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Cardiopulmonary Exercise Testing: Basics of Methodology

and Measurements
Alessandro Mezzani
Exercise Pathophysiology Laboratory, Cardiac Rehabilitation Division, Istituti Clinici Scientifici Maugeri Spa Società Benefit, Scientific
Institute of Veruno, Istituto di Ricovero e Cura a Carattere Scientifico, Veruno, Novara, Italy
ORCID ID: 0000-0003-1595-6227 (A.M.).

Abstract relevant in the clinical setting. The choice of parameters to be

considered will depend on the indication to cardiopulmonary
Cardiopulmonary exercise testing adds measurement of ventilation exercise testing in the individual subject or patient, namely, exercise
and volume of oxygen uptake and exhaled carbon dioxide to routine tolerance assessment, prognostic stratification, training prescription,
physiological and performance parameters obtainable from treatment efficacy evaluation, diagnosis of causes of unexplained
conventional exercise testing, furnishing an all-around vision of the exercise tolerance reduction, or exercise (patho)physiology evaluation
systems involved in both oxygen transport from air to mitochondria for research purposes. Overall, cardiopulmonary exercise testing is a
and its use during exercise. Peculiarities of cardiopulmonary exercise methodology now widely available and supported by sound scientific
testing methodology are the use of ramp protocols and calibration evidence. Despite this, its potential still remains largely underused.
procedures for flow meters and gas analyzers. Among the several Strong efforts and future investigations are needed to address these
parameters provided by this technique, peak oxygen uptake, first and issues and further promote the use of cardiopulmonary exercise testing
second ventilatory thresholds, respiratory exchange ratio, oxygen in the clinical and research setting.
pulse, slope of ventilation divided by exhaled carbon dioxide
relationship, exercise oscillatory ventilation, circulatory power, and Keywords: exercise; gas exchanges; ventilation; oxygen uptake;
partial pressure of end-tidal carbon dioxide are among the most exhaled carbon dioxide

(Received in original form December 15, 2017; accepted in final form May 15, 2017 )
Correspondence and requests for reprints should be addressed to Alessandro Mezzani, M.D., Exercise Pathophysiology Laboratory, Cardiac Rehabilitation
Division, Istituti Clinici Scientifici Maugeri Spa SB - Scientific Institute of Veruno IRCCS, Via per Revislate, 13, 28010 Veruno (NO), Italy. E-mail: alessandro.
[email protected]
Ann Am Thorac Soc Vol 14, Supplement 1, pp S3–S11, Jul 2017
Copyright © 2017 by the American Thoracic Society
DOI: 10.1513/AnnalsATS.201612-997FR
Internet address: www.atsjournals.org

Cardiopulmonary exercise testing joins clinical settings, and cardiopulmonary Methodology

ventilation and volume of oxygen uptake exercise testing indications entail
(V_ O2) and exhaled carbon dioxide (V_ CO2) to functional capacity assessment, prognostic Ventilation parameters and respiratory
routine physiological and performance stratification, training prescription, treatment gases can be collected using a face mask or a
parameters measured during incremental efficacy evaluation, diagnosis of causes of mouthpiece, with the choice between the
exercise testing, such as heart rate, blood unexplained reduced exercise tolerance, two more linked to a given laboratory’s
pressure, work rate, and exercise duration. and exercise pathophysiology evaluation in habits than to specific advantages. A face
Therefore, this methodology markedly an extremely wide spectrum of clinical mask allows patient swallowing, which a
increases the amount of information pictures (1–7). The basic parameters mouthpiece does not. On the other hand,
obtainable from conventional exercise peculiar to cardiopulmonary exercise some patients may feel uncomfortable
testing, furnishing an all-around vision of the testing (i.e., ventilation and V_ O2 and V_ CO2) using a face mask because of lack of air
systems involved in both O2 transport from are now routinely obtainable in spreadsheet sense. In any case, every laboratory should
air to mitochondria and its use during format by all commercially available give patients a choice between a face mask
exercise. Gas exchange measurements during systems, providing an easy-to-use platform and a mouthpiece, according to their
exercise have been demonstrated to enhance for straightforward data processing and preferences. Cardiopulmonary exercise tests
the decision-making process in several interpretation. can be performed using incremental or

