Evaluation of Exercise Capacity Using Submaximal Exercise at a Constant Work Rate in Patients With Cardiovascular Disease
Background Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient’s daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (V̇o2) kinetics, we measured the time constant of V̇o2 both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects.
Methods and Results A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. V̇o2 was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of V̇o2 during the onset of 50-W exercise was 61.4±15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of V̇o2 were slower) than that in normal subjects (48.8±10.4 seconds, P=.008). The time constant of V̇o2 during the onset of exercise was significantly negatively correlated with peak V̇o2 (r=−.67) and maximal work rate (r=−.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak V̇o2 (r=−.63) and maximum work rate (r=−.54).
Conclusions The time constant of V̇o2 during and after recovery from 50 W of constant work rate exercise, which does not require the subject’s maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease.
Symptom-limited incremental exercise tests have long been used to estimate the severity of cardiovascular disease and the patient’s daily activity.1 2 3 4 Oxygen uptake (V̇o2) at maximal exercise (peak V̇o2) is a noninvasive parameter of cardiac reserve. However, data obtained at maximal exercise may not be reproducible5 because of factors such as the subject’s motivation and the criteria used by the physician to terminate the exercise test. Thus, cardiologists are interested in obtaining objective information based on submaximal rather than maximal exercise.4 6
While at the onset of exercise the oxygen requirement of muscle increases approximately exponentially, only a small amount of oxygen is available from intracellular sources.7 Since the ability to rapidly increase the delivery of oxygen is essential for cellular homeostasis, the ability to match the V̇o2 to the cellular oxygen requirement depends on cardiac and circulatory function. Thus, patients with cardiovascular disease may have a lower uptake of oxygen (a slowing of V̇o2 kinetics) at the onset of exercise as compared with normal subjects.
We hypothesized that a decrease in maximal exercise capacity can be estimated from V̇o2 kinetics at the onset of exercise. We therefore measured the time constant of V̇o2 during the onset of 50 W of constant work rate exercise and compared it with data obtained during maximal exercise in incremental exercise testing conducted in patients with a variety of cardiovascular diseases and in normal subjects. We also compared the time constant of V̇o2 during recovery from 50 W of constant work rate exercise with data on exercise capacity in these subjects.
Thirty-four consecutive patients with cardiovascular disease classified as New York Heart Association functional class I or II were studied between May 1992 and August 1993 (Table 1⇓). Fourteen healthy subjects who were recruited from a medical screening clinic during this period and determined to be free of any significant disease on the basis of history, physical examination, chest radiograph, 12-lead ECG, and other routine laboratory tests were also studied (Table 1⇓). These 14 subjects had a normal ECG response on a screening maximal ergometer exercise. Diagnoses of the patients included previous myocardial infarction (13 patients), coronary artery disease without myocardial infarction (7 patients), valvular heart disease (6 patients), dilated cardiomyopathy (5 patients), hypertensive heart disease (1 patient), and other heart disease (2 patients). We excluded from the study those with pure mitral stenosis, aortic stenosis, unstable angina, heart failure classified as functional class III or IV, and documented lung disease. No patient had a myocardial infarction within the month before enrollment in the study. All patients were clinically stable at the time of the study. A β-blocker was withheld for 7 days. A slow-release nitrate or calcium antagonist was withheld for 48 hours. All the other medications were withheld for at least 24 hours before the study. The nature and purpose of the study was explained to the subjects, and after being so informed, each consented voluntarily to participate in the study.
An upright, electromagnetically braked cycle ergometer (Siemens-Elema 930, Siemens Elema AB) was used in the exercise test. On the day of the study, each subject performed the 50-W constant work rate test for 6 minutes starting from rest and then performed an incremental exercise test to the symptom-limited maximum. The incremental exercise test began with a 3-minute warm-up at 20 W and 60 rpm; the load then was increased incrementally by 1 W every 6 seconds. The interval between the two tests was approximately 60 minutes. A 12-lead ECG was obtained every minute using a Case II Stress System (Marquette Electronics). Cuff blood pressure was determined every minute with an automatic indirect manometer (STBP-680F, Collin Denshi). The end point of the incremental exercise test was chest pain in 3 patients who had coronary artery disease; it was leg fatigue or dyspnea in the remaining subjects.
