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(Circulation. 2000;101:2774.)
© 2000 American Heart Association, Inc.

Editorial

Gas Exchange Efficiency in Congestive Heart Failure

Robert L. Johnson, Jr, MD

From the Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex.

Correspondence to Robert L. Johnson, Jr, MD, Pulmonary and Critical Care, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9034.

Key Words: Editorials • exercise • dyspnea • hyperpnea • blood gases

The lungs and heart are irrevocably linked in their oxygen and CO₂ transport functions. Functional impairment of the lungs often affects heart function, and functional impairment of the heart often affects lung function. In patients with chronic congestive heart failure (CHF), exertional dyspnea is a common symptom, and ventilatory effort is increased at a given exercise workload despite normal arterial blood gases. In this issue of Circulation, the increased exercise ventilation in CHF is reported to contain prognostic information that extends beyond that provided by maximal oxygen uptake (O_2max), left ventricular ejection fraction, or the NYHA functional classification.¹ Their data indicate that the steepness with which ventilation increases relative to CO₂ production during incremental exercise, either alone or in combination with O_2max, left ventricular ejection fraction, and NYHA classification, can be a sensitive tool for predicting event-free survival of patients with CHF. Such a tool can be important for evaluating the need for heart transplantation or for following the efficacy of therapeutic measures; it can be evaluated at submaximal work loads and is easier to measure than O_2max.

The high ventilation (E) with respect to CO₂ production (CO₂) in CHF is not a new observation,^{2 3 4 5 6} but its potential usefulness as a prognostic tool to evaluate the severity of CHF is relatively new. Perhaps even more important, however, is what the studies of Kleber et al,¹ using this tool, tell us about impaired gas exchange in CHF and its relationship to impaired gas exchange in lung disease.

Because the high level of ventilatory drive in heart failure can predict survival, it must contain important information on how left ventricular dysfunction affects either the lung or ventilatory control. The first thing that we need to examine, then, is what basic information is contained in the slope of the relationship between ventilation (E) and CO₂ production (CO₂). The modified alveolar equation⁷ concisely describes the determinants of the steepness with which E rises with respect to CO₂:

The relationship between E and CO₂ by Equation 1 is linear over a wide range, and its slope is determined by just 2 factors: (1) behavior of arterial CO₂ tension during exercise and (2) the VD/VT ratio. If PaCO₂ is driven down by a high ventilatory drive from peripheral chemoreceptors or by ergoreceptors in skeletal muscle, the slope of the E/CO₂ relationship will increase, or if VD/VT is high, the E/CO₂ slope will increase. Increased chemoreceptor gain is often seen in severe CHF,⁸ eg, in patients with Cheyne-Stokes breathing, but increased chemoreceptor gain alone will not drive the PaCO₂ down unless the set point about which PaCO₂ is controlled is depressed or unless hypoxic drive or ergoreceptor drive is high. Most studies suggest that blood gases are normal in patients with CHF⁴ and that PaCO₂ either stays the same or declines modestly from rest to peak exercise, no differently than in normal controls. There are 2 potential sources for a high VD/VT ratio: (1) a low tidal volume (VT) with respect to a normal anatomic dead space or (2) an abnormally high physiological dead space. Patients with CHF often have a reduced tidal volume at heavy exercise, which would increase the VD/VT ratio; however, it has been estimated that only 33% of the increased dead space ventilation in CHF can be explained by a low VT.^{2 5}

Current information suggests that the major source for an abnormally steep E/CO₂ slope in CHF is increased nonuniformity of ventilation-perfusion ratios (/), causing inefficient gas exchange. However, a word of caution is still necessary. The above conclusion is based on indirect evidence. No direct comparisons have been made of PaCO₂ and dead space ventilation in CHF patients with and without a high E/CO₂ slope during exercise. Such comparisons are needed.

What might be the source of an increased nonuniformity of pulmonary / ratios in CHF and why would it provide prognostic information not provided by O_2max? Lung volumes and ventilatory function in the CHF patients studied by Kleber et al¹ were relatively normal, and arterial blood oxygen saturation at peak exercise was normal, as is generally the case in CHF in the absence of coexisting lung disease. This pattern of a high VD/VT ratio with normal arterial blood gases suggests that nonuniformity of / ratios in the lung is more likely caused by increased nonuniformity of perfusion than of ventilation. When ventilatory capacity remains normal, inefficient gas exchange caused by abnormal distribution of perfusion usually can be well compensated during exercise by raising ventilation enough to maintain a normal PaCO₂ and normal arterial blood O₂ saturation. This is not true in severe chronic obstructive lung disease, in which not only are ventilation and perfusion poorly matched, but also, compensatory increases in ventilation are restricted by the high resistance to air flow; during exercise, PaCO₂ rises and arterial blood O₂ saturation falls. In the CHF patients studied by Kleber et al¹ with high E/CO₂ slopes, mean total lung capacity (TLC), vital capacity (VC), and lung diffusing capacity (DLCO) were significantly lower than in patients with a normal E/CO₂ slope, yet arterial O₂ saturation remained normal at peak exercise. DLCO is usually reduced in severe CHF^{9 10 11 12} and correlates significantly with O_2max. A modest reduction in DLCO may reflect a more severe reduction of true membrane diffusing capacity (DMCO), because the low DMCO in CHF can be counterbalanced by a high pulmonary capillary blood volume (Vc). In patients with severe CHF (NYHA class III) studied by Puri et al,⁹ DMCO was 35% of control, whereas DLCO was reduced only to 55% of control because of a high Vc (144% of control). The low DMCO implies that oxygen diffusing capacity (DLO₂) is correspondingly reduced, which in turn will reduce the rate of oxygenation of blood perfusing the lungs, and if the cardiac output is high enough, will cause oxygen saturation of blood leaving the lung to fall during exercise. Some of these changes in diffusing capacity and dead space ventilation are reversible with ACE inhibitors and diuretics, reflecting subclinical interstitial pulmonary edema.^{5 13} However, persistence of a low DLCO after heart transplantation¹⁴ implies additional structural changes in microvasculature, which is confirmed by morphological studies. Muscular arteries and arterioles show medial hypertrophy and intimal and adventitial fibrosis with narrowing vascular lumens.¹⁵ Matrix proteins are increased in the alveolar walls, and capillary basement membranes are thickened^{16 17} ; these changes probably begin very early in response to a chronic increase in pulmonary capillary blood pressure from any cause.¹⁸

