6. Has a doctor ever ordered testing for your heart, such as an EKG/ECG, x-ray, Echocardiogram, MRI or an exercise stress test?

Check appropriate response on printed questionnaire.

7. Has a doctor ever told you not to play sports before?

Check appropriate response on printed questionnaire.

8. Have you ever had an unexplained seizure?

Check appropriate response on printed questionnaire.

9. Do you take any performance supplements or energy drinks?

Check appropriate response on printed questionnaire.

Suggestions for the Physician Performing the PPE

The Physician is urged to View, Download, and/or Print this PDF

Pre Participation Exam (PPE) Screening

The PPE is widely advocated for all youth athletes engaged in competitive sports. This year, in order to screen for the possible consequences of COVID-19, all athletes should undergo a PPE that assesses current or past symptoms of the SARS-Coronavirus-2. Testing to exclude significant cardiopulmonary disease should be based on the algorithms provided below. Most organizations suggest individual screening by a qualified clinician ( or trainer ) who has an available cardiology ( or sports medicine ) consultant. Mass screenings would require precautionary measures in order to maintain physical distancing. All screening should follow guidelines outlined by the California Department of Public Health, including cleaning of equipment (eg., ECG machines and wires to electrodes). Among athletes with  definite or possible prior infection , the use of adjunctive testing including electrocardiography, cardiac biomarkers, non-invasive imaging, and exercise testing represent potential appropriate options, depending on clinical context such as concerning symptoms.

History of new cardiac symptoms is extremely concerning and may be difficult to distinguish from deconditioning which can be due to sheltering in place. Importantly, myopericarditis related to COVID-19 should be considered in athletes with a history of new onset chest pain/pressure (even in the absence of fever and respiratory symptoms), palpitations, exercise intolerance, and/or resting or exercise related excessive tachycardia. Comprehensive clinical evaluation, regardless of ECG findings, is indicated in athletes with new onset cardiovascular symptoms or exercise intolerance. COVID-19 affected myocardial tissue can promote cardiac arrhythmias, and a major aim of the PPE is to identify those at risk for cardiac arrhythmias. At Stanford, an inexpensive ECG patch that can be automatically interpreted for PVC burden in clinic is being evaluated for this purpose in athletes recuperating from COVID-19.

Athlete COVID-19 Risk Questionnaire

Though we were on the downsloping curve of the Pandemic, there appears to be natural seasonal surges or possibly exacerbations due to new genetic strains of SARS-Coronavirus-2  or other viruses.  Therefore, your Pre Participation exam ( PPE) must include questions regarding whether you have had COVID-19 or been exposed to it or other viral infections. The SARS-Coronavirus-2 (COVID-19) infection (as well as other viral agents) can cause damage to your heart (myopericarditis) even if you’ve only had minor exposure and not had any complaints or any symptoms. Screening for active or prior infection, with appropriate work up could prevent life threatening consequences during or after physical activity. Please complete this questionnaire, generate a pdf/copy of your responses and give it to your Doctor, coach or trainer.Covid Questionnaire for Young Athletes [View, Download, Print PDF]

Current Recommendations for Cardiac Evaluation during the Covid-19 Pandemic

Cardiac evaluation has been intensified and exercise recommendations revised during this pandemic due to concerns raised by the cardiac complications noted in severe cases of Covid-19. Even though severe cases of Covid-19 are rarely seen in younger individuals, the potential for cardiac complications remains a concern and can sometimes occur months after even mild or asymptomatic infections. As a medical community, our recommendations are empirical and must be adjusted as knowledge grows and testing techniques improve. The latest recommendation (October 2020) was commissioned by the ACC Council on Sports Cardiology who chose America’s most active and experienced Sports Cardiologists and Sports Medicine specialists with cardiology knowledge to develop the document. The recommendation has been published in a peer reviewed journal and is available as a ACC webex video. The recommendations are specific for High School athletes (Figure 1-1), College and Professional athletes (Adults, Figure 1-2) and Master athletes (Figure 1-3). The experts also recommended adapted criteria for Myocarditis (Table 1-1). They presented specific cautions regarding the routine use of Computer Magnetic Resonance Imaging (MRI or CMR) as part of post-COVID PPE algorithm until there is a better understanding of how to differentiate pathological changes from those due to exercise training. The risk level of symptoms is provided in Table 1-2. These experts have observed that cardiovascular consequences of Covid-19 are relatively mild and so when compared to initial recommendations at the beginning of the pandemic, they have lessened indications for cardiac testing prior to return to play.

