Continuing Education Activity
Cardiopulmonary fitness testing is a durable and versatile tool that provides valuable diagnostic and prognostic information regarding patients with cardiovascular and pulmonary disease. When combined with adjunctive imaging modalities, it provides additional information regarding the cardiac function and also helps in providing prognostic information. This activity reviews the importance of cardiopulmonary fitness testing and highlights the role of the cardiologists and healthcare team in managing patients who undergo this test.
- Describe the indications for cardiopulmonary fitness testing.
- Outline the key cardiopulmonary fitness testing variables and their clinical implications.
- Summarize the interpretation and reporting of cardiopulmonary fitness testing.
- Explain the importance of collaboration and communication amongst the interprofessional team to ensure the appropriate selection of candidates for cardiopulmonary fitness testing to enhance patient management.
Cardiopulmonary Exercise Testing (CPET) is a safe, non-invasive assessment of cardiorespiratory function. It allows the determination of crucial prognostic variables and can distinguish pathophysiology not apparent at rest. It can discriminate cardiovascular, ventilatory, and musculoskeletal limitations during exercise by monitoring disturbances in key variable responses such as: oxygen, carbon dioxide, minute ventilation, and heart rate.  It offers additional interpretive power over conventional stress testing and thus can lead to improved clinical decision-making and risk stratification in patients with cardiometabolic and respiratory disease.
The ability to perform physical exercise is dependent on the cardiovascular system's ability to deliver oxygen to the tissues, and eliminate the metabolic by-products produced. The transport of O2 and CO2 in and out of the human body is a sequential phenomenon. Three processes occur in the body that assists with the ability to supply O2 and remove CO2.
- External Respiration: Lung ventilation and gas exchange facilitate the delivery of O2 into the blood, and the elimination of metabolic by-products (CO2) produced by exercise.
- Circulation: Responsible for the transport of O2 and CO2.
- Internal Respiration: Mitochondria undergo oxidative phosphorylation in order to produce ATP, which in turn produces mechanical energy.
Ventilation-Perfusion Matching: In healthy individuals, exercise causes blood flow to the apex of the lung to increase, due to increased recruitment of previously unused capillaries (increase in tidal volume) along with decreased pulmonary vascular resistance. This results in increased flow to the pulmonary circuit during exercise with relatively small increases in pulmonary arterial pressure. The increase in tidal volume is seen early in exercise and is a contributing factor to increased minute ventilation. The ideal Ventilation (V) - Perfusion (Q) ratio to sustain exercise is ~1.0. Progressive exercise will ultimately end in a V/Q mismatch because cardiac output cannot keep up with the demand of the skeletal muscles. Certain disease states initiate the V/Q mismatch early, contributing to the exercise intolerance commonly observed. In patients with poor cardiac function, perfusion to the lungs is reduced, leading to a high V/Q ratio. Conversely, in patients with respiratory disease ventilation is impaired, causing a low V/Q ratio.
Per the AHA scientific statement for Cardiopulmonary Exercise Testing .
Class 1 indication:
- To evaluate exercise capacity and therapy response in patients with heart failure who are under consideration for heart transplantation
- Assessing exertional dyspnea of uncertain cause.
Class 2a indication:
- When subjective estimates like test time or work rate are unreliable, it helps evaluate exercise capacity for various medical reasons.
Class 2b indication:
- To evaluate response to an intervention where it is important to measure exercise tolerance as an endpoint.
- In cardiac rehabilitation to determine exercise training intensity.
Contraindications per AHA guidelines:
- Unstable Angina or recent myocardial infarction (within 2 days)
- Uncontrolled Cardiac Dysrhythmias associated with symptoms or hemodynamic compromise
- Symptomatic severe aortic stenosis or aortic dissection
- Uncontrolled heart failure
- Acute pulmonary embolus or infarction
- Acute myocarditis, pericarditis or endocarditis
- Acute systemic infection accompanied with symptoms
- Moderate valvular stenosis
- Hypertrophic cardiomyopathy
- Left main coronary artery stenosis
- Severe pulmonary or untreated severe systemic arterial hypertension
- High degree AV block
A metabolic cart is used to accurately measure the variables of metabolic gas exchange. To interpret the values accurately, adhering to the calibration standards and quality assurance procedures is essential. There may be slight differences in calibration techniques as there are a variety of metabolic carts available. Following the instructions provided by the manufacturer, in conjunction with the recommendation that is described in detail in the AHA scientific statement by Balady et al.  is vital.