In the face of an abnormally high VD/VT ratio and a significant reduction of DLO₂ in patients with severe CHF, why is maximal oxygen transport not partially limited by impaired gas exchange associated with a rise in PaCO₂ and fall in arterial O₂ saturation during exercise, as usually occurs in lung disease with similar abnormalities? There are 2 reasons: (1) Maximal ventilatory capacity is well maintained in CHF and can compensate for the high VD/VT, bringing the PaCO₂ down to normal levels at peak exercise and maintaining a normal or high alveolar oxygen tension. (2) Maximal cardiac output (_max) in CHF is reduced more than is the DLO₂; hence, the ratio of DLO₂/ never falls low enough during exercise to cause a fall of O₂ saturation of blood leaving the lung.⁷

It is the low maximal cardiac output and impaired peripheral O₂ extraction that primarily impairs oxygen transport in CHF,^{4 19} not pulmonary gas exchange; arterial blood gases remain normal. However, the reduced efficiency of gas exchange in CHF reflected by the steep relationship between E and CO₂ is probably a major source of the exertional dyspnea with normal arterial blood gases.

Thus, left ventricular heart failure has important effects on lung function, just as lung disease has important effects on cardiovascular function. The application of a measurement that quantifies efficiency of gas exchange during exercise as an index of the severity of CHF and life expectancy in CHF emphasizes the important functional linkage between the heart and the lungs. The measurement used is simple and can be applied even at low levels of exercise. It must be emphasized, however, that the measurement, ie, the slope of the relationship between E and CO₂ during exercise, is nonspecific and is frequently abnormally steep in primary lung disease as well as in CHF, although usually associated with abnormal arterial blood gases in lung disease. Hence, the measurement used by Kleber et al¹ must be interpreted in context. To emphasize this, a comparison of the primary determinants of impaired gas exchange in CHF, chronic obstructive lung disease, and interstitial lung disease with alveolar capillary block²⁰ are shown in the Table.

View this table: [in this window] [in a new window]   Table 1. Determinants of Gas Exchange at Maximal Exercise in Patients With CHF and With Primary Lung Disease

In the Table, the arrows, pointing either up or down, indicate the change in direction of the key determinants at each step in oxygen transport for each condition. The Table is oversimplified but is conceptually useful. In CHF, the primary impairment of oxygen transport is imposed by a reduced maximal cardiac output (_max), indicated by a boldface arrow pointing down. In patients with chronic obstructive pulmonary disease, primary impairment of oxygen transport is imposed by a reduced maximal ventilation (E_max) with inefficient gas exchange, and in patients with interstitial lung disease with alveolar capillary block, the primary impairment is imposed by a reduced DLO₂. In all of these disorders, uneven / matching increases the VD/VT ratio and impairs the efficiency of CO₂ excretion from the lung; if ventilation can be increased enough during increasing exercise to prevent the PaCO₂ from rising, the E/CO₂ slope will be steeper than normal in lung disease as well as in CHF, as indicated by the bracketed term in Equation 1. In severe chronic obstructive pulmonary disease, PaCO₂ will rise as exercise load increases, and the E/CO₂ slope may become low even though VD/VT is high.¹⁹ Coexistent lung disease can significantly alter the expected pattern of gas exchange in CHF. Thus, it must be cautioned that if a patient with CHF has significant coexistent lung disease, application of the E/CO₂ slope to predict survival, as proposed by Kleber et al,¹ becomes invalid.

In summary, available data suggest that chronic CHF induces structural changes as well as interstitial pulmonary edema in the lungs, which impair the efficiency of gas exchange; the extent of these changes reflects the severity of the CHF and probably its duration. Physiologically, these structural changes are manifested by an increased ratio of dead space to tidal volume (VD/VT), which causes an abnormally high ventilation during exercise. They are also usually manifested by a reduction in diffusing capacity of the lung (DLCO), which varies with the severity of CHF. Although the magnitude of these physiological changes in lung function can reflect the severity of CHF and be an important predictor of survival, inefficiency of gas exchange is not the primary cause of impaired exercise capacity. Reduced maximal oxygen transport in CHF is caused by a low maximal cardiac output and perhaps impaired peripheral oxygen extraction; arterial PaCO₂ and arterial O₂ saturation at peak exercise remain normal. Even though arterial blood gases remain normal, inefficient gas exchange can be a major source of exertional hyperpnea and dyspnea. The pattern of abnormal gas exchange during exercise in CHF clearly differs from that in primary lung disease; problems of interpretation arise when CHF and primary pulmonary disease coexist.

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

References

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