Arena and coworkers 1 questioned the interpretative power of maximum oxygen consumption per minute (VO_2max) for patients with heart failure and point to the enhanced prognostication of ventilatory markers. For the apparently healthy individual putting forth good exercise effort, VO_2max is the acknowledged best measure of cardiorespiratory fitness. It provides a measure of O₂ uptake by the respiratory system, O₂ transport by the cardiac system, and O₂ use by the peripheral musculature. A breakdown anywhere in this physiologic sequence results in a reduced VO_2max and a reduced classification of cardiorespiratory fitness. Test termination usually is because of volitional fatigue.

Unfortunately, the primary exertional limitation for many patients with chronic heart failure is dyspnea. For patients with heart failure, dyspnea on exertion is complex beyond merely an inability to generate cardiac output. If this were a straightforward condition, then the percentage ejection fraction of the left ventricle would be in strong association with VO_2max values, which is not the case. Therefore, as Arena and coworkers suggested, the ventilatory response to exercise may be a more defining prognostic indicator and marker of disease severity than VO_2max for patients with heart failure.

EXERCISE VENTILATION IN PATIENTS WITH HEART FAILURE

The difference between healthy subjects and those with heart failure is seen in the levels of exertion at which dyspnea begins. 2,3 Patients with heart failure uniformly demonstrate markedly increased minute ventilation, as compared with normal subjects, at a given workload because of pulmonary, peripheral, and central nervous system contributions. 4

[white square] Pulmonary influences include hemodynamic perturbations, ventilation-perfusion mismatching, and lung parenchymal changes, with resultant obstructive and restrictive physiology, changes in compliance, and decreased diffusion capacity.

[white square] Skeletal muscle changes produce fatigue, increased carbon dioxide and lactic acid production, and the need for increased oxygen delivery.

[white square] Respiratory muscle weakness, fatigue, and possibly ischemia lead to inefficient ventilatory patterns.

[white square] Direct central nervous system stimulation may directly produce the sensation of dyspnea.

Pulmonary Influences

A widely quoted hemodynamic model of dyspnea in heart failure asserts that decreased cardiac output produces increased pulmonary vascular pressures, creating interstitial and alveolar edema. On the surface, this explanation seems logical, but unfortunately it is not sufficient to explain the complexity of dyspnea in heart failure. In fact, there is a poor correlation of pulmonary capillary wedge pressure with subjective exertional dyspnea in patients with chronic heart failure. 5,6 In addition, interventions that aim to decrease filling pressures do not greatly ameliorate the perception of dyspnea or the increased ventilatory response. Furthermore, resting ejection fraction correlates poorly with exercise capacity, whereas ventilatory parameters demonstrate excellent correlation. 6

For heart failure patients, the inability to increase cardiac output adequately exaggerates the disparity in the perfusions of the upper and lower zones. Furthermore, the lower zones are more susceptible to interstitial edema and decreased compliance. Therefore, ventilation is reduced in these relatively well-perfused areas, which compounds the ventilation-perfusion mismatching and increases overall physiologic dead space. 7 Subsequently, the ventilatory inefficiency produced by ventilation perfusion mismatching contributes to the enhanced work of breathing and the exaggerated ventilatory response.

The hemodynamic sequelae of chronic congestive heart failure also seem to produce lung parenchymal changes. Histologic examination shows hypertrophy of the media in the pulmonary arteries, arterioles, and pulmonary veins, referred to as "muscularization of the arterioles" and "arterialization of the veins." 7 Another confounding variable is that many patients with heart failure have primary lung disease as well because smoking is a major risk factor in the development of both primary obstructive lung disease and ischemic cardiomyopathy. These chronic pulmonary changes in combination with more acute fluid displacement contribute to decreased lung compliance, airway obstruction, restrictive physiology, and diminished gas exchange.

Lung compliance is reduced in patients with heart failure secondary to histologic changes and edema, which increases lung stiffness. Therefore, increased intrathoracic negative pressures are required for distension of the lungs, which places a greater strain on the respiratory muscles and increases the work of breathing. These same histologic changes and peribronchial edema also result in airway obstruction and air trapping as interstitial edema increases peribronchial tissue pressures, causing early collapse of small, dependent airways. 8 In addition, the airways in patients with heart failure are more prone to bronchospasm, as evidenced by a more pronounced response to methacholine challenge. 7 Such airflow obstruction in patients with chronic heart failure, evident in both the chronic compensated and decompensated states, significantly increases the work of breathing. Parameters of obstruction correlate with ratings of perceived dyspnea and undoubtedly contribute to dyspnea and exercise limitation in patients with heart failure. 6

The same histologic changes and fluid transudation that result in decreased compliance and obstruction may lead to abnormalities in gas exchange. 9 Impaired gas exchange again decreases the efficiency of ventilation and increases the work of breathing. The resultant hypoxemia may directly promote the exaggerated ventilatory response via carotid body chemoreceptors. Additionally, tissue hypoxia may affect the earlier anaerobic threshold and earlier lactic acid production, further increasing ventilation.

