Preface
People are usually breathless when they are doing something, so it makes sense to assess their symptoms and make physiological measurements during exercise rather than to rely on investigations performed at rest. Cardiopulmonary exercise testing is therefore an excellent way to work out why someone is breathless and to quantify their limitation.
Maximum oxygen uptake (VO2max) during exercise is also one of the best predictors of operative mortality and of prognosis in chronic cardiac or respiratory disease (as well as being an excellent measure of overall fitness in athletes). The cardiopulmonary exercise test (CPET), during which VO2max is routinely measured, is an increasingly common component of preoperative assessment and the management of patients with chronic lung or heart problems.
This book is a guide for clinicians and works logically through the main parameters that are measured during a CPET. The physiology behind the calculation of these parameters is explained, so that interpretation of the results is based on a full understanding of the scientific principles from which they are derived. Clinical scenarios, key points, and practical tips all make this book easy to follow.
The first section of the book discusses the indications for a CPET, the phases of the test, and how it should be supervised.
The second section analyses key CPET parameters: five primary measurements—oxygen uptake, heart rate, ventilation, carbon dioxide output, and peripheral oxygen saturation (SpO2); three derived indices—oxygen (O2) pulse, the respiratory exchange ratio, and ventilatory equivalents; and two thresholds—the anaerobic threshold and the respiratory compensation point.
The third section discusses how to integrate the results of a CPET into a clinical report to help the referring clinician, with advice on the prescription of exercise.
Little prior knowledge of the subject is assumed, but by the end of the book, the reader will know what is going on in each of the plots of a standard nine-panel CPET display. They will be able to look at this display and decide what is limiting exercise.
This new edition has been extensively expanded and updated, with many new sections and figures, reflecting the accumulation of evidence in the field of CPET. The focus remains on interpretation, but in response to requests from readers of the first edition, the sections on supervision of a CPET have been expanded, with further detail on respiratory measurements and some sample exam questions.
William J.M. Kinnear James H. Hull
List of practical tips 153
Example exam questions 159
Glossary 211
Bibliography 213
Index 215
Abbreviations
ACSM American College of Sports Medicine
AT anaerobic threshold
Bf breathing frequency
BMI body mass index
BNP brain natriuretic peptide
BP blood pressure
bpm beats per minute
CaO2 oxygen content of arterial blood
CIH chronic idiopathic hyperventilation
CK creatine kinase
CLE continuous laryngoscopy during exercise
cm centimetre
CO cardiac output
CO2 carbon dioxide
COPD chronic obstructive pulmonary disease
CPET cardiopulmonary exercise test
CT computerized tomography
CvO2 oxygen content of mixed venous blood
DASI Duke Activity Status Index
dl decilitre
ECG electrocardiogram
EIAH exercise-induced arterial hypoxaemia
EIB exercise-induced bronchoconstriction
EILO exercise-induced laryngeal obstruction
EOV exercise oscillatory ventilation
etCO2 end-tidal carbon dioxide
etO2 end-tidal oxygen
FEV1 forced expiratory volume in one second
FTP functional threshold power
FVC forced vital capacity
g gram
H+ hydrogen ion
Hb haemoglobin
HCM hypertrophic cardiomyopathy
HCO3– bicarbonate
H2O water
HR heart rate
HRR heart rate reserve
IBW ideal body weight
IC inspiratory capacity
I/E inspiratory/expiratory
ILD interstitial lung disease
ITU intensive therapy unit
kcal kilocalorie
kg kilogram
kPa kilopascal
l litre
m metre
μM micromole per litre
MAP mean arterial pressure
MET metabolic equivalent; expressing work done as a multiple of resting energy expenditure
MFVL maximal flow–volume loop
