Alveolar-capillary membrane conductance is the best pulmonary function
correlate of exercise ventilation efficiency in heart failure patients
Marco Guazzia,*, Giuseppe Reinab, Gabriele Tumminelloa, Maurizio D. Guazzic
aCardiopulmonary Laboratory, University of Milano, Cardiology Division, San Paolo Hospital, Via A. di Rudinı ´, 8, 20142, Milano, Italy
bInstitute of Statistics and Biometry, University of Milano, Milano, Italy
cInstitute of Cardiology, University of Milano, Milano, Italy
Received 6 April 2004; received in revised form 29 July 2004; accepted 14 October 2004
Available online 23 March 2005
Background: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an
increased exercise ventilation to CO2production (VE/VCO2) slope is undefined.
Methods: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity
(FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing
capacity with its subcomponents (alveolar-capillary membrane conductance (Dm) and capillary blood volume (Vc)).
Results: Patients showed a mild restrictive pattern (FEV1=85F15% and FVC=75F13% of normal predicted) and a moderate Dmreduction
(32F12 ml min?1mm Hg?1). Average peak VO2was 15.6F4.0 ml min?1kg?1and the VE/VCO2slope was 39.6F11.0. At simple
Spearman correlation analysis, all variables, but Vc, correlated with peak VO2; only Dmcorrelated with VE/VCO2slope. At partial Spearman
correlation, all variables lost the peak VO2correlation, and Dmstill inversely correlated with VE/VCO2slope (r=?0.35; p=0.005). In
patients with a high VE/VCO2slope (cutoff value 34), despite comparable lung volumes, Dmwas significantly more depressed (30F13 vs.
35F10 ml min?1mm Hg?1; pb0.01).
Conclusions: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. Dmimpairment rather than lung
volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas
exchange in HF patients.
D 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Keywords: Alveolar-capillary gas diffusion; Exercise ventilation; Left ventricular dysfunction
Lung volumes and pulmonary gas diffusing capacity at
rest correlate with a reduced oxygen uptake at peak
exercise (peak VO2) in patients with heart failure (HF) due
to left ventricular (LV) systolic dysfunction [1–4]. Several
investigators have described an excessive ventilatory
response to exercise, expressed by the slope of the linear
relationship of ventilation per unit of carbon dioxide
production (i.e. VE/VCO2slope), as a common pathophy-
siological characteristic of these patients, that provides
strong and independent prognostic information [5–11]. A
cause–effect relationship has been established between a
peripheral chemoreflex hypersensitivity and a steep exer-
cise VE/VCO2slope [5,9,12,13]. Mathematically, the VE/
VCO2 slope is determined by three factors: the amount
of CO2 produced, the physiological dead space–tidal
volume ratio (VD/VT) and the arterial CO2 partial
pressure. This implies that abnormalities intrinsic to the
lung and commonly encountered in HF patients, such as a
restrictive lung pattern [14–17], and an abnormal gas
diffusing capacity [2,3,18], may also be involved in the
dynamic ventilatory response to exercise. On the other
1388-9842/$ - see front matter D 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Tel.: +39 2 50323144; fax: +39 2 50323144.
E-mail address: Marco.Guazzi@unimi.it (M. Guazzi).
The European Journal of Heart Failure 7 (2005) 1017–1022
by guest on June 9, 2013
 Guazzi M. Alveolar-capillary membrane dysfunction in chronic heart
failure: pathophysiology and therapeutic implications. Clin Sci
 Guazzi M, Pontone G, Brambilla R, Agostoni PG, Re `ina G. Alveolar-
capillary membrane gas conductance: a novel prognostic indicator in
chronic heart failure. Eur Heart J 2002;23:467–76.
 Beaver WL, Wasserman K, Whipp BJ. A new method for detecting
the anaerobic threshold by gas exchange. J Appl Physiol 1986;60:
 American Thoracic Society. Standardization of spirometry: 1987
update. Am Rev Respir Dis 1987;136:1285–98.
 Hankinson JL, Odenerantz JR, Fedan KB. Spirometric reference
values from a sample of the general US population. Am J Respir Crit
Care Med 1999;159:179–87.
 Roughton FJW, Forster FE. Relative importance of diffusion and
chemical reaction rates in determining rate of exchange of gases in
human lung, with special reference to true diffusing capacity of blood
in the lung capillary. J Appl Physiol 1957;11:290–302.
 Sullivan M, Higginbotham M, Cobb F. Increased exercise ventilation
in patients with chronic heart failure: intact ventilatory control despite
hemodynamic and pulmonary abnormalities. Circulation 1988;77:
 Guazzi M. Alveolar-capillary membrane dysfunction in chronic
heart failure. Evidence of a pathophysiological role. Chest
 Agostoni PG, Guazzi M, Bussotti M, Grazl M, Palermo P, Marenzl G,
et al. Lack of improvement of diffusing lung capacity following fluid
withdrawal by ultrafiltration in chronic heart failure. J Am Coll
 Guazzi M, Agostoni PG, Guazzi MD. Modulation of alveolar-capillary
sodium handling as a mechanism of protection of gas transfer by
enalapril, and not by losartan, in chronic heart failure. J Am Coll
M, et al. Ventilation and diffusion abnormalities in long-term survivors
after orthotopic heart transplantation. Chest 1999;115:1314–5.
 Wasserman K, Zangh YY, Gitt YY, et al. Lung function and exercise
gas exchange in chronic heart failure. Circulation 1997;96:2221–7.
M. Guazzi et al. / The European Journal of Heart Failure 7 (2005) 1017–1022
by guest on June 9, 2013