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160

140 Ramp 30 W/2 min

15 W/min
120

100
W

80
Ramp 20 W/2 min
60 10 W/min

40

20

0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
Time (min) Time (min)

Figure 1. Ramp incremental (left panel) and 2-minute incremental (right panel) protocols for cycle ergometry. Red dashed lines represent protocols
reaching an equal work rate of 150 W after 10 minutes of exercise; blue solid lines represent protocols reaching an equal work rate of 100 W after 10
minutes of exercise. The work rate increment is added at the start of each 2-minute stage for the conventional incremental test, whereas the
increment is equal to 1 W every 6 seconds and 1.5 W every 6 seconds for the 10 W/min and 15 W/min ramp protocols, respectively, beginning from Time
0 of the exercise period.

constant work rate protocols, according to and more readable for the operators. calibrated immediately before each test,
work rate progressive increase or constancy Cardiopulmonary exercise tests can be and the test should not be performed if
during the test, respectively. Incremental performed on different kinds of proper calibration is not confirmed.
tests are aimed at maximally stressing the ergometers (i.e., cycle ergometer or Response times of the analyzers and
O2 transport and use system and are treadmill), the pros and cons of which are transport delay between sampling point
routinely used in the clinical setting, summarized in Table 1. Of note, ramp and analyzers must be systematically
whereas constant work rate tests are usually incremental protocols are much easier to checked as well. In addition, because
performed at submaximal effort intensities implement when a cycle ergometer is used. ambient conditions affect the concentration
and mainly used for research purposes. Cardiopulmonary exercise testing of oxygen in the inspired air, temperature,
Among incremental protocols, the ramp- systems contain flow meters and gas barometric pressure, and humidity
like ones are preferred to conventional analyzers that allow for breath-by-breath should also be taken into account.
incremental tests whenever possible measurement of ventilation and the V_ O2 Calibration procedures are automatically
(Figure 1). Ramp protocols are and V_ CO2. As flow meters and gas analyzers performed by all commercial
characterized by a gradual increase of work are prone to drift, all systems should be cardiopulmonary exercise testing software.
rate, evenly distributed within each minute
of the exercise phase (8). For example, on a
cycle ergometer, a 10-W/min ramp
Table 1. Use of treadmill versus cycle ergometer for cardiopulmonary exercise testing
protocol (which is frequently used in the
clinical setting) increases the work rate by
1 W every 6 seconds. Treadmill Cycle
Ergometer
Several ramp grades are commonly
used for patients, with 5 W/min, 7 W/min,
10 W/min, and 15 W/min the most popular. Higher peak oxygen uptake X
Easier implementation of ramp protocols X
The choice of ramp protocol steepness Possibility to quantify external work X
should be tailored to the subject’s exercise Higher ECG quality X
tolerance, aiming at a test duration ranging Possibility to obtain blood specimens during exercise X
between 8 and 12 minutes. The advantage Higher safety X
of ramp protocols is twofold: first, the work Possible use in supine position X
Smaller size X
rate increase is devoid of brisk step increases Less noisy X
typical of step protocols (e.g., 25 W every 3 Lower cost X
minutes); second, the trend of parameters Ease of movement X
changes over time is not affected by protocol Greater experience in Europe X
Greater experience in the United States X
steps, making physiological responses linear

