scholarly journals Reference Values and Predictive Equations for Cardiopulmonary Exercise Testing in Thai Adults

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Prapaporn Pornsuriyasak ◽  
Kitipong Ngaojaruwong ◽  
Suchada Saovieng ◽  
Jayanton Patumanond ◽  
Khanat Kruthkul ◽  
...  
Keyword(s):  
Physical Activity ◽  
Exercise Testing ◽  
Minute Ventilation ◽