Additionally, emergency equipment should be readily available. This includes:
- Crash Cart w/ cardioverter – defibrillator
- Ambu bag & mask appropriate for age
- Oxygen hook up
- IV start supplies
Choosing an appropriate exercise protocol is essential in increasing the validity of the results. Although there are multiple study protocols available for use, the clinician should tailor the protocol to the patient such that it can yield a fatigue-limited exercise in approximately 8 to 12 minutes. The most commonly used methodology is incremental or constant work protocols. Ramp protocols are a type of incremental protocol where there is a gradual increase in work rate at specified time intervals of each minute of different exercise phases.
Peak VO2: Maximal Oxygen Uptake
Maximal VO2 is the measure of one’s aerobic capacity representing the amount of oxygen taken in by the skeletal muscle during exercise. There is a linear relationship between exercise intensity and oxygen uptake until the cardiovascular system can no longer met the demands of the exercising muscle. This is known as an oxygen uptake plateau and achieved following progressive exercise.
VO2 is derived using the Fick equation where maximal oxygen uptake equals cardiac output x the arteriovenous difference (VO2 = CO x (CaO2 – CvO2). Higher VO2 values represent greater aerobic fitness. Men have higher peak VO2 due to increased levels of hemoglobin, increased stroke volume and greater muscle mass. 
Declines in VO2 happen with age, there is approximately a 10% decrease every ten years after 30 years of age. This is due to decreases noted in stroke volume and maximal heart rate.  Any pathophysiologic state can impair peak VO2 as seen in heart failure or chronic obstructive pulmonary disease (COPD) and even in deconditioning . Values below 80% of predicted (based on age, gender and anthropometric data) are considered abnormal. VO2 is the most important parameter, as it can quantitatively measure disease severity.
- VO2 < 80% predicted value represents reduced aerobic capacity, suggestive of cardiopulmonary or metabolic impairments.
- A low VO2 despite normal cardiovascular, pulmonary and metabolic parameters are suggestive of deconditioning.
O2 pulse is the amount of oxygen consumed by the tissues at any given heart rate (VO/HR). This value is used as a surrogate for stroke volume. Decreased O2 pulse often points to a cardiac limitation to exercise.
- <80% predicted is considered abnormal
There is a physiologic max for heart rate based on age. The generally accepted equation is: 220-age. The normal heart rate response to progressive exercise is linear. Peak exercise HR that is 20 bpm below (<85%) age-predicted max for subjects limited by volitional fatigue is considered chronotropic incompetence.
- Exaggerated HR response to exercise may be secondary to deconditioning
- Heart rate recovery: A slowed HRR is associated with poor prognosis
Exercise is a state of increased sympathetic tone which is overridden by local vaso-regulatory mechanisms. The metabolic byproducts produced by exercise all favor vaso-regulation which all lower systemic vascular resistance. Additionally, blood shunting occurs where any nonworking muscles/organs remain in a vaso-constricted state in order to promote more blood flow to the working muscles. The initial phase of progressive exercise CO is mainly increased due to the increased LV stroke volume in response to blood filling (frank-starling). Around 50% of the VO2 max, further increases in CO are augmented due to increased heart rate.
- There is a linear relationship between CO and oxygen uptake
- CO can increase up to 5x more than resting measurements during high intensity exercise.
Ventilatory Anaerobic Threshold (VAT)
VAT is the point in exercise where there is a supply /demand imbalance of oxygen being delivered to working muscles activating anaerobic metabolism. Minute ventilation increases disproportionately to the workload, where for any increases in VO2, VCO2 increases out of proportion. When a plot is drawn with VCO2 as X-axis and VO2 as Y-axis, the point at which the slope of VCO2/VO2 changes from less than 1 to more than 1 is the ventilatory threshold (V-slope method).  At this point in exercise, there are rising blood lactate levels and intracellular bicarbonate levels are not adequate to counteract cellular acidosis. As a compensatory measure, hyperventilation sets in, to dump off the excess VCO2 formed.