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Peak V_ O2 V_ O2Peak declines on average by 10% and so forth but also in bed-rest
per decade after the age of 30, due to deconditioning (15).
V_ O2 is measured in liters or milliliters of decreasing maximal heart rate, stroke Of note, C(a–v)O2 increases linearly
oxygen per minute or in milliliters per volume, blood flow to skeletal muscle, and with work rate progression during
kilogram of body weight per minute and is skeletal muscle aerobic potential with incremental exercise, and its value is
defined by the Fick principle: V_ O2 equals decreasing age (9) (Table 2). In addition, relatively fixed at peak effort in both
cardiac output (CO) 3 C(a–v)O2, where V_ O2Peak is 10 to 20% greater in men than in normal subjects and patients. Accordingly,
C(a–v)O2 is the arteriovenous oxygen content women of comparable age (10), because peak CO is indirectly determinable
difference (5). Peak oxygen uptake (V_ O2Peak) of higher hemoglobin concentration and according to the Fick principle (see above)
greater muscle mass and stroke volume in using estimated peak C(a–v)O2 and
is a parameter describing the maximal
measured V_ O2Peak (16).
amount of energy obtainable by aerobic men (Table 2).
metabolism per unit of time (aerobic power) All pathophysiological states impairing
at peak incremental exercise and is defined oxygen transport from air to mitochondria
Ventilatory Thresholds
as the highest volume of V_ O2, averaged and its use during exercise will determine
over a 20- to 30-second period, achieved some degree of reduction of V_ O2Peak with
During incremental exercise, an energy
at presumed maximal effort during an respect to predicted values according to age requirement is reached above which
incremental cardiopulmonary exercise test. and sex. This is commonly observed not anaerobic metabolism is activated, with
V_ O2Peak is known to describe patient exercise only in several different organ and system blood lactate concentration increasing
tolerance far more reliably than performance diseases, such as chronic heart failure above baseline level at a progressively
descriptors obtainable by conventional (11), chronic obstructive pulmonary steeper rate (2, 5, 17, 18). Almost all
exercise testing, such as exercise duration disease (12), amyotrophic lateral sclerosis hydrogen ions generated in the cell from
or peak work rate (1). (13), mitochondrial myopathies (14), lactic acid dissociation are buffered by

Table 2. Normal values

Parameters Normal Values Formulae

V_ O2Peak, ml/min Age (yr) M* W* Sedentary men:†

20–29 3,250–2,970 2,000–1,840 [50.72 2 (0.372 3 age)] 3 weight
30–39 2,950–2,690 1,820–1,660
40–49 2,670–2,400 1,640–1,490 Sedentary women:†
50–59 2,380–2,130 1,470–1,320 [22.78 2 (0.17 3 age)] 3 (weight 1 43)
60–69 2,110–1,840 1,300–1,140
70–80 1,820–1,570 1,120–940
1stVT oxygen uptake .40% predicted V_ O2Peak —
40–60% measured V_ O2Peak
Peak oxygen pulse, ml/beat M* W* Predicted V_ O2Peak/predicted peak
20–29 16.2–15.6 10.0–9.6 heart rate
30–39 15.5–14.9 9.6–9.2
40–49 14.8–14.1 9.1–8.7
50–59 14.0–13.2 8.6–8.2
60–69 13.1–12.2 8.1–7.5
70–80 12.1–11.1 7.4–6.7
V_ E/V_ CO2 slope M W Sedentary men:‡ 0.12 3 age 1 21
20–39 23.4–25.7 26.8–28.3 Sedentary women:‡ 0.08 3 age 1 25.2
40–59 25.8–28.1 28.4–29.9
60–80 28.2–30.6 30.0–31.6
Peak circulatory power, Mx Fx —
ml/kg/min 3 mm Hg 20–39 8,600–7,000 6,660–5,600
40–59 7,050–5,680 5,480–4,400
60–80 5,630–4,200 4,320–3,140
1stVT partial pressure of end-tidal 3- to 8-mm Hg increase with respect to resting value —
carbon dioxide, mm Hg

Definition of abbreviations: 1stVT = first ventilatory threshold; M = men; V_ CO2 = volume of exhaled carbon dioxide; V_ E = ventilation; V_ O2Peak = peak oxygen
uptake; W = women.
*Values are calculated for men of 75 kg and women of 60 kg weight.
†
Formulae for normal-weight subjects according to Reference 20, which also reports formulae for under- and overweight subjects.
‡
Formulae for normal subjects according to Reference 20.
x
Values are calculated for men of 75 kg and women of 60 kg weight, using V_ O2Peak values reported above and a peak systolic blood pressure value of
200 mm Hg.