min minute
ml millilitre
mm millimetre
mmHg millimetre of mercury
mmol millimole
ms millisecond
MVV maximum voluntary ventilation
NT-pro-BNP N-terminal pro-B-type natriuretic peptide
NYHA New York Heart Association
O2 oxygen
O2 pulse oxygen pulse
OUES oxygen uptake efficiency slope
PaCO2 arterial carbon dioxide partial pressure
PACO2 alveolar carbon dioxide partial pressure
PaO2 arterial oxygen partial pressure
PAR Q Physical Activity Readiness Questionnaire
PEFR peak expiratory flow rate
PetCO2 end-tidal carbon dioxide partial pressure
PFO patent foramen ovale
PO2 oxygen partial pressure
PoTS postural tachycardia syndrome
PvCO2 mixed venous carbon dioxide partial pressure
PvO2 mixed venous oxygen partial pressure
PVR peripheral vascular resistance
Q lung perfusion
RCP respiratory compensation point
RER respiratory exchange ratio
RPE Rating of Perceived Exertion (scale)
rpm revolution per minute
RQ respiratory quotient
s second
SATET sub-anaerobic threshold exercise test
SCE Specialty Certification Examination
SHIP Study of Health in Pomerania
SpO2 peripheral oxygen saturation
SV stroke volume
Te expiratory time
Ti inspiratory time
V lung ventilation
VCO2 carbon dioxide output
Vd dead space volume
VE minute ventilation
VEmax maximum minute ventilation
Veq ventilatory equivalents
VeqCO2 ventilatory equivalents for carbon dioxide
VeqO2 ventilatory equivalents for oxygen
VO2 oxygen uptake
VO2max maximum oxygen uptake
Vt tidal volume
W watt
WR work rate
SECTION 1 Introduction
Why do a cardiopulmonary exercise test?
Key points
• A cardiopulmonary exercise test (CPET) involves measurements of cardiac and respiratory function whilst the subject exercises up to their maximum capacity.
• A CPET can be a useful tool for diagnosing heart and lung disease, working out why someone is breathless, quantifying fitness, and predicting outcomes.
• Preoperative CPET testing allows stratification of surgical risk and planning post-operative care.
1.1 What is a CPET?
In a cardiac exercise test, a patient with known or suspected coronary artery disease exercises on a treadmill whilst their electrocardiogram (ECG) is primarily monitored for ST segment changes. ‘Cardiopulmonary’ exercise tests go a step further by attaching a mask (or mouthpiece) to record breathing. This gives lots more information, not just about the lungs and heart, but also about the circulation and leg muscles. It also enables an estimation of work capacity and overall motivation to perform exercise.
1.2 Key measurements
A CPET generates many numbers and graphs, but most of the useful information is derived from the four measurements described in Box 1.1.
Box 1.1 Key CPET measurements
• The volume of air breathed in and out (minute ventilation, or VE)
• The volume of oxygen (O2) used up by the body (oxygen uptake, or VO2)
• The volume of carbon dioxide (CO2) produced (carbon dioxide output, or VCO2)
• Heart rate (HR)
Three more indices can be derived by combining two of these measurements: the respiratory exchange ratio (RER), oxygen (O2) pulse, and ventilatory equivalents (Veq). These parameters are also used to obtain a couple of useful thresholds: the anaerobic threshold (AT) and respiratory compensation point (RCP). So CPET interpretation, at an introductory level, only requires an understanding of fewer than ten parameters.
Learning point
Most of the information we gain from a CPET is derived from just four key measurements and their relationship during incremental exercise (Box 1.1).
1.3 Why do a CPET?
Most patients with cardiac or respiratory problems have symptoms which are worse on exertion, whereas many diagnostic tests are performed with a patient sitting in a chair or lying on a couch. It makes much more sense to undertake some physiological measurements when someone is doing an activity. A CPET puts the cardiac and respiratory systems under stress, so that the capacity and reserve of the body can be assessed, particularly in terms of its ability to deliver O2 to the exercising muscles (Box 1.2).
