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(Chest. 2002;121:1581-1588.)
© 2002 American College of Chest Physicians

Prognostic Power of Ventilatory Responses During Submaximal Exercise in Patients With Chronic Heart Disease*

Akira Koike, MD; Haruki Itoh, MD; Makoto Kato, MD; Hitoshi Sawada, MD; Tadanori Aizawa, MD; Long Tai Fu, MD and Hiroshi Watanabe, MD

* From The Cardiovascular Institute, Tokyo, Japan.

Correspondence to: Akira Koike, MD, The Cardiovascular Institute, 3–10, Roppongi 7-chome, Minato-ku, Tokyo 106-0032, Japan; e-mail: koike{at}cepp.ne.jp


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Background: Although parameters obtained during submaximal exercise are known to be useful for predicting mortality in cardiac patients, it has been a matter of debate whether the submaximal parameters are superior to peak oxygen uptake (O2). For this purpose, we aimed to determine the best index among exercise variables in predicting long-term mortality in patients with chronic heart disease.

Methods: The study population consisted of 385 consecutive patients with chronic heart disease who performed a symptom-limited incremental exercise test on a cycle ergometer. Breath-by-breath respiratory gas analysis was used to estimate the peak O2, the ratio of the increase in O2 to the increase in work rate (WR) [O2/{Delta}WR], and the ratio of the increase in minute ventilation E to the increase in carbon dioxide output (CO2) [{Delta}E/{Delta}CO2].

Results: After 1,899 ± 495 days of follow-up (mean ± SD), 33 cardiovascular-related deaths occurred. Nonsurvivors achieved lower peak O2, lower O2/{Delta}WR, and higher {Delta}E/{Delta}CO2 compared to the survivors. In the univariate Cox proportional hazards analysis, peak O2, O2/{Delta}WR, and {Delta}E/{Delta}CO2 were found to be significant prognostic indexes of survival. However, multivariate analysis revealed O2/{Delta}WR as an independent predictor of mortality and {Delta}E/{delta}CO2 as a slightly weaker predictor. In this analysis, the prognostic power of peak O2 was insignificant.

Conclusion: Submaximal respiratory gas indexes are very likely to be more sensitive than peak O2 for predicting poor survival in ambulatory patients with chronic heart disease.

Key Words: cardiac patient • oxygen uptake • prognosis • ventilation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Parameters obtained from cardiopulmonary exercise testing such as the peak oxygen uptake (O2), gas exchange (anaerobic) threshold, and ratio of the increase in O2 to the increase in work rate (WR) [{Delta}O2/{Delta}WR] reflect the severity of heart disease and the activities of daily living in cardiac patients.1 2 3 4 5 6 7 8 Among these, peak O2 has traditionally been considered a "gold standard" for identifying patients with poor prognosis and selecting candidates for cardiac transplantation.9 10 11 12 However, the measurement of peak O2 depends on the subject’s motivation and is easily influenced by the bias of the investigator. Thus, there is a considerable interest among cardiologists in obtaining exercise parameters from submaximal rather than maximal exercise testing.

Chua et al13 examined the relation between ventilatory response during a symptom-limited exercise and mortality over a 2-year follow-up period in cardiac patients. In their study, the ratio of the increase in minute ventilation (E) to the increase in carbon dioxide output (CO2) during graded exercise ({Delta}E/{Delta}CO2) rose in parallel with the severity of the heart failure experienced. They also found that the {Delta}E/{Delta}CO2 ratio is an independent prognostic marker in these patients.

Parameters obtained during submaximal exercise have an advantage over peak O2 in that they can be obtained without maximal effort. While peak O2 depends simply on the value attained during a short period of time, {Delta}E/{Delta}CO2 and {Delta}O2/{Delta}WR are characterized by the time courses of respiratory gas variables7 14 that reflect the adaptive capacity of cardiopulmonary function to the increasing WR. Thus, the submaximal parameters may be more sensitive than peak O2 in predicting mortality in cardiac patients. However, it is still a matter of debate whether the parameters obtained during submaximal exercise are superior to peak O2.