Measurements of V̇o2 During Exercise
V̇o2 was measured with the subject at rest, seated on the ergometer, and throughout the exercise period, using an Aeromonitor AE-280 (Minato Medical Science).8 This system consists of a microcomputer, a hot-wire flowmeter, and oxygen and carbon dioxide gas analyzers (zirconium element–based oxygen analyzer and infra-red carbon dioxide analyzer). Gas was sampled at the rate of 220 mL/min through a filter by a suction pump through the analyzers. The Aeromonitor AE-280 calculated the breath-by-breath V̇o2 based on the mathematical analysis described by Beaver et al.9 The system was calibrated before each study.
Resting V̇o2 was determined as the average of 2 minutes with the subject sitting on the ergometer before starting exercise. The V̇o2 at 6 minutes was determined as the average between 330 to 360 seconds during 50-W exercise. Peak V̇o2 was defined as the highest V̇o2 that was attained over a 10-second period during incremental exercise.
A five-point moving average of the breath-by-breath data was used to evaluate V̇o2 kinetics during the 50-W constant work rate exercise. The time constant of V̇o2 kinetics was determined by fitting a monoexponential function to the V̇o2 response starting at exercise onset, assuming the resting value of V̇o2 as its baseline.10 11 The time constant was derived by nonlinear regression by using least-squares and iterative techniques10 11 with a bmdp statistical software package.12 The time constant of V̇o2 during recovery from the 50-W exercise was determined similarly in all subjects except for subject 17 (Table 1⇑), whose respiratory gases could not be obtained during recovery.
Data are reported as mean±SD. Comparisons of variables between normal subjects and patients with cardiovascular disease were made by unpaired t tests. The comparison of the time constant of V̇o2 during exercise with that of recovery was made by paired t tests. Linear regression analysis was used to correlate the time constant of V̇o2 and other variables. Differences were considered statistically significant at P<.05.
Table 2⇓ shows the mean maximum work rate and the peak V̇o2 as determined in the incremental exercise tests in the cardiac patients and in the normal subjects. Differences in both variables between the two groups were statistically significant.
Fig 1⇓ shows the changes in V̇o2 during 50 W of constant work rate exercise and during recovery, along with the computer-derived line of the best fit to a single exponential model of the V̇o2 response, for a representative normal subject (subject 5 in Table 1⇑). After the onset of exercise, V̇o2 increased exponentially and reached a steady state within approximately 3 minutes of exercise in the normal subject. The kinetics of V̇o2 during recovery from exercise were similar to that during exercise; the calculated time constants of V̇o2 during exercise and recovery were 39.9 and 39.7 seconds, respectively.
The time constant of V̇o2 response during 50 W of exercise was determined in all subjects. The kinetics of V̇o2 during exercise tended to be slower in the patients with cardiovascular disease, showing a significantly longer time constant as compared with the normal subjects (61.4±15.2 versus 48.8±10.4 seconds, P=.008). The mean time constant during recovery also was significantly longer in the patients with cardiovascular disease than that of normal subjects (58.7±12.6 versus 49.4±11.7 seconds, P=.02).
The relation between the time constant of V̇o2 during 50-W exercise and the parameters for exercise capacity obtained during incremental exercise testing appears for all subjects in Fig 2⇓. The time constant of V̇o2 increased with a decrease in peak V̇o2, with a significant negative correlation observed between the two variables (r=−.67). There also was a significant negative correlation between the time constant of V̇o2 and the maximum work rate (r=−.66). Similarly, the time constant of V̇o2 during recovery showed a significant negative correlation with the peak V̇o2 (r=−.63) and the maximum work rate (r=−.54) in all subjects (Fig 3⇓).