Practical tip
It is seldom of value to refer a patient for a CPET if they have an obvious impediment to exercise, e.g. a patient with chronic pain or musculoskeletal impairment
1.4 Things to do before you consider a CPET
Prior to a diagnostic CPET, a detailed history and clinical examination are mandatory. A few basic tests, such as a chest X-ray, ECG, haemoglobin (Hb) concentration, and renal function, should have been performed, and also arterial blood
Box 1.2 Reasons for doing a CPET
CPET is a useful tool for:
• Finding out what is wrong with a patient who is short of breath on exertion
• Assessing the contribution of cardiac or respiratory pathologies to incapacity
• Quantifying the extent of any impairment and thus the prognosis
• Assessing the risk to the patient of any potential surgical procedure
• Measuring the response to any intervention
gases if there is any clinical suspicion of respiratory failure or a low resting peripheral O2 saturation (SpO2).
Most patients will have had spirometry and a flow–volume loop prior to a CPET. More detailed tests will often have been performed, depending upon local practice, availability, and the clinical indication for the test. Usually, static lung volumes and carbon monoxide transfer factor will be measured, and often an ECG and other cardiac investigation if there is any clinical suspicion of heart failure.
Practical tip
A careful clinical assessment and a few simple tests beforehand will make interpretation of a CPET very much easier.
These preliminaries are important. Whilst it may be possible to infer from CPET results that the patient might be anaemic or have renal failure, intermittent claudication, or a muscle disease, there are other (better) ways of working this out. Overall, a CPET rarely gives a definitive diagnosis and usually only helps direct clinicians towards a possible group of clinical conditions (e.g. conditions causing ventilatory limitation or cardiac impairment). Like any test, a CPET is probably best viewed in a ‘Bayesian diagnostic model’, helping to alter or enhance the pre- to post-test probability or increase the likelihood of a given diagnosis, i.e. if you suspect a problem, then a CPET can help confirm or refute your suspicions.
1.5 Things that are not covered in this book
This book focuses primarily on how to supervise a safe CPET and on providing a basic set of rules to help you interpret the various measurements obtained. Other ways of assessing exercise capacity—such as corridor or shuttle walks— will not be discussed, although clearly the physiological principles are equally applicable to the interpretation of these more simple tests.
Likewise, the technical aspects of a CPET (how the analysers work, calibration, setting up the equipment, working out the ramp rate, and so on) will not be discussed in any detail. This book is mainly about how to interpret the results. Measurements that involve insertion of central venous catheters, arterial lines, or blood sampling are beyond the scope of this text. Similarly, tests where the subject inhales supplementary O2 (or indeed air with an artificially low O2 content) are more complicated to interpret and are beyond the scope of this introductory textbook.
Further reading
Albouaini K et al. Cardiopulmonary exercise testing and its application. Heart. 2007 Oct;93(10):1285–92.
Arena R and Sietsema K. Cardiopulmonary exercise testing in the clinical evaluation of patients with heart and lung disease. Circulation. 2011 Feb;123(6):668–80.
Balady GJ et al. Clinician’s guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010 Jul;122(2):191–225.
Guazzi M et al. Focused update: clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation. 2016 May;133(24):e694–711.
Parshall MB et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012 Feb;185(4):435–52.
Parasuraman S et al. Healthcare professional’s guide to cardiopulmonary exercise testing. Br J Cardiol. 2015 Dec;22:156.
Palange P et al. Recommendations on the use of exercise testing in clinical practice. Eur Respir J. 2007 Jan;29(1):185–209.
Pratter MR et al. An algorithmic approach to dyspnea. Respir Med. 2011 Jul;105(7):1014–21.
Pre-test assessment
Key points
• CPET is a very safe test.
• Several conditions increase the potential risk of a CPET.
• A pre-test ECG should be looked at carefully for conditions which predispose to cardiac events.
• The indication for a CPET must be clearly defined.
The process of a CPET can be broken down into four steps (Box 2.1). We have already looked at the first step in the previous chapter. Most of the rest of the book is about the fourth step—how to use the results. You may be itching to get your teeth into the interpretation of CPET data, but first we need to assess our patient carefully. In the two following chapters, we will cover exactly how to do the test and make sure we do it as safely as possible. Then it will be time to look at the data.