Furthermore, with regard to the increased work of breathing, one unifying hypothesis proposed by Mancini et al 4 is that dyspnea results from increased demands on the respiratory muscles and an inability of the respiratory muscles to meet these demands due to weakness, decreased endurance, or ischemia.

Skeletal and Respiratory Muscular Adaptations

Histochemical and metabolic changes in the skeletal muscles have been well documented in patients with heart failure. These changes are presumed to be the consequence of deconditioning, malnutrition, chronic hypoperfusion, or neurohormonal insults. These changes include atrophy, a predominance of more easily fatigable glycolytic fibers, mitochondrial changes, and alterations in the levels of oxidative enzymes. 6 Whereas these alterations have been documented in peripheral skeletal muscles, they may affect the respiratory muscles as well.

Mancini and associates found measurements of maximal voluntary ventilation (MVV) and maximal sustainable ventilatory capacity (MSVC) to be lower in patients with heart failure than in healthy control subjects. 6 Interestingly, the ratio of measured MSVC to MVV was the same in patients and control subjects, whereas the predicted ratio of MSVC to MVV was markedly reduced in the heart failure group, suggesting decreased respiratory muscle endurance. The importance of the respiratory muscle dysfunction was highlighted by Mancini et al, 10 who demonstrated a marked improvement in respiratory muscle strength and endurance as a result of respiratory muscle training. More importantly, these gains in ventilatory function were accompanied by significant gains in exercise capacity and subjective improvement in perceived dyspnea. Moreover, findings show that improvements in MSVC correlate with improved exercise capacity resulting from exercise training. 11

With regard to breathing mechanics, decreased strength and endurance combined with decreased lung compliance and airway obstruction lead to inefficient respiratory patterns (rapid and shallow respiration). This pattern decreases the energy expenditure for any single breath, but is less efficient overall because it contributes to relatively lower tidal volumes, higher respiratory rates, and increased dead space ventilation. Such inefficient ventilation also contributes to the exaggerated ventilatory response to exercise in patients with heart failure, as compared with healthy subjects. 5

Central Nervous Stimulation

In patients with heart failure, the enhanced neural input 7 producing dyspnea is derived from receptors located in multiple organ systems, all contributing to the following aspects of exaggerated ventilation:

[white square] vascular baroreceptors responding to elevated filling pressures

[white square] chemoreceptors triggered by hypoxia

[white square] central nervous system input derived from medullary responses to carbon dioxide and acidemia

[white square] skeletal and respiratory muscle mechanoreceptors sensing the degree of exertion and fatigue

[white square] pulmonary perivascular proprioreceptors (J fibers) stimulated by vessel distention

[white square] cortical inputs responding to anxiety and anticipation.

Thus, the simple hemodynamic model is only part of a complex, intertwined physiologic puzzle including pulmonary, skeletal muscle, and central nervous system responses to heart failure, supporting the need for close scrutiny of ventilation during exercise in the patient with heart failure.

SUPPORTIVE RESEARCH

Previously, supportive evidence from the research of Chua et al 12 showed that a high minute ventilation/carbon dioxide output slope selects patients with more severe heart failure and is an independent predictor of prognosis, specifically a slope exceeding 34. In agreement with the complexity of the VE response to exercise in the patient with heart failure, these authors stated that the increased VE is predominantly attributable to reduced pulmonary perfusion and hemodynamic abnormalities causing ventilation-perfusion mismatching, or to the altered control of ventilation, as suggested by augmentation in chemosensitivity. Demonstrated to be inversely related to peak oxygen consumption, the increased ventilatory response is multifactorial. The physiologic multiplicity of the VE response supports its use as a supplemental index in the clinical assessment of patients with heart failure.

SUMMARY

The exaggerated ventilatory response in patients with heart failure is clearly multifactorial and complex beyond a mere reduction in pulmonary blood flow. Pulmonary dysfunction, including ventilation-perfusion mismatching, decreased lung compliance, restriction, airway obstruction, decreased diffusion capacity, and decreases in respiratory muscle strength and endurance, contributes to an inefficient breathing pattern and increased work of breathing. This is further compounded by the limited ability of the failing heart to meet the metabolic demands of the respiratory muscles, leading to underperfusion and ischemia.

Although VO_2max has important implications with regard to functional capacity, exercise test personnel must be knowledgeable concerning the clinical physiology of ventilation during exercise in the patient with heart failure. Ventilatory markers, as Arena and coworkers have demonstrated, are most indicative of disease severity and enhance the prognostic value of the test results.

References