Even in the patient population excluding normal subjects, the time constant of V̇o2 during 50-W exercise showed a significant negative correlation with peak V̇o2 (r=−.57) and the maximum work rate (r=−.59). The time constant of V̇o2 during recovery from 50-W exercise also showed a significant negative correlation with peak V̇o2 (r=−.56) and the maximum work rate (r=−.40) in this population.
The time constant of V̇o2 during exercise at 50 W of constant work rate and that of recovery showed a significant positive correlation (r=.53) (Fig 4⇓). The difference between the time constant of V̇o2 during exercise and that of recovery was not significant by the paired t test.
The time constant of V̇o2 during exercise became longer with age in normal subjects (y=0.50x+26.8, r=.71); the time constant of V̇o2 during recovery also tended to be longer with age (y=0.33x+34.8, r=.42).
The V̇o2 response during constant work rate exercise is postulated to have three phases13 : phase I, an immediate increase at the start of exercise lasting approximately 20 seconds; phase II, a subsequent exponential increase that lasts 2 to 3 minutes; and phase III, a steady-state level or slow drift phase that starts at approximately 3 minutes. If the exercise at a constant work rate is mild or moderate, V̇o2 usually reaches a steady state within 3 minutes. However, at work rates associated with increased blood lactate, V̇o2 continues to increase beyond 3 minutes. Although we did not measure the blood lactate concentration, the time constant of V̇o2 is positively correlated with blood lactate level during exercise.11
If the work rate is sufficiently high, the phase I increase in V̇o2 is relatively small. The overall increase in V̇o2 during constant work rate exercise is determined mainly by increases in phase II and phase III. However, if the work rate is very low (15 or 20 W), the total V̇o2 increase during 6 minutes of exercise is determined mainly by the increase in phase I within the first 20 seconds.10 In this case, the increase in V̇o2 during phase II is small, making it difficult to estimate V̇o2 kinetics during this period. From our experience,14 most patients with functional class I or II can comfortably sustain 50 W of constant work rate exercise for 6 minutes. We therefore used a constant work rate exercise of 50 W in all subjects studied. In some patients, 50 W may be too high to be sustained for 6 minutes, especially those with severe heart failure classified as functional class III or IV or severe myocardial ischemia. However, the mean heart rate in our patients at 6 minutes at 50-W exercise was not very high (116±25 beats per minute; Table 2⇑). We therefore believe that this exercise can be performed safely by most patients with cardiovascular disease.
We used a single exponential equation to characterize the overall kinetics of the increase in V̇o2. Although the slowed V̇o2 kinetics seen in cardiac patients may have been better fitted to a double exponential equation,15 the methodology of this fitting would be too complex to obtain a clinical parameter for exercise capacity. However, a single exponential model is reported to characterize the increase in V̇o2 even during exercise associated with an increase in blood lactate.11 The V̇o2 during recovery from exercise is also known to decrease exponentially.16 Therefore, we used the same exponential model for the decreasing V̇o2 kinetics during recovery.
An oxygen deficit is defined as the difference between the predicted amount of oxygen required to perform the exercise (steady-state V̇o2×duration of exercise) and the actual cumulative consumption of oxygen.17 Oxygen debt is the difference between that consumed during recovery and the product of the preexercise resting V̇o2 and the duration of recovery.17 The oxygen deficit can be accounted for by existing chemical energy stores in the muscle as well as in tissue and blood, and, ultimately, the formation of ATP by the nonoxidative metabolism of carbohydrate substrates.7 10 18 The oxygen deficit and oxygen debt will be equal if the duration of exercise is long enough for the V̇o2 to reach a steady state.19 The time constant of V̇o2 during exercise and recovery can be calculated from the following equations.20 21
Therefore, if the work rate is moderate and the duration of exercise and recovery are long enough to reach a steady state, the time constant of V̇o2 during recovery would theoretically be identical to that of exercise, as we noted in this study.