In the present study, we measured peak O2, the gas exchange threshold, {Delta}O2/{Delta}WR, and {Delta}E/CO2 in patients with chronic heart disease, and then we evaluated the relation between these indexes and the patients’ mortality. We sought to determine the best index among the cardiopulmonary variables obtained from incremental exercise in predicting long-term mortality in patients with chronic heart disease.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Study Patients
We retrospectively studied 439 consecutive patients with cardiovascular disease who performed exercise testing with respiratory gas analysis between January 1992 and December 1994. The exercise testing was performed to evaluate the exercise capacity or cause of dyspnea. A patient with documented lung disease was not included in this population. The protocol and procedures for the exercise testing were approved by the human subjects committee of the institution. Its purposes and risks were explained to the patients, and informed consent was obtained from each patient.

Data on mortality were examined in July 1999 by examining medical records from the outpatient clinic and/or conducting telephone interviews with the patients or their families. Data on 45 patients were not available for follow-up due to changes in their place of residence. Nine patients died of noncardiovascular-related diseases during the follow-up period. After excluding these 54 patients, data on the remaining 385 patients were used for analysis (Table 1 ). Our study focused on mortality due to any cardiovascular-related diseases.


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  		Table 1. Clinical Characteristics of Patients With Cardiovascular Disease*

 
Coronary artery disease was diagnosed by a presence of significant coronary stenosis defined as >= 75% reduction in luminal diameter of coronary vessels or a presence of myocardial infarction diagnosed according to the World Health Organization criteria.15 Among 186 patients who were categorized as having coronary artery disease (Table 1) , 115 patients had previous myocardial infarction. Hypertensive heart disease (n = 23) was defined by echocardiography when left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] < 60%) and/or hypertrophy (thickness of the interventricular septum or posterior wall >= 12 mm) coexisted with hypertension. Patients who had cardiac arrhythmias requiring antiarrhythmic agents (n = 14), cardiac tumors (n = 5), and primary pulmonary hypertension (n = 1) were categorized as having "other" heart disease.

Cardiopulmonary Exercise Testing
An incremental symptom-limited exercise test was performed using an upright, electromagnetically-braked cycle ergometer (Corival 400; Lode; Groningen, the Netherlands). Breath-by-breath O2, CO2, and E were measured throughout the test using an AE-280 Respiromonitor (Minato Medical Science; Osaka, Japan).16 17 Exercise began with a 4-min warm-up at 10 W or 20 W at 60 revolutions per minute, and the load was increased incrementally by 1 W every 6 s (10 W/min). The WR of warm-up exercise was selected as 10 W in 25 patients whose daily activity was assumed to be very low. In the remaining 360 patients, 20 W was used.

Data Analysis
Prior to calculation of the parameters from respiratory gas analysis, a 5-point moving average of the breath-by-breath data was performed. The gas exchange threshold was determined by the V-slope method.18 19 20 {Delta}O2/{Delta}WR was calculated by least-squares linear regression from the data recorded between 30 s after the start of incremental exercise to 30 s before the end of exercise. {Delta}O2/{Delta}WR was not calculated in 38 subjects whose period of incremental exercise was < 2 min because of insufficient data points.

{Delta}E/{Delta}CO2 was calculated from the start of incremental exercise to the respiratory compensation point by the least-squares linear regression. The respiratory compensation point was determined by the following criteria21 : (1) the ratio of E to CO2 starts to increase after a period of decrease or stasis, and (2) the end-tidal PCO2 starts to decrease after a period of stasis. When the respiratory compensation point could not be clearly identified, {Delta}E/{Delta}CO2 was calculated from the data recorded between the start of incremental exercise to the end of the exercise. LVEF was calculated by echocardiography, which was performed routinely at a resting condition at an interval of 9 ± 14 days from exercise testing.

Statistics
Data are presented as the mean ± SD. Intergroup differences for variables were compared using the unpaired t test or {chi}2 analysis, where appropriate. A Cox proportional hazards model was used to measure the impact of cardiopulmonary variables on survival time. A multivariate Cox proportional hazards analysis was performed only in the subjects who had all the variables entered in the analysis. Any subject with a missing value was excluded from this analysis. Differences in survival between groups were detected by the Kaplan-Meier method and compared using the log-rank test. For all comparisons, p < 0.05 was considered statistically significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
No patient underwent cardiac transplantation or implantation of a cardioverter-defibrillator during the follow-up period (1,899 ± 495 days). However, among 186 patients with coronary artery disease, 53 patients received percutaneous coronary intervention and 19 patients underwent coronary artery bypass graft surgery during the follow-up period. Among 113 patients with valvular disease, 38 patients underwent replacements and/or repairs of cardiac valves during the period. In 6 of 20 patients who had congenital heart disease, a cardiac operation was performed to repair the disease during the follow-up period.

