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Editorial Comment

Cardiology 2009;114:244246
DOI: 10.1159/000232406

Received: June 16, 2009

Accepted: June 19, 2009
Published online: August 7, 2009

Noninvasive Cardiac Output

Measurement: A New Tool in Heart
Piergiuseppe Agostoni a, b Gaia Cattadori a

Department of Cardiovascular Sciences, Monzino Cardiology Center, IRCCS, University of Milan, Milan, Italy;
Division of Respiratory and Critical Care Medicine, Department of Medicine, University of Washington,
Seattle, Wash., USA

The great majority of clinicians consider peak exercise

oxygen uptake (VO2) as one of the most useful variables
to predict the outcome of heart failure (HF), to evaluate
HF severity and (except for -blockers) to assess efficacy
of therapy, too. In the early report of Weber and Janicki
[1], in the mid-1980s, VO2 was associated with hemodynamic impairments. Later, several authors reported that
hemodynamic exercise testing, mainly cardiac output
(CO) levels during exercise, was even more useful than
VO2 alone [24]. Unfortunately, at that time, hemodynamic monitoring was only accomplished with invasive
techniques, rendering this type of exercise test uncomfortable and possibly dangerous for patients, and expensive. Therefore, it was unlikely to be frequently repeated
to assess HF evolution and response to treatment. Consequently, hemodynamic evaluation during exercise never reached everyday clinical practice. Exercise CO has
been estimated from several other noninvasively obtained parameters, but none was really satisfactory, and
no hemodynamic measurement has reached the clinical
field [5, 6].
It is extremely important to study new methods to
measure CO noninvasively, as it is reported by Saur et al.
[7] in the present issue of Cardiology. Among different
noninvasive techniques, the authors chose inert gas rebreathing (IGR), which has become a simple and easy-touse technique for measuring CO only with the recent in 2009 S. Karger AG, Basel
Fax +41 61 306 12 34

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troduction of a small, portable device (Innocor rebreathing system; Innovision, Odense, Denmark). The IGR
technique uses an oxygen-enriched mixture of an inert
soluble gas (0.5% N2O) and an inert insoluble gas (0.1%
SF6) from a prefilled bag. Patients breath into a respiratory valve via a mouthpiece and a bacterial filter with a
nose clip. At the end of expiration, the valve is activated
so that patients will rebreathe from the prefilled bag for
a period of 1020 s. After this period, patients are switched
back to ambient air and CO measurement is terminated.
Photoacoustic analyzers measure gas concentrations over
a 5-breath interval. SF6 is insoluble in blood and it is used
to determine lung volume. N2O is soluble in blood and its
concentration decreases during rebreathing with a rate
proportional to pulmonary blood flow. The IGR technique is a safe, precise, repeatable and cheap tool to measure pulmonary blood flow and, more precisely, the portion of pulmonary blood flow which is involved in gas
exchange. Shunt flow in the lung can be estimated [7] and
this estimation is reliable, provided that arterial oxygen
saturation is within the normal range. The strength of the
paper by Saur et al. [7] is that it is a large-scale report with
almost 400 individuals studied at rest.
However, a further step ahead might be of advantage,
i.e. to measure CO during exercise noninvasively. Few reports showed that this is now possible using the IGR even
in HF patients [8, 9]. However, why should we push the
Piergiuseppe Agostoni
Department of Cardiovascular Sciences
Monzino Cardiology Center, IRCCS, University of Milan
via Parea 4, IT20138 Milan (Italy)
Tel. +39 02 5800 2299, Fax +39 02 5800 2283, E-Mail

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Subject B
Subject A

Arteriovenous oxygen difference (ml/100 ml)

VO2 (l/min)

CO (l/min)