2.1 Safety and the pre-test assessment
CPET is a safe test; in one series of 70,000 tests, no deaths occurred and only six major complications were encountered (Box 2.2).
Box 2.1 Steps in the CPET process
• The clinical decision to undertake a CPET
• Pre-test assessment
• The CPET itself
• Interpretation of the results
Box 2.2 Risks of CPET
• Myocardial infarction
• Arrhythmia
• Haemodynamic instability
• Bronchospasm
• Hypoglycaemia
• Musculoskeletal injury
• Hyperventilation ± syncope
This acknowledged, it is still vital that before any CPET, contraindications are checked and patient safety is prioritized. A pre-participation medical screening questionnaire, such as the Physical Activity Readiness Questionnaire (PAR Q), can be used to screen for problems, but ultimately the decision to proceed with a test is at the discretion of the supervising/responsible clinician. We need to be aware of the risks involved and the side effects or problems that can occur. In our experience, the most common adverse events that occur are dizziness and collapse, arising from hyperventilation or vasovagal reactions if blood sampling is undertaken. Contra-indications to CPET commonly cited are listed in Box 2.3.
2.2 The day of the test
Before starting the test, we must double-check the indication and check the risks (Box 2.4).
We will come back to the pre-test ECG shortly. If there is any possibility of exercise-induced asthma, check the forced expiratory volume in one second
Box 2.3 Contraindications to CPET
• History of exercise syncope or pre-syncope
• Mental impairment, with inability to co-operate with test procedure
• Musculoskeletal problem limiting exercise capacity
• Acute coronary syndrome/myocardial infarction within last seven days
• Unstable angina
• Poorly controlled New York Heart Association (NYHA) class III or IV heart failure
• Symptomatic severe aortic stenosis
• Uncontrolled arrhythmia with haemodynamic compromise
• Aortic dissection
• Aortic aneurysm
• Acute asthma/exacerbation of COPD
• Pulmonary oedema
• Respiratory failure [arterial O2 partial pressure (PaO2) <8 kPa]
• Severe pulmonary hypertension
• Acute pulmonary embolism
• Recent deep vein thrombosis
• Pulmonary arterial hypertension
• Frailty
• History of syncope/seizures
Box 2.4 Things to consider before starting a CPET
• What is the reason the CPET is being performed?
• Is this reason still relevant to the patient?
• What are the risks in this particular patient?
• Does the potential gain in clinical information justify the risk?
• Is the resting ECG normal?
• What are the criteria for stopping the test in this patient?
• Is everyone involved clear about their role?
• Is the emergency equipment in working order and readily accessible?
• Is there O2 to hand (and is the cylinder full if there is no piped source)?
• Do you need a bag of carbon dioxide (CO2) ready if there is a chance of hyperventilation?
• If the patient uses an inhaler, where is it?
• Is there a nebulizer and a supply of beta-agonist available?
• Where would we get intravenous fluids and giving sets, etc. if we needed them?
(FEV1) and make sure that a subject’s asthma is no worse than when the test was requested; it would be inappropriate to proceed with the test during an exacerbation or acute illness; there is also a risk that strenuous exercise undertaken during a viral illness can lead to cardiac damage. Moreover, if the result shows an abnormal result, then it is actually very difficult to interpret the findings. If the patient has waited ages for the CPET appointment, you may be persuaded or tempted to proceed, even though they have a ‘cold’. It is, however, important that you re-schedule the test.
