Cardiac and pulmonary disease frequently coexist in the dyspneic patient. However, evaluation of these patients may frustrate physicians who are faced with vague clinical clues and laboratory tests which fail to delineate the cause of the exercise limitation. In this situation, cardiopulmonary stress testing has two functions, to characterize the exercise limitation and to assess response to treatment. Abnormalities which were underestimated or not clinically appreciated may be demonstrated by monitoring the response to exercise of such parameters as heart rate, cardiac output, ventilation, and gas exchange. These parameters are used to characterize the limitation as primarily cardiac, pulmonary or both. Furthermore, repeat testing provides the physician with quantitative data for assessing effectiveness of therapy. Repeat exercise evaluation may be particularly valuable in combined cardiopulmonary disorders since the response to treatment of one disease may unmask exercise-limiting symptoms from another. For example, treatment of moderately severe COPD may allow exercise tolerance to increase until limitation by chest pain from coronary artery disease occurs. Conversely, progression of lung disease in a patient who also has angina may cause exercise to cease from ventilatory limits before chest pain from myocardial ischemia occurs.
In recent years, the availability of computerized laboratory equipment has made measurement of pulmonary gas exchange during exercise available to most cardiologists and pulmonologists. Similarly, the development of radionuclide computer-assisted cardiac imaging and echocardiography has made widespread use of noninvasive cardiac function studies possible. The combined use of these techniques offers the clinician a powerful tool for the noninvasive evaluation of patients with exercise limitation. In order to interpret the results of exercise testing in combined cardiac and pulmonary disease, one must understand the characteristic responses seen with relatively pure disease of each system. The purpose of this review is to present an overview of the practical aspects of noninvasive incremental exercise testing in cardiac and pulmonary disease.
Measurement of Pulmonary Gas Exchange
Measurement of pulmonary gas exchange provides data points which, when analyzed in concert, allow characterization of the physiologic response to exercise. The primary measurements are the rate of oxygen consumption (VoJ, the minute ventilation (Ve), and the rate of carbon dioxide production (Vco2). These values are compared to the predicted normal values, and related to one another to produce the characteristic patterns found in normal and diseased states. All three measurements are used to determine the anaerobic threshold (AT) which is important in evaluating the cardiovascular response to incremental exercise.
Oxygen Consumption (Vo)
As the body begins exercise, the muscles require increasing amounts of oxygen to do work. The delivery of oxygen depends upon increasing cardiac output and vasodilatation to enhance perfusion of the working muscles by oxygenated blood. In a progressive maximal exercise test the Vo2 linearly parallels the increase in cardiac output and work performed until a plateau is reached at the maximal cardiac output. In normal individuals, the limits of exercise are determined by the cardiovascular system’s ability to continue to provide oxygen to the tissues, since the pulmonary vascular bed expands and ventilation increases to maintain adequate gas exchange even under strenuous exercise. Therefore, measurement of the Vo2 gives a rough estimate of the power output of the exercising cardiovascular system and is used to assess its performance. The Vo2 may be expressed in L/min or related to the lean body weight, ml/min/kg. The maximum oxygen uptake (Vo2max), or aerobic capacity, occurs when increasing the work rate results in no further increase in oxygen consumption. An acceptable definition is an increase of less than 1 ml/min/kg for 60 seconds over the previous load. If exercise stops prior to reaching maximal cardiac output, Vo2max is not reached, but the term is sometimes confusingly applied to the highest achieved Vo2. In this article, the term Vo2max will apply to the definition given here, and other references are to the maximal attained Vo2.
Estimations of the Vo2max based on treadmill time or ergometer workload may be subject to error in patients with disease, so measurement of this value is preferable. Normal subjects are expected to exceed 90 percent of the predicted Vo2max for their age. A decrease in the maximal attained Vo2 from predicted will be found in significant exercise limitation of any cause. However, assessment of the maximal attained Vo2 in relationship to the minute ventilation (VEmax), heart rate, C02 production and body weight can help define the limitation as predominantly cardiovascular or pulmonary in origin.
As stated above, the Vo2max is related to the limits reached by the cardiac output. Expressed mathematically, the cardiac output is defined by the Fick equation as:
Q = W(CaO2-CvO2) where Q = cardiac output, and (CaO2 — CvOa) = arterial and mixed venous oxygen content difference. Cardiac output is also represented as the product of the stroke volume (SV) and the heart rate (f):
Q = SVxf.
We can combine these formulas to yield: fayf = SV (Ca02 – CvO2).
Since the (Ca02 — Cv02) remains fairly constant, Vo2 is approximately proportional to the stroke volume during exercise. This value is known as the Oa pulse. It actually indicates the amount of oxygen consumed per heart beat and is expressed as ml/beat. The normal predicted values are obtained by dividing the predicted maximal Vo2 by the predicted maximal heart rate.