The time constants of V̇o2 during exercise and recovery were both significantly prolonged in patients with cardiovascular disease as compared with normal subjects despite our finding of no difference in hemodynamic variables either at rest or at 6 minutes of exercise (Table 2⇑). Hughson and Smyth22 and Petersen et al23 reported that β-blockade slows the V̇o2 increase during submaximal exercise in normal subjects. Sietsema et al24 demonstrated that patients with cyanotic congenital heart disease exhibited prolonged V̇o2 response kinetics. The V̇o2 response also has been slowed by experimentally decreasing the blood oxygen content in normal subjects.11 These previous findings are consistent with our observations, although the normal subjects of the present study were not age-matched with the patients, and the time constant of V̇o2 was found to be influenced by age.
Because the pulmonary V̇o2 kinetics closely reflect muscular V̇o2 during the onset of constant work rate exercise, the slowed pulmonary V̇o2 kinetics probably are due to a decrease in oxygen availability at the exercising muscles. Therefore, the longer time constant of V̇o2 during exercise seen in cardiac patients with decreased exercise capacity must partly be related to their slower increase in cardiac output, as recently reported.25 26 Although the mechanism underlying V̇o2 kinetics during recovery is not well understood, the time course of cardiac output during recovery, which probably is slower in patients with cardiovascular disease,27 might have influenced recovery V̇o2 kinetics. However, the V̇o2 kinetics also are related to peripheral oxygen delivery and metabolic utilization at the exercising muscles. Therefore, the abnormal V̇o2 kinetics may not be specific for cardiovascular disease.
Maximal V̇o2, a plateau of V̇o2 despite further increases in the work rate, has been used as a useful parameter to evaluate maximal exercise capacity. Although maximal V̇o2 is generally determined by maximal cardiac output and the potential for oxygen extraction by the exercising muscles,13 28 this parameter is often difficult to obtain in patients with cardiovascular disease because of limitations such as chest pain or leg discomfort before attaining the target work rate. On the other hand, peak V̇o2, which is simply the highest V̇o2 attained during the incremental exercise, is easily influenced by the patient’s willingness to exercise as well as the subjective evaluation of the physician who has the responsibility to terminate the exercise test.
In patients with coronary artery disease, maximal exercise capacity may be artificially limited due to onset of angina, which may not be present at submaximal levels. Thus, there is a considerable amount of interest in obtaining objective and submaximal measurements of aerobic function. The time constant of V̇o2 during the initiation and recovery from the submaximal exercise is independent from maximal exercise effort and may be a better reflection of exercise limitations at a daily activity level compared with the maximal or peak V̇o2.
The present study used a Siemens Elema 930 ergometer, which requires approximately 10 seconds to reach the established work rate after the start of exercise. Therefore, the actual work rate was less than 50 W in the first 10 seconds. The characteristics of the work rate at the start of exercise may have influenced the phase I increase in V̇o2 and partly affected the calculated time constant of V̇o2. This influence would be more marked at a very low work rate, in which the magnitude of the increase in V̇o2 during the 6 minutes of exercise is determined mainly during the first 20 seconds. However, these characteristics did not affect the time constant of V̇o2 during recovery.
The time constants of V̇o2 during both the initiation of and the recovery from exercise showed significant negative correlations with peak V̇o2 and maximal work rate over a wide range of exercise capacity in our subjects. Although the factors that determine V̇o2 kinetics, especially during the recovery from exercise, remain to be clarified, we believe that the time constant of V̇o2 both during 50 W of constant work rate exercise and during recovery from this exercise, which does not require the subject’s maximal effort, is a useful parameter for objectively evaluating the exercise capacity of patients with mild to moderate cardiovascular disease.
Presented in part at the annual meeting of Experimental Biology, Anaheim, Calif, April 1994.
- Received August 12, 1994.
- Revision received September 22, 1994.
- Accepted October 26, 1994.
- Copyright © 1995 by American Heart Association
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