Practical tip
If a patient is prescribed a regular medication, then there will often be a question as to whether this medication should be taken on the day of testing. Generally speaking, patients should be advised to take all of their usual medications—this is especially true if a patient is developing symptoms despite the use of medications (e.g. for asthma). Certain drugs will impact subsequent interpretation (e.g. beta-blockers), but providing they are listed and known, this is not a problem. Moreover, discontinuing cardiac medications suddenly can increase the risk of an adverse event during the test
2.3 The pre-test resting ECG
An ECG should be performed on the day of the CPET. This gives us a baseline with which to compare during the test, but it also alerts us to the presence of
an increased risk of adverse events on exercise. Always look for conditions such as hypertrophic cardiomyopathy (HCM) (see Chapter 18) or the long-QT syndromes which can predispose to adverse cardiac events (Box 2.5).
If there are ECG abnormalities indicative of myocardial ischaemia, get hold of previous ECGs just to be sure there has not been an acute coronary event since the referral for the CPET was made. Remember that T wave inversion is almost always seen in lead aVr, and it can also be seen in normal subjects in leads III, V1, and V2. T wave inversion beyond these leads requires an explanation.
Occasionally you will pick something up on the pre-test ECG which has not been noticed previously and may well explain a patient’s symptoms. For example, the pre-test ECG may be the first occasion on which atrial fibrillation has been documented. Do not proceed with the test until you have talked to the referring clinician and/or are fully competent to make this decision, particularly if there is an increased risk of adverse events.
Other occasions when you might proceed with an exercise test in the presence of an ‘abnormal’ ECG is in black Africans, where ST elevation, especially in the anterior leads, is a normal variant. Look very carefully at the rest of the ECG, particularly for Brugada syndrome (Box 2.6).
There will be occasions when you undertake a CPET in the presence of an abnormal resting ECG (e.g. in the preoperative assessment of valvular disease), but proceed with caution. Likewise if there are clinical features raising the possibility of HCM, then do not proceed, unless, of course, the diagnosis is already known and the test is part of HCM assessment.
• Ventricular ectopics (especially if frequent and multifocal, i.e. with varying morphology)
• Atrio-ventricular block
• Short PR interval
• Delta wave
• Widened QRS
• Axis deviation
• Ventricular hypertrophy*
• Corrected QT interval longer than 500 ms
• ST elevation >1 mm
• ST depression
• T wave inversion (except in leads III, aVr, and V1)
* On voltage criteria, this may be seen in trained athletes who may also have a partial right bundle branch block and/or a first-degree atrio-ventricular block.
Box 2.5 Pre-test ECG abnormalities indicating higher risk of adverse events during a CPET
Box 2.6 ST changes of relevance to CPET testing
ST depression
• Myocardial ischaemia
• Hypertrophic cardiomyopathy*
• Digitalis
ST elevation
• Myocardial infarction
• Normal in black Africans (V2–V4)
• Hyperventilation
• Brugada syndrome (coved ST elevation in V1 and V2)*
• Some highly trained athletic individuals (V2–4)*
* Discuss with a specialist sports cardiologist.
Practical tip
Hyperventilation can cause ST segment and T wave changes; these changes can thus develop if a subject hyperventilates during a CPET. Check the ventilatory pattern, RER, and end-tidal CO2 (etCO2) for clues, but only consider this as the explanation if there is an absence of other cardiac risk factors, symptoms, or other pointers to an underlying cardiac cause.
2.4 Diet, exercise, and clothing
Individuals undertaking CPET need to be counselled beforehand regarding the nature of the test and the need to wear appropriate clothing (i.e. not tight-fitting and with appropriate footwear). Light dietary intake is recommended pre-testing, and not within 30 minutes of the test; high fat or sugar content intake pre-test can impact the resting RER value (see Chapter 10). Caffeine and alcohol should not be ingested on the day of the CPET. Likewise no strenuous exercise should be taken beforehand on the day of the test.
Further reading
Levett DZH et al. Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation. Br J Anaesth. 2018 Mar;120(3):484–500.
Magri D and Santolamazza C. Cardiopulmonary exercise test in hypertrophic cardiomyopathy. Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S102–9.
Radtke T et al. ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases. Eur Respir Rev. 2019 Dec;28(154):180101.