- Often occurs between 45-65% of VO2 max.
- <40% is considered abnormal
Ventilatory Efficiency (VE/VCO2)
The Ventilatory Efficiency slope is demonstrative of how hard a subject must breathe in order to eliminate CO2. It is the major link between the circulatory and ventilatory response to exercise. During exercise initiation, VE/VCO2 typically decreases due to improved ventilation perfusion matching. Throughout exercise, both minute ventilation and CO2 increase in order to maintain acid base status.
- Often measured at the VAT and can be used in submaximal tests
- Increased slope represents less efficient CO2 elimination
- Normal VE/VCO2 <35
- Often elevated in patients with heart failure, as their ventilation is higher for any given amount of CO2.
Respiratory Exchange Ratio: RER
Represents the metabolic exchange of gases in the tissues and is dependent on fuel utilization used for cellular metabolism. It is the ratio of CO2 elimination over O2 consumption. RER is mainly used as part of the criteria to measure a maximal effort.
- RER >1.1 indicates significant stress induced by exercise; however, not an indication to stop the test.
- If <1 in the absence of other hemodynamic abnormality or changes in the EKG, it either might be an indication for deconditioning with submaximal cardiovascular effort or severe COPD where the hyperinflation of lungs can interrupt the hyperventilation process needed to exhale the excess VCO2
Oxygen Uptake Efficiency Slope (OUES)
Slope of the logarithmic relationship between VO2 and minute Ventilation during exercise for any given VO2. The OUES is fairly linear throughout progressive exercise.
- Steeper slope represents more efficient oxygen uptake
- Known to be a significant predictor for mortality in adult heart failure patients
- Useful for submaximal testing
Etiologic Categorization of CPET parameters:
- Reduced VO2 max
- Reduced O2 pulse <80% predicted
- Evidence of chronotropic incompetence
- Evidence of ischemia
- Elevated VE/VCO2 slope
- Decreased Oxyhemoglobin saturations, <88% with exercise is clinically significant
- Abnormal spirometry/flow volume loops
- Peak exercise respiratory rate >50 per minute
- Reduced breathing reserve (lower than 20%)
- Elevated VE/VCO2 slope
- VAT achieved <40% of VO2 max
- Elevated lactate at any given level of submaximal work
- VE/VCO2 >50
Subject deconditioning is apparent from the following responses:
- Low VO2 measured in ml/kg/min (relative), despite normal VO2 measured in L/min (absolute)
- Low VO2 with the absence of other abnormal responses
- Low VAT
- Exaggerated Heart rate response
- Increased VO2/work slope
- indexed peak VO2 (mL/kg/min) less than predicted, absolute VO2 (L/min) normal or greater than predicted, oxygen indexed to lean body mass normal or greater than predicted
The most dangerous complications include: exercise-induced life-threatening arrhythmias (ventricular tachycardia, ventricular fibrillation, or marked bradycardia), orthopedic injury, hemodynamic instability, or acute myocardial infarction; all requiring immediate medical assessment and subsequent treatment. Other complications include arrhythmias like atrial fibrillation, supraventricular tachycardia, non-sustained ventricular tachycardia, syncope (including vasovagal syncope), stroke, or transient ischemic attack.
Multiple health conditions can contribute to exercise intolerance in both healthy and unhealthy people with various known and unknown comorbidities; cardiopulmonary fitness testing helps in establishing the etiology and also gives prognostic importance, thus playing a significant role in alleviating the diagnostic challenge for clinicians.  When combined with the standard tools of clinical investigation, the cardiopulmonary exercise test is the “gold standard” method for objectively assessing cardiorespiratory physiology.
Enhancing Healthcare Team Outcomes
Cardiopulmonary fitness testing requires an interprofessional team effort, including exercise physiologists, physician assistants, nurses, physical therapists under the supervision of a cardiologist. When a patient is considered high risk for testing (example: in patients within seven days of myocardial ischemia, patients with malignant arrhythmia, severe pulmonary arterial hypertension), the recommendation is that direct supervision of the procedure and immediate availability of a cardiologist is needed to improve patient safety.
We thank Ms. Angela Romme, MS for her insightful comments.