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bicarbonate, yielding an excess carbon greater than 1 (Figure 2, upper panel), ventilatory threshold or “respiratory
dioxide amount that makes the V_ CO2 versus occurring in the vast majority of subjects compensation point” (Figure 2, lower
V_ O2 relationship become steeper. By and patients between 40 and 60% of panel) (18) and is usually attained at
measuring at the mouth gas exchange V_ O2Peak (20). around 70 to 80% of V_ O2Peak.
modifications induced by these metabolic With increasing exercise intensity The first and second ventilatory
changes, the so-called first ventilatory above the first ventilatory threshold, a point threshold are important parameters for
threshold can be identified by analyzing the in time is reached when intracellular aerobic training intensity prescription over a
slope of V_ CO2/V_ O2 relationship (plotted on bicarbonates are no longer able to wide spectrum of exercise capacities,
equal scales) during ramp incremental adequately counteract exercise-induced ranging from top-level athletes to patients
exercise (19). Accordingly, the first metabolic acidosis. Hyperventilation thus with severely reduced exercise performance
ventilatory threshold is the point of develops through a ventilation increase in (21). As a multitude of different (and
transition of the slope from less than 1 to excess of V_ CO2, which is termed the second somewhat confusing) terms are found in
the literature describing the two thresholds,
the term “ventilatory” thresholds is
1stVT preferred (22). This is because those two
1.5
transitions are detected using incremental
exercise-induced changes in ventilation-
related parameters and not in direct
1.0
descriptors of metabolic homeostasis
VCO2 (L/min)

alteration (e.g., lactic acid).

Finally, ventilatory thresholds are not
always clearly identifiable in patients with
0.5 severely reduced exercise tolerance, and
inability to identify the first ventilatory
threshold plays an important negative
prognostic role in patients with advanced
0 chronic heart failure (23).
0 0.5 1.0 1.5
VO2 (L/min)
Respiratory Exchange Ratio
1stVT 2ndVT
50 The respiratory exchange ratio is the ratio
between V_ CO2 and V_ O2. As discussed above,
with increasing exercise intensity, lactic
acid buffering generates an excess V_ CO2,
40 which increases the respiratory exchange
= VE/VCO2

ratio numerator at a faster rate than the

= VE/VO2

denominator. Therefore, a respiratory

= [Lactate] (mmol/L)

8 exchange ratio higher than 1.00 implies

30 significant anaerobic metabolism activation
6
above the first ventilatory threshold and is
4 further increased by hyperventilation
occurring past the second ventilatory
20 2 threshold. This physiological response to
0 0 exercise is consistent across healthy
0 25 50 75 100 subject and patient populations, which
WR (W) makes peak respiratory exchange ratio an
objective descriptor of maximal effort
Figure 2. (Upper panel) Volume of exhaled carbon dioxide (V_ CO2) as a function of volume of oxygen attainment and subject motivation
uptake (V_ O2) during incremental exercise. The point in time when the V_ CO2/V_ O2 slope increases its (Table 3) (i.e., of a crucial issue to guarantee
steepness due to excess V_ CO2 from lactic acid buffering is the first ventilatory threshold. The initial and reliable and clinically meaningful
final phases of exercise (blue rectangles) are usually excluded from the analysis due to possible V_ O2Peak values) (24).
hyperventilation during these periods. (Lower panel) Ventilatory equivalents for oxygen and carbon Of note, even though a peak respiratory
dioxide as a function of work rate (WR) during ramp incremental exercise. The nadir of the ventilatory
exchange ratio of higher than 1.10 is
equivalent for oxygen (V_ E/V_ O2) identifies the first ventilatory threshold (i.e., the point in time when
ventilatory drive starts increasing relative to V_ O2 due to excess V_ CO2 from anaerobic metabolism generally considered to describe a significant
activation). The nadir of ventilatory equivalent for carbon dioxide (V_ E/V_ CO2) identifies the second exercise-induced whole-body stress, it
ventilatory threshold, namely, the point in time when ventilatory drive starts increasing relative to V_ CO2 must not be considered an indication for
(i.e., when hyperventilation occurs). V_ E = ventilation; 1stVT = first ventilatory threshold; 2ndVT = test interruption. On the other hand,
second ventilatory threshold. achievement of a peak respiratory exchange