After 1,899 ± 495 days of follow-up, 33 cardiovascular-related deaths occurred. Of these, 13 patients died of progressive heart failure, 10 patients had a sudden cardiac death, 6 patients died of acute myocardial infarction, and 4 patients died of cerebrovascular diseases. Table 1 shows a comparison of clinical characteristics between survivors and nonsurvivors. There were no significant differences between survivors and nonsurvivors in the etiology of heart disease or in any of the prescribed medications except for the diuretics. The mean age of the nonsurvivors was 64.1 ± 9.5 years at the time of the exercise testing, which was significantly higher than that of the survivors (57.8 ± 10.0 years).

While peak O2 was determined in all the patients, the gas exchange threshold could not be determined in 50 patients. {Delta}O2/{Delta}WR was not obtained in 43 patients because of insufficient exercise duration (n = 38) or random noise of respiratory gas data that was considered inappropriate to apply a linear regression analysis (n = 5). {Delta}E/{Delta}CO2 could not be calculated in 16 patients because of insufficient data points (n = 11) or random noise of the data (n = 5).

Nonsurvivors achieved lower peak O2 than survivors (13.9 ± 3.8 mL/min/kg vs 15.9 ± 4.4 mL/min/kg, respectively). {Delta}O2/{Delta}WR in nonsurvivors was 6.5 ± 2.1 mL/min/W, which was significantly lower than that in survivors (8.4 ± 2.2 mL/min/W). {Delta}E/{Delta}CO2 was significantly higher in nonsurvivors than in survivors (41.1 ± 12.4 vs 33.1 ± 8.4, respectively). Echocardiography was obtained in 347 of 385 patients. LVEF at rest was 46.4 ± 19.4% in nonsurvivors, which was lower than that of survivors (60.1 ± 15.4%).

Table 2 shows a univariate Cox proportional hazards analysis of the association between cardiopulmonary indexes and survival time. Among exercise variables, {Delta}E/{Delta}CO2, {Delta}O2/{Delta}WR, and peak O2 were found to be significant prognostic indexes of survival. Also, LVEF was found to be a significant prognostic index. Table 3 shows the multivariate Cox proportional hazards analysis for {Delta}E/{Delta}CO2, {Delta}O2/{Delta}WR, and peak O2. When these three indexes were entered all together as continuous variables (model 1), {Delta}O2/{Delta}WR (p = 0.039) was a independent predictor of mortality, and {Delta}E/{Delta}CO2 was a slightly weaker predictor (p = 0.051). The prognostic power of peak O2 became insignificant when controlled by {Delta}O2/{Delta}WR and {Delta}E/{Delta}CO2. When LVEF was added to this analysis, only LVEF (p < 0.001) and {Delta}O2/{Delta}WR (p < 0.05) emerged as significant prognostic variables.


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  		Table 2. Univariate Cox Proportional Hazard Survival Analysis of Association Between Variables Studied and Survival Time

 

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  		Table 3. Multivariate Cox Proportional Hazard Survival Analysis of Association Between Respiratory Gas Variables and Survival Time

 
Figure 1 shows the Kaplan-Meier survival curves in each group of subjects classified on the basis of {Delta}O2/{Delta}WR: patients with {Delta}O2/{Delta}WR >= 9 (n = 132), those with {Delta}O2/{Delta}WR >= 7 to 9 (n = 109), and those with O2/{Delta}WR < 7 mL/min/W (n = 101). Kaplan-Meier survival curves for 2,500 days of follow-up demonstrated survival rates of 98.5%, 92.7%, and 84.2% for patients with {Delta}O2/{Delta}WR >= 9, >= 7 to 9, and < 7 mL/min/W, respectively. The difference in survival among the three groups was statistically significant (degrees of freedom [df] = 2, p = 0.0001), and also within each group. When LVEF was incorporated, a subgroup of the patients with {Delta}O2/{Delta}WR < 7 mL/min/W and LVEF < 50% (n = 24) had further worse prognosis (survival rate, 62.5%).



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  		Figure 1. Kaplan-Meier survival curves for patients stratified into three groups on the basis of {Delta}O2/{Delta}WR: patients with {Delta}O2/{Delta}WR >= 9 (n = 132), those with {Delta}O2/{Delta}WR >= 7 to 9 (n = 109), and those with {Delta}O2/{Delta}WR < 7 mL/min/W (n = 101). The difference in survival among three groups was statistically significant (df = 2, p = 0.0001), and also within each group. A Kaplan-Meier survival curve in a subgroup of the patients with {Delta}O2/{Delta}WR < 7 mL/min/W and LVEF < 50% (n = 24) is also shown by a thin line.