SAM, insert the 3 figures here

Table 1-1. Adapted Criteria for Myocarditis and Sports Eligibility

Myocarditis (Probable Acute Myocarditis With Both of the Following Criteria)

1. Clinical syndrome, including acute heart failure, angina-type chest pain, or known myopericarditis of less than 3 months’ duration.

2. Otherwise unexplained increase in serum troponin levels, ECG repolarization abnormalities, arrhythmias or high-grade atrioventricular block, abnormal ventricular wall motion, or pericardial effusion. Additional cardiac MRI findings that suggest myocarditis.

Sports Eligibility Myocarditis Recommendations

1. Before returning to sports, athletes diagnosed with a clinical syndrome consistent with myocarditis should undergo a resting echocardiogram, ambulatory ECG monitoring, and an exercise test no less than 3 to 6 mo after the illness.

2. It is reasonable that athletes can resume training and/or competition if all of the following criteria are met:

    A. Ventricular systolic function has normalized.
    B. Serum markers of myocardial injury, heart failure, and inflammation have returned to normal levels.
    C. Clinically relevant arrhythmias are absent.

Table 1-2. Risk levels of Symptoms

1. Mild Symptoms

include anosmia, ageusia, headache, mild fatigue, mild upper respiratory tract illness, and mild gastrointestinal illness;

2. Moderate Symptoms

include persistent fever, chills, myalgias, lethargy, dyspnea, and chest tightness;

3. Severe Symptoms

include dyspnea, exercise intolerance, chest tightness, dizziness, syncope, and palpitations which often require hospitalization.

Myocarditis and COVID-19

It is assumed that the sport and exercise are performed consistent with the current level of physical distancing, appropriate hygienic measures and face mask guidelines. Age and severity of illness have been emphasized and should be taken into account when considering cardiovascular diagnostics. Note also that at this time the benefits of exercise far outweigh the risk of exercise-induced cardio-pulmonary damage in the young. Our committee promulgates these recommendations with the caveat that they may be superseded by other guidelines as new knowledge becomes available.

The pathology (fibrosis, inflammation and thrombosis) of damage to the heart and lungs has been demonstrated but the time course and severity is uncertain and appears to be mild in athletes. Also it is not certain to what degree exercise training can exacerbate the damage caused by the pathogen but the experience so far is that this appears to be minor.

Myocarditis and COVID-19 in Professional Athletes

The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease COVID-19 pandemic. Martinez et al reported a retrospective analysis of return to play cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men’s and women’s National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities. The study included 789 professional athletes (98.5% males) and the majority had prior symptomatic COVID-19. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; Five athletes (0.6%) had CMR imaging findings suggesting inflammatory heart disease (3 myocarditis; 2 pericarditis, that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation.

Myocarditis and COVID-19 in Young Athletes

As of June, 2021 we have a better understanding of the prevalence of myocarditis in competitive athletes diagnosed with Covid-19 thanks to two large prospective multicenter studies of collegiate athletes.

ORCCA, the first large study of young athletes positive for Covid-19, included 3,018 college athletes from 42 universities. Serum troponin tests, ECG, and echocardiography identified 15 athletes (15/3,018=0.5%) with possible cardiac involvement. In a subgroup of 198 athletes who underwent a primary CMR imaging screening strategy (unselected by the other tests), a higher proportion of athletes demonstrated definite, probable, or possible cardiac involvement (n = 6 [3.0% for primary CMR strategy vs 0.5% for primary conservative strategy]).

The Big Ten registry was the second study and included 13 major universities from the Big Ten athletic conference. The strategy mandated ECG, troponin testing, echocardiography, and CMR imaging for athletes with positive COVID-19 test results, regardless of prior symptomatic status. Of 2,461 athletes,1597 (64.9%) had the complete comprehensive screening testing, including CMR imaging without prior selection. They found that 37 (2.3%) of these athletes demonstrated diagnostic criteria for myocarditis by CMR imaging, including 20 (1.2%) with normal ECG, echocardiography, and troponin test results. This leaves 17 or 1% with these positive conservative test results who would not have been identified without CMR imaging (2.3% for primary CMR strategy vs 1% for primary conservative strategy). Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis. Variable ascertainment and unknown implications of CMR findings underscored the need for standardized timing and interpretation of cardiac testing. They propose that their CMR imaging data provide a complete prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection. 