HF Doctor Community to measure CO during exercise

and possibly at peak exercise? First of all, as previously
stated, because CO at peak exercise and its increase during submaximal exercise are both strong prognosticators
of HF and a tool to assess the efficacy of HF treatment
[24]. Secondly, and very importantly from a clinical
point of view, because we will, eventually, be able to avoid
the nasty comments on a cardiopulmonary exercise test
of an HF patient such as a test suggestive of muscle deconditioning or the role of muscle deconditioning in reducing exercise performance cannot be quantified. Indeed, up to now, the only proof of the presence of deconditioning and its role in a patients exercise limitation is
the evaluation of exercise improvement with physical
training. Consequently, the possibility to measure CO
and VO2 simultaneously during exercise paves the way
for a new approach to evaluate HF.
Regardless of the method used, applying the Fick
equation, measurement of VO2 and CO enables to split
VO2 into its two determinants: CO and the difference in
the arteriovenous oxygen content (avO2). Thus, it is
possible to graphically analyze the Fick equation during
exercise and to assess how a patient is performing. For
example, for a given VO2, it is now possible to differentiate a trained HF patient, reported in the graph as subject
A (fig. 1), who has a high avO2 and a low CO, with an
untrained HF patient (subject B), who has a low avO2
and a relatively high CO. In our opinion, application of
the Fick principle in the clinical field will likely allow a
better selection of patients for appropriate treatment, e.g.
for cardiac rehabilitation, cardiac resynchronization
therapy and cardiac transplantation. Indeed, knowing
VO2, CO and avO2 as well as the predicted value of each

of these three variables allows us to calculate how much

of the VO2 reduction is due to CO and/or to avO2.
Therefore, a patient with low VO2 with some reduction in
exercise CO and low avO2 will likely have more benefit
from cardiac rehabilitation than a subject with the same
VO2 but a greater reduction in CO and a higher avO2,
who will probably benefit more from cardiac resynchronization therapy.
Furthermore, the calculation of avO2 provides us
with a tool to understand the restricted exercise capacity
of HF patients separating muscle function from anemia.
Indeed, avO2 depends on the hemoglobin concentration, arterial pO2 and the capability of muscles to extract
O2. The role of hemoglobin can be assessed considering
that in systemic arteries of normoxic HF patients, hemoglobin usually carries 1.34 ml of O2, and because O2 extraction rate is 70% [10] at peak exercise, each gram of
hemoglobin provides 1 ml of O2 to muscles. Consequently, because CO is now easily measurable [79], we
know how much VO2 is related to hemoglobin and, more
importantly, assuming a normal hemoglobin concentration of 15 g/dl, it is possible to calculate the VO2 deficit
at peak exercise due to anemia. Of note, anemia is frequently observed in HF patients and evidence exists that
anemia is one of the major determinants of HF outcome.
In conclusion, the possibility to measure CO noninvasively is of utmost importance [7]. The simultaneous evaluation of VO2, CO and avO2 at peak exercise is a new
tool to assess HF, assisting physicians in the difficult task
of defining the role of exercise limitation in muscle deconditioning and anemia, and, overall, of tailoring the
best treatment for each patient.

Noninvasive CO Measurement

Cardiology 2009;114:244246


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Fig. 1. Graphic representation of the Fick principle.



5 Stringer WW, Hansen JE, Wasserman K:

Cardiac output estimated noninvasively
from oxygen uptake during exercise. J Appl
Physiol 1997;82: 908912.
6 Cohen-Solal A, Tadet JY, Logeart D, Bourgoin P, Tokmakova M, Dahan M: A non-invasively determined surrogate of cardiac
power (circulatory power) at peak exercise
is a powerful prognostic factor in chronic
heart failure. Eur Heart J 2002;23:806814.
7 Saur J, Fluechter S, Trinkmann F, Papavassiliu T, Schoenberg S, Weissmann J, Haghi D,
Borggrefe M, Kaden JJ: Noninvasive determination of cardiac output by the inert-gasrebreathing method comparison with cardiovascular magnetic resonance imaging.
Cardiology 2009;114:247254.

Cardiology 2009;114:244246

8 Agostoni PG, Cattadori G, Apostolo A, Contini M, Palermo P, Marenzi GC, Wasserman

K: Noninvasive measurements of cardiac
output during exercise by inert gas rebreathing technique: a new tool for heart failure
evaluation. J Am Coll Cardiol 2005;46:1779
9 Lang CC, Karlin P, Haythe J, Tsao L, Mancini DM: Ease of noninvasive measurement
of cardiac output coupled with peak VO2 determination at rest and during exercise in patients with heart failure. Am J Cardiol 2007;
10 Perego G, Marenzi G, Guazzi M, Sganzerla P,
Assanelli E, Palermo P, Conconi B, Lauri G,
Agostani P: Contribution of PO2, P50, and
Hb to changes in arteriovenous O2 content
during exercise in heart failure. J Appl Physiol 1996;80:623631.

Agostoni /Cattadori

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