 
Figure 2 demonstrates Kaplan-Meier survival curves in the patients who were stratified into three groups on the basis of {Delta}E/{Delta}CO2: patients with {Delta}E/{Delta}CO2 < 30 (n = 134), those with {Delta}E/{Delta}CO2 >= 30 to 40 (n = 165), and those with {Delta}E/{Delta}CO2 >= 40 (n = 70). The survival rates were 95.5%, 93.9%, and 75.7% for patients with {Delta}E/{Delta}CO2 < 30, >= 30 to 40, and >= 40, respectively. The difference in survival among the three groups was statistically significant (df = 2, p < 0.0001). However, in the comparisons within each group, patients with {Delta}E/{Delta}CO2 >= 40 had a significantly worse prognosis than the other two groups; the difference in the prognosis between patients with {Delta}E/{Delta}CO2 < 30 and those with >= 30 to 40 was not significant. In the patients with {Delta}E/{Delta}CO2 >= 40 and LVEF < 50% (n = 25), the survival rate was decreased further to 56.0%.



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  		Figure 2. Kaplan-Meier survival curves for patients stratified into three groups on the basis of {Delta}E/VCO2: patients with {Delta}E/{Delta}CO2 < 30 (n = 134), those with {Delta}E/{Delta}CO2 >= 30 to 40 (n = 165), and those with {Delta}E/{Delta}CO2 >= 40 (n = 70). Patients with {Delta}E/{Delta}CO2 >= 40 had a significantly worse prognosis than those in the other two groups. A subgroup of the patients with {Delta}E/{Delta}CO2 >= 40 and LVEF < 50% (n = 25) had further worse prognosis.

 
Figure 3 shows the Kaplan-Meier survival curves in patients with peak O2 >= 14 mL/min/kg (n = 231) and those with peak O2 < 14 mL/min/kg (n = 154). The survival rate in the patients with higher peak O2, 94.4%, was significantly higher than that in those with lower peak O2, 87.0% (p = 0.005). When {Delta}O2/{Delta}WR, {Delta}E/{Delta}CO2, and peak O2 were considered as categorical variables in the multivariate analysis (model 2 in Table 3 ), the higher {Delta}E/{Delta}CO2 (>= 40) was an independent predictor of mortality and the lower {Delta}O2/{Delta}WR (< 7 mL/min/W) was a slightly weaker predictor. In this analysis, the lower peak O2 (< 14 mL/min/kg) was not an independent predictor of mortality.



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  		Figure 3. Kaplan-Meier survival curves for patients stratified on the basis of peak O2. Patients with peak O2 < 14 mL/min/kg had a worse prognosis than those with peak O2 >= 14 mL/min/kg.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Until recently, risk stratification of chronic heart disease was primarily based on the functional assessment and resting hemodynamic measurements.22 23 However, the former is subject to the physician’s bias, and the latter does not necessarily correlate with the clinical manifestations of heart failure.9 24 Hence, cardiopulmonary exercise testing is becoming important for stratifying cardiac patients2 4 and singling out those with poor prognosis.10 11 13 25 In 1991, Mancini et al9 proposed that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction when the peak O2 is > 14 mL/min/kg. Since then, peak O2 has been considered a key index to list for cardiac transplantation. The advantage of measuring peak O2 for predicting prognosis has also been reported by other investigators.10 11 25 26

In 1997, Chua et al13 found that patients with higher {Delta}E/{Delta}CO2 had a poor prognosis in a retrospective evaluation of 173 cardiac patients who performed treadmill cardiopulmonary exercise testing (96 patients with ischemic heart disease, 69 patients with dilated cardiomyopathy, and 8 patients with other cardiac diseases). They also suggested that the prognostic power of {Delta}E/{Delta}CO2 may be superior to that of peak O2. Robbins et al27 focused on the ratio of {Delta}E/{Delta}CO2 at peak exercise rather than the slope. They indicated that a high {Delta}E/{Delta}CO2 at peak exercise is a better predictor of mortality than low O2 at peak exercise.