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Table 3. Criteria of maximal effort by C(a–v)O2). Assuming normal values of Ventilation and Slope of the
attainment arterial oxygen content and C(a–v)O2 at Ventilation/V_ CO2 Relationship
peak effort, peak stroke volume in
Failure of oxygen uptake and/or heart rate to milliliters can then be estimated as (oxygen From a physiological standpoint, ventilation
increase with further increase in work rate pulse/15) 3 100, where oxygen pulse is in is equal to 863 3 V_ CO2/[PaCO2 3 (1 2 VD/
Peak respiratory exchange ratio > 1.10–1.15 milliliters per beat (5). However, this VT)], where V_ CO2 is the volume of exhaled
Post-exercise blood lactate estimation must be used with caution.
concentration > 8 mmol/dl carbon dioxide, PaCO2 is the partial pressure
Rating of perceived exertion > 8 (on the The subjects must be normal and motivated of arterial carbon dioxide, and VD and VT
10-point Borg scale) and the peripheral oxygen extraction must are pulmonary dead space and tidal
be ideal to assume a linear relationship volume, respectively (18, 26, 27). When
between V_ O2 and CO during exercise. plotting ventilation as a function of V_ CO2
During incremental exercise, the during incremental exercise, the slope of
ratio lower than 1.00 in the absence of ECG relative contribution of stroke volume to CO such a relationship (V_ E/V_ CO2 slope)
or hemodynamic abnormalities generally is dominant during the initial and describes the patient’s ventilatory efficiency
reflects submaximal cardiovascular effort. It intermediate phases of exercise. Thus, (i.e., the amount of air that must be
must be borne in mind, however, that oxygen pulse expressed as a function of ventilated to exhale 1 L of carbon dioxide)
patients with severely impaired exercise work rate has a typical hyperbolic profile, (Figure 4). The physiological meaning
tolerance can attain skeletal muscle strength with a rapid increase during the initial stages of V_ E/V_ CO2 slope is described by rearranging
exhaustion even earlier than central of exercise and a slow approach to an the above equation as follows: V_ E/V_ CO2 =
hemodynamic and ventilatory factors asymptotic value at the end of exercise. A 863/[ PaCO2 3 (1 2 VD/VT)]. Accordingly,
become limiting, interrupting exercise at flattening or downward displacement of V_ E/V_ CO2 slope will increase when PaCO2
peak respiratory exchange ratio values even oxygen pulse kinetics during incremental is reduced by hyperventilation and
lower than 1.00. Another possibility for lack exercise likely reflects peripheral vascular when VD/VT (i.e., wasted ventilation)
of an adequate respiratory exchange ratio perfusion or extraction or central is high. Another proposed cause of
increase during incremental exercise is cardiogenic performance limitations. increased V_ E/V_ CO2 slope is effort-induced
severe chronic obstructive lung disease, Among the latter, the development of muscle ergoreflex overactivation (28).
wherein lung hyperinflation can hinder exercise-induced myocardial ischemia can Normal values of V_ E/V_ CO2 slope
hyperventilation past the first ventilatory be present when a flattening or even show a progressive increase with
threshold (5). decrease of both the oxygen pulse increasing age (20) (Table 2). A higher
versus work rate (Figure 3) and V_ O2 than normal V_ E/V_ CO2 slope may be of
versus work rate relationships occur at undeterminable origin (i.e., primary
the same time (25). However, it is hyperventilation) or due to respiratory or
Oxygen Pulse important to understand that these cardiac diseases that induce a mismatch
abnormal responses are nonspecific of ventilation to perfusion. An increased V_ E/
Oxygen pulse is the V_ O2/heart rate ratio and and can also be seen in other conditions V_ CO2 slope is classically observed in patients
reflects the amount of oxygen consumed that might impair CO on response with chronic heart failure and in those with
per heartbeat (i.e., stroke volume multiplied during exercise. pulmonary hypertension of different
etiologies, with values progressively higher
with increasing disease severity (29–35).
16.0 Conversely, a downward displacement of the
V_ E/V_ CO2 slope occurs when the PaCO2 set
point is raised (i.e., in primary alveolar
12.0 hypoventilation).
O2 pulse (ml/beat)