Most cardiac disorders limiting exercise cause a decreased O2 pulse, since the SV is often low and cardiac output is maintained by an increase in heart rate. However, any condition that causes exercise to cease at a low Vo2 with a higher than predicted heart rate will produce a low 02 pulse. Similarly, the heart rate for a particular Vo2 may be low due to disease, pacemaker, or medications such as beta blockers, and produce a falsely normal 02 pulse. Therefore, it is best to examine the value of the Vo2 before the O2 pulse.
Many patients with mild coronary artery disease (CAD) have a decreased maximum attained Vo2 due to cessation of exercise because of chest pain without evidence of a decrease in cardiac output. Mild CAD and mild cardiac valvular diseases are associated with normal responses to exercise of Vo2, cardiac output and SV. Advanced CAD will produce a more significantly decreased Vo2max but is indistinguishable from other causes of heart failure. Similarly, cardiovascular deconditioning may produce a low Vo2 and 02 pulse which cannot be distinguished from mild heart failure. Patients with significant cardiac dysfunction will cease exercise at a lower than predicted Vo2max due to a decreased cardiac output. The SV fails to increase normally due to decreased contractility of the myocardium while the cardiac output is initially maintained by an increase in heart rate. With more significant impairment of cardiac function, the maximum attained Vo2 is further decreased and accompanied by evidence of increased muscle anaerobic metabolism due to the sustained low cardiac output at relatively low workloads. Hence, changes in function through time can be quantitatively assessed by repeat exercise testing which may be used to guide response to therapy or assess need for further intervention. In patients with known heart failure, Weber et al have shown that the Vo2max has been found to reliably classify the severity of the disease when combined with the measurement of the anaerobic threshold (Table 1).
The Vo2 at maximal exercise in pulmonary disease varies widely, since the primary limitation to exercise is usually impaired ventilation or gas exchange. Although patients with mild COPD may have no significant decrease in Vo2, patients with more severe disease will cease exercise at a low Vo2. However, they will demonstrate other coexistent abnormalities such as an inappropriately high Ve or dead space to tidal volume ratio (Vd/Vt). Patients with severe COPD usually have a normal cardiac output for the level of VOa, which differs from the patient with cardiac disease. However, the 02 pulse is often low in COPD patients due to accelerated heart rates from medications, associated cardiac deconditioning, or right ventricular dysfunction. * Similarly, patients with mild interstitial lung disease will have a normal Vo2 and 02 pulse, but as the severity of the disease progresses, exercise will cease at a lower Vo2 due to ventilatory limitations or hypoxemia.
Comparing responses in cardiac and pulmonary disease, Nery et al found the oxygen pulse in patients with mitral valve disease (MVD) to be significantly lower than both normal subjects and patients with COPD. However, the aerobic capacity expressed as the VO1/kg at maximal exercise was lower than normal for patients with COPD and MVD, but there was no significant difference between the two groups. This suggests that the Vo2 alone cannot be used to distinguish between cardiac and pulmonary disease. This may be particularly important with coexistent COPD and coronary artery disease. In such cases, careful observation of the response to exercise of ventilatory mechanics, gas exchange and anaerobic threshold should help to delineate which one is causing the limitation. Examination of the maximal Vo2 and 02 pulse is not sufficient.
Figure 1 shows a graphic representation of pulmonary gas exchange data from three typical subjects studied in our laboratory. One subject is normal while the other two have severe COPD and CHF respectively. The Vo2 is represented on the top row of graphs. The normal individual reached the predicted value of Vo2max for his age, while the highest attained Vo2 for the subjects with cardiac and pulmonary disease was considerably lower. The second row of graphs in Figure 1 shows the 02 pulse during the same studies. Again, the low 02 pulse distinguishes the patients with disease from normal, but not from one another. The remaining data in Figure 1 will be discussed below.
Table 1—Grading the Severity of Circulatory and Cardiac Failure According to Aerobic Capacity and Anaerobic Threshold
|Severity||Class||Vo2 max (ml/min/kg)||AnaerobicThreshold(ml/min/kg)||MaximumCardiacOutput(L/min/m2)|
|None to mild||A||>20||>14||>8|
|Mild to moderate||B||16-20||11-14||6-8|
|Moderate to severe||C||10-15||8-11||4-6|
Figure 1. Changes in pulmonary gas exchange data and calculated variables from a normal individual, and patients with COPD and CHF respectively, studied in our laboratory. Changes in oxygen consumption (Voj), CO, production (VcoJ, minute ventilation (Ve), oxygen pulse and dead space to tidal volume ratio (Vd /Vt) are plotted against increasing work rate on a treadmill. The normal individual was exercised using a three minute incremental protocol on the treadmill. The two impaired individuals were studied using a modified incremental protocol on the treadmill. Stages 1 and 2 are comparable workloads for both protocols.