Our present study confirms these previous findings and extends further in several important aspects. First, {Delta}O2/{Delta}WR during submaximal incremental exercise was newly identified as a strong independent predictor of mortality in patients with chronic heart disease. Second, the prognostic power of {Delta}O2/{Delta}WR and {Delta}E/{Delta}CO2 exceeds that of peak O2 in these patients. Third, as noted by Robbins et al27 for peak exercise {Delta}E/{Delta}CO2, {Delta}E/{Delta}CO2 revealed a threshold pattern as a prognostic index. Namely, a mild increase in {Delta}E/{Delta}CO230~40 is not related to a poor prognosis, while a {Delta}E/{Delta}CO2 > 40 is a strong prognostic index. Fourth, resting LVEF was unexpectedly found to be a strong predictor of mortality in patients with chronic heart disease.

Pardaens et al26 compared the prognostic power of submaximal respiratory data including {Delta}E/{Delta}CO2 with that of peak O2 in heart transplant candidates. Although respiratory gas variables during submaximal exercise were significant predictors of outcome, the prognostic power of peak O2 was superior to that of submaximal indexes. The discrepancy between their results and our present findings might be due in some part to the methodology used to determine {Delta}E/{Delta}CO2 and severity of heart disease of the enrolled subjects. They used a mixing chamber (not a breath-by-breath system) to analyze respiratory gases and calculated the slope of {Delta}E/{Delta}CO2 using the data from rest to a gas exchange ratio of 1.0, which is generally lower than the respiratory compensation point. Also, mean LVEF of their subjects was 26%, which was considerably lower than those of our subjects.

Clinical Implications of {Delta}O2/{Delta}WR
In healthy subjects, {Delta}O2/{Delta}WR is known to be approximately 10 mL/min/W.28 It has been reported that {Delta}O2/{Delta}WR positively correlates with peak O2 and becomes lower with the severity of heart disease.4 6 7 28 29 In patients with coronary artery disease, the lower slope of {Delta}O2/{Delta}WR is significantly related to the severity of coronary stenosis.30 O2/{Delta}WR is determined by the rate of the increase in cardiac output and the rate of difference of arterial-mixed venous oxygen during incremental exercise. Thus, a shallower slope of {Delta}O2/{Delta}WR can also be seen in patients with anemia and pulmonary vascular disease.20 21 The lower {Delta}O2/{Delta}WR in nonsurvivors strongly suggests an insufficient cardiac reserve and/or insufficient vasodilator capacity in the skeletal muscle in addition to the possible abnormalities in pulmonary vasculature. Impairment in the vasodilator capacity of the vascular smooth muscle would probably imply atherosclerosis or endothelial dysfunction in the systemic vasculature, including coronary and cerebral arteries. We speculate that for these reasons, a lower {Delta}O2/{Delta}WR could help single out the patients with lower survival due to myocardial infarction, cerebrovascular diseases, and progressive heart failure.

In the present study, {Delta}O2/{Delta}WR could not be calculated in 43 patients (36 survivors and 7 nonsurvivors), many of whom exercised for only a short duration. The WR of warm-up exercise was selected as 10 W in 25 subjects; in the remaining subjects, 20 W was used. For the purpose of determining {Delta}O2/{Delta}WR, even lower WR (such as 0 W) would be desirable for warm-up exercise, if a cycle ergometer could accurately generate this intensity. We used the same rate of the incremental exercise (10 W/min) in all the subjects. If the shallower slope of the incremental exercise (such as 5 W/min) was used in patients with lower exercise capacity, we could also increase our chances for determining exercise data with {Delta}O2/{Delta}WR by prolonging the exercise duration. However, {Delta}O2/{Delta}WR depends on the slope of the incremental exercise in itself.7 31 Thus, the same rate of increasing WR was necessary in all the subjects in the present study.