8.0
Exercise Oscillatory Ventilation
Oscillatory ventilation during exercise is
4.0
a slow, prominent, consistent (rather
than random) fluctuation of ventilation
(Figure 5) that may occur in different
0
patterns (i.e., be present during the entire
0 20 40 60 80 100 120 140
duration of the exercise phase or only
WR (W)
during early or peak exercise) (36, 37).
Figure 3. Oxygen pulse as a function of work rate (WR) during ramp incremental exercise in a Several pathophysiological determinants
patient with coronary artery disease. The transition (dotted line) from a physiological increase to of this phenomenon have been proposed,
a decrease in oxygen pulse is considered a possible marker of exercise-induced myocardial which may be grouped into ventilatory
ischemia onset. See text for further details. (i.e., instability in the feedback ventilatory

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and associated with cyclic changes in arterial

2ndVT 2ndVT
60 oxygen and carbon dioxide tensions. Of
note, in this population, exercise oscillatory
ventilation is often associated with
nocturnal periodic breathing (40, 41).
40
VE (l/min)

F 4.4
CH = 4 Circulatory Power
e
op
Sl Cardiac power, the product of CO and mean
20
arterial pressure, is a powerful index of cardiac
N 28.1 systolic function (42). Circulatory power is a
p e= cardiac power surrogate obtainable from
S lo
cardiopulmonary exercise testing, calculated
0 as V_ O2 (in milliliters per kilogram per minute)
0 0.5 1.0 1.5 multiplied by systolic blood pressure (43).
VCO2 (l/min) Accordingly, circulatory power represents the
triple product of CO 3 C(a–v)O2 3 systolic
Figure 4. Ventilation (V_ E) as a function of volume of exhaled carbon dioxide (V_ CO2) during ramp blood pressure. Of note, unlike invasive
incremental exercise in a normal subject and a patient with chronic heart failure. A reduced ventilatory assessment of peak cardiac power, peak
efficiency is present in chronic heart failure, as witnessed by a steeper V_ E/V_ CO2 slope when compared circulatory power can be easily assessed
with that of a normal subject. 2ndVT = second ventilatory threshold; CHF = patient with chronic heart multiplying V_ O2Peak by peak systolic blood
failure; N = normal subject. pressure. Normal values of peak circulatory
power between 3,000 and 8,000 mm Hg 3
mL/kg/min are usually found according to
control system) and hemodynamic (i.e., persistence of an oscillatory ventilation age (Table 2), the highest values being found
(i.e., pulmonary blood flow fluctuations) pattern for at least 60% of exercise duration in young athletes and in patients with
(38). The criteria used to identify oscillatory at an amplitude higher than 15% of the hypertension with preserved systolic function.
ventilation during exercise suffer from lack average value of ventilation at rest). Circulatory power is an interesting
of standardization (39), with the most often Among patients with cardiac disease, parameter summarizing heart rate, stroke
adopted being those recommended by exercise oscillatory ventilation is specifically volume, blood pressure, and C(a–v)O2
the American Heart Association detected in those with chronic heart failure responses to exercise, all of which can be

90 Exercise Recovery

80

70

60
VE (L/min)

50 EOV

40

30

20

10

0
0 120 240 360 480 600 720 840 960 1080
Time (s)

Figure 5. Ventilation (V_ E) as a function of time during ramp incremental exercise in a patient with chronic heart failure. An oscillatory ventilatory pattern is
present during exercise, defined as cyclic fluctuations in V_ E lasting at least 60% of the exercise period, with an amplitude of fluctuations during exercise
higher than 15% of the average value of V_ E at rest. EOV = exercise oscillatory ventilation.

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PaCO2 ventilatory threshold is related to

40 pulmonary pressures and can thus provide
PETCO2
a noninvasive picture of disease severity
(32). Changes in PETCO2 may also be of
30 help in the detection of exercise-induced
PCO2 (mm Hg)

right-to-left shunting, as testified by (1) an

abrupt and sustained increase in partial
20 pressure of end-tidal oxygen with a
simultaneous sustained decrease in partial
pressure of end-tidal carbon dioxide, (2)
10 Expiration Inspiration an abrupt and sustained increase in the
respiratory exchange ratio, and (3) an
associated decline in pulse oximetry
0 saturation (46).
Time

Figure 6. Partial pressure of end-tidal carbon dioxide (PETCO2) in breathed air during a respiratory
cycle as a function of time. PETCO2 is the carbon dioxide partial pressure at the end of expiration, Conclusions
mirroring (but not being equal to) the partial pressure of alveolar and arterial carbon dioxide. The
difference between arterial carbon dioxide partial pressure (PaCO2) and PETCO2 is mainly due to
Cardiopulmonary exercise testing is a
mismatch of ventilation to perfusion.
methodology now widely available and
supported by sound scientific evidence in
several clinical fields. However, the full
altered in several pathophysiological ventilatory threshold and then decrease potential of this technique in the clinical
conditions, in particular, chronic heart as maximal effort is approached (5) and research setting still remains largely
failure. Even if not routinely assessed in (Table 2). Several investigations have underused. This may be due to several
the clinical setting, peak circulatory demonstrated a significant direct reasons, among which lack of measurements
power is a nice example of the possibility relationship between resting PETCO2 and standardization, nonuniform parameter
provided by cardiopulmonary exercise CO (44). The PETCO2 measured at first availability in cardiopulmonary exercise
testing to noninvasively explore left ventilatory threshold during incremental testing systems of different manufacturers,
ventricular systolic function during exercise has also been correlated with CO inability to easily interpret the obtained
incremental exercise. in patients with chronic heart failure (45) information in a way that is specific to test
and found to mirror disease severity in this indication, limited availability of data in
Partial Pressure of End-Tidal population. However, caution is required important subpopulations (such as women),
Carbon Dioxide in interpreting PETCO2 values in individual and inertia of professionals in the face of a
patients, as they may be affected by acute demanding methodology. Strong efforts and
The partial pressure of end-tidal carbon hyperventilation, increased dead space future investigations are needed to address
dioxide in exhaled air (PETCO2) is due to emphysema or other lung diseases, these issues and further promote the use of
commonly derived in mm Hg units or rapid and shallow breathing patterns, cardiopulmonary exercise testing in the
by cardiopulmonary exercise testing all of which will reduce the PETCO2 clinical and research setting. n
instrumentation (Figure 6). Normal independently of cardiac function.
values at rest range between 36 and In patients with pulmonary Author disclosures are available with the text
42 mm Hg, increase from rest to first hypertension, PETCO2 at rest and first of this article at www.atsjournals.org.

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Mezzani: CPET Basics S11