Comparison of the results of a conservative testing approach (symptoms, troponin, ECG and echocardiogram) vs a CMR for all athletes with COVID-19 for detecting myocarditis is best estimated using data from the 2 largest studies summarized above.  The results are 3.0-2.3% for primary CMR vs 0.5-1% for primary conservative strategy.  A “CMR for all strategy” more than doubles sensitivity but it is not clear if this added yield from a very expensive test saves lives or lessens myocardial damage.  Any comparison of a CMR strategy to another approach will favor CMR if the images are both the test result and the gold standard. The more appropriate gold standard would be the clinical outcome of the athletes; ie, do they really develop myocardial damage and/or a bad clinical outcome such as death or heart failure?

 It is revealing to consider some of the factors/variables not incorporated in these 2 studies that could affect the conclusions:  

1. The test characteristics of the diagnostic elements to identify COVID-19 myocarditis symptoms, troponin, ECG and echocardiogram).
2. The relative importance and characterization of the symptoms of myocarditis (including chest pain, breathing abnormalities, palpitations and fatigue)
3. The test characteristics of the tests identifying the presence of the Sars-CoV-2 virus and how applied (nucleic acid amplification tests (NAATs) and antigen tests, nasal swab vs saliva, lab-based vs point of contact)
4. The timing of assessment relative to the diagnosis of COVID-19 (particularly lacking is data regarding the “long-hauler” phenomena)
5. The exact significance of the CMR findings reported in athletes (what is pathological and associated with long term damage and what is the result of exercise training?)
6. The virulence of the causative genomic variant of Sars-CoV-2 virus 

These considerations do not detract from the available data since they could not be controlled or assessed in these studies.  However, they emphasize the need for humility and an athlete-centered, shared decision-making approach to athletes.  Furthermore, these studies require longer follow up to determine the risk of death due to the markers of myocarditis.

In an excellent Editorial responding to the Big Ten study, Udelson et al summarized the available data on return to play after COVID-19 Infection. We agree with them that the current data support a conservative approach to cardiac testing as in the guidelines and that clinical judgement be applied to individual cases. We also emphasize the need for an athlete-centered, shared decision-making approach in the management of young athletes with myocarditis post COVID-19.  These findings are consistent with the COVID-19 experience at Stanford Sports Medicine.

COVID-19 Vaccines and Myocarditis

Since April 2021, there have been increased reports to the Vaccine Adverse Event Reporting System (VAERS) of cases of called myocarditis and pericarditis happening after mRNA COVID-19 vaccination (Pfizer-BioNTech and Moderna) in the United States. These reports are rare, given the number of vaccine doses administered, and have been reported after mRNA COVID-19 vaccination, particularly in adolescents and young adults. Most patients who received care responded well to medicine and rest and quickly improved.

The cases reported are mostly in male adolescents and young adults age 16 years or older, more often after getting the second dose of one of these two COVID-19 vaccines than after the first dose, typically within several days after COVID-19 vaccination. They can usually return to their normal daily activities after their symptoms improve, and the above guidelines for management of myocarditis should be followed.Overall crude reporting for myo/pericarditis ages 12-17 is 9.1 cases per million in females and 66 per million in males. Overall reporting for ages 18-24 is 5 per million in females and 56 per million in males.  The available outcome data indicate that patients generally recover from symptoms and do well.  The CDC continues to recommend COVID-19 vaccination for everyone 12 years of age and older, given the greater risk of COVID-19 illness and related, possibly severe complications than the cases associated with vaccines.

Section Two: Guidelines from International Recommendations for Electrocardiographic Interpretation in Athletes

Authors, Alphabetical Order 

• Gerald Bourne, MD, FACC, The Adaptive Behavior Institute, Kensington, Ca
• Elizabeth H. Dineen, DO, Cardiovascular Disease, University Of California, Irvine Health, School Of Medicine, Division Of Cardiology
• Victor Froelicher, MD, FACC, Stanford Sports Cardiology, Professor Emeritus Of Medicine, Palo Alto Veterans Affairs Health Care System
• Heather Shenkman, MD, FACC, Interventional and Preventive Cardiology, Tarzana, CA 

Overview

The present section will provide a succinct overview of the interpretation of the electrocardiogram (ECG) in the athletic population by providing select resources for a more comprehensive understanding of ECG changes occurring in athletes, supported by examples of abnormal findings.

This document does not serve to support or refute the case for pre-participation screening with an ECG, but rather as a resource to help those providers whenever they are faced with analyzing an athlete’s ECG, including team physicians, family medicine, sports medicine, cardiology, athletic trainers and others caring for athletic individuals.