Clinical Implications of {Delta}E/{Delta}CO2
{Delta}E/{Delta}CO2 has been thought to range from approximately 24 to 34 in normal subjects.13 14 21 32 {Delta}E/{Delta}CO2 is known to be steeper in cardiac patients, according to the severity of heart failure.13 32 33 Theoretically, a steeper slope of {Delta}E/{Delta}VCO2 is assumed to relate to an increase in the pulmonary dead space to tidal volume ratio (VD/VT) or a decrease in the regulatory set point for PaCO2. Although we did not measure PaCO2 in the present study, it has been demonstrated that the degree of cardiac dysfunction does not significantly affect PaCO2 during exercise.34 Thus, the steeper slope of {Delta}E/{Delta}CO2 might be partly attributable to a higher VD/VT,33 34 especially in patients with heart failure. The increase in VD/VT in these patients is probably due to ventilation/perfusion mismatching, ie, reduced or absent perfusion in the well-ventilated lung.33 34 Although patients with documented lung disease were not included, spirometric measurements, such as resting FEV1 or vital capacity, were not made in all the subjects in the present study. Wasserman et al34 noted that FEV1 and vital capacity are proportionately reduced in cardiac patients according to the severity of heart disease, indicating the presence of lung restriction in these patients. Also, cardiac patients often have obstructive airways disease, since it has common risk factors with coronary artery disease (smoking). Thus, the elevated slope of {Delta}E/{Delta}CO2 in our patients with preserved left ventricular function might be attributed partly to the impairment in their lung function.

Another possible factor determining {Delta}E/{Delta}CO2 might be the blood lactate level during exercise. During incremental exercise, lactic acidosis develops. This development occurs at lower intensity exercise as the heart disease worsens. Bicarbonate is the primary buffer of lactic acid resulting in the increase in CO2, thereby causing higher ventilation. Weber and Janicki35 demonstrated that only submaximal anaerobic endurance exercise was associated with a nonsteady-state ventilatory response and this was related to an increase in mixed venous lactate concentration. Similarly, Janicki et al36 demonstrated that, in patients with pulmonary disease, the abnormal response in ventilation during incremental exercise could not be entirely explained by the increase in CO2. These findings, therefore, suggest that the excess in ventilation is related to the increase in blood lactate level itself. By these mechanisms determining the slope of {Delta}E/{Delta}CO2, higher {Delta}E/CO2 could probably lead to a worse prognosis.

Study Limitations
Parameters of cardiopulmonary exercise testing are known to integrate cardiac function, lung function, and oxygen delivery and utilization in exercising muscles. Although the prognostic power of the parameters may depend, in some part, on the etiology of heart disease, the number of the subjects of the present study was not sufficient to bring out disease-specific characteristics of each prognostic index. Of 33 deaths, only 13 deaths were due to progressive heart failure in the present study. We assume that {Delta}O2/{Delta}WR could help predict worse prognosis due to the other types of events (such as acute myocardial infarction or cerebrovascular diseases) because {Delta}O2/{Delta}WR is probably related to the vasomotor abnormalities in the systemic vasculature. However, it is not clearly understood why {Delta}E/{Delta}CO2 was associated with these events.

In the present study, 45 patients (10% of the total population) were not available for follow-up. Although we do not believe that these dropout patients significantly affected the present findings, a prospective study of a large cohort of patients will be necessary to establish a precise definition for selecting patients with poor prognosis by indexes of cardiopulmonary exercise testing.

The results of our present study do not refute the significance of peak O2 in predicting mortality in heart failure patients and in selecting candidates for cardiac transplantation, since the prognostic power of indexes obtained during cardiopulmonary exercise testing also depends on the severity of heart disease. It will be desirable to estimate cardiac reserve and to identify high-risk ambulatory patients by integrating the indexes of cardiopulmonary variables.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Among respiratory gas variables during incremental bicycle exercise, {Delta}O2/{Delta}WR and {Delta}E/{Delta}CO2 were found to be strong predictors of mortality in ambulatory patients with chronic heart disease, and peak O2 was found to be a relatively weak predictor. The prognostic power of {Delta}O2/{Delta}WR and {Delta}E/{Delta}CO2 became stronger by incorporating LVEF measured at rest. Submaximal respiratory gas indexes might be more sensitive than peak O2 for predicting poor survival in these patients.


   Acknowledgements
 
We thank Hiroyuki Iinuma, MD; Naohiko Osada, MD; Naomi Harada, BS; Osamu Nagayama, BS; Reiko Oohara, BS; Tomoko Maeda, BS; and Akihiko Tajima, BS, of The Cardiovascular Institute.


   Footnotes
 
Abbreviations: df = degrees of freedom; LVEF = left ventricular ejection fraction; CO2 = carbon dioxide output; VD/VT = pulmonary dead space to tidal volume ratio; E = minute ventilation; O2 = oxygen uptake; WR = work rate

Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and by the Research Grant for Cardiovascular Diseases from the Ministry of Health and Welfare.

Received for publication June 21, 2001. Accepted for publication October 28, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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