SELECT ECG INTERPRETATION RESOURCES:
1. ECGs provided in this document with brief description. ECGs obtained from Dr. Vic Froelicher.
2. “International recommendations for ECG in the athlete” provides tables and figures that clearly delineate:

Figure 2-1: Normal and Abnormal ECG Findings [PDF]
Table 2-1: Definitions of ECG Findings [PDF]
Table 2-2: Evaluation Suggested in the Setting of these ECG Findings [PDF]

• Full article found here: or [PDF]
• For further practice, please reference the University of Washington ECG Modules
• Please find Uberoi and colleagues, “Interpretation of the Electrocardiogram of Young Athletes,” at this link or [PDF]
• Please find Parry-Williams and colleagues, “Current Understanding of the Electrocardiographic Manifestations of the ‘Athlete’s Heart,’  [PDF]
• Please find Abela and Sharma’s Abnormal ECG Findings in Athletes: Clinical Evaluation and Considerations at the following link or [PDF]

Read the JACC Article International Guidelines for Reading Athlete’s ECGs

Examples of ECGs found in Athletes

Collection of ECGs gathered using the Cardiac Insight’s 20/20 ECG recording system

Section Three: Cardiopulmonary Exercise Testing: Indications, Interpretation & Cases

• AUTHORS, ALPHABETICAL ORDER

• GERALD BOURNE, MD, FACC, THE ADAPTIVE BEHAVIOR INSTITUTE, KENSINGTON, CA
• ELIZABETH H. DINEEN, DO, ASSISTANT CLINICAL PROFESSOR, UNIVERSITY OF CALIFORNIA IRVINE, SCHOOL OF MEDICINE, DIVISION OF CARDIOLOGY
• JEFFREY H. DWYER, PHD, DEPARTMENT OF CARDIOLOGY, KAISER PERMANENTE MEDICAL CENTER, VALLEJO, CA
• VICTOR FROELICHER, MD, PROFESSOR OF MEDICINE, STANFORD UNIVERSITY, PALO ALTO VA MEDICAL CENTER, DIVISION OF CARDIOLOGY
• JONATHAN MYERS, PHD, EXERCISE PHYSIOLOGIST/CARDIOPULMONARY SPECIALIST, DIRECTOR, CARDIOPULMONARY RESEARCH, STANFORD UNIVERSITY, PALO ALTO VA MEDICAL CENTER

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.

View Slides in PDF Format

Indications

1. Dyspnea of unknown etiology

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

2. Diagnosis and assessment of the severity of organ dysfunction

• 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.

4. 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.

5. 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.

6. Assessment of cardiorespiratory fitness and subsequent response to a training program or interventions in healthy individuals, athletes or those with CV disease

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

• Modality

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.

• Protocol

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 One – Dyspnea on exertion, decreased exercise capacity

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

View Figures of Sample Findings in CPET Testing [pdf]

Primary Test Conclusions

• 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 V̇O₂ , heart rate recovery, and indices of ventilatory inefficiency

Additional Points

• 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 V̇O₂ )
• 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 V̇O₂ (7.7 ml/kg/min) but normal percentage of peak
• Normal breathing reserve; high V̇E/V̇CO₂ 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

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 2– 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

Ventilatory threshold
Exercise time	5:36
Heart rate	89
Oxygen uptake (ml/kg/min)	8.2
Oxygen uptake (ml/min)	868.4
VO2 % peak	71%

Peak Exercise	Reason for stopping – Shortness of breath (with slight chest pain)
Exercise time (min:sec)	8:01
Heart rate	99
Systolic blood pressure (mmHg)	180
Estimated METs	6.0				Ventilatory Efficiency
Oxygen uptake (ml/kg/min)	11.5	(62% predicted)		VE/VCO2 Slope	35.9
Oxygen uptake (ml/min)	1,215				OUES		1.48
VE (l/min)	41.6				PetCO2		31.7
VCO2 (ml/min)	1,470				Peak VE/VO2	34.4
O2 pulse (ml/beat)	12.3
RER	1.21		HRR1 = 10	Breathing reserve       23%
SaO2 (%)	95		HRR2 = 16
Perceived exertion	19

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 3-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 4 -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. 

_____________________________________________________________________________

             PeakVO2     Max Work     VO2@AT      Work@AT    VO2/Watts*     VO2/HR

            ml/kg/min       Watts          ml/kg/min        Watt       ml VO2/Watt  ml O2/beat _____________________________________________________________________________

Test-1       26.3             129                17.0                84                 11.5                11.0

              102%pred    94%pred                                                                         118%pred

Test-2        23.0             112                16.5                76                 13.1               10.0 

               94%pred     82%pred                                                                          113%pred

* Normal range: 8.7-11.9 ml/min/Watt

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 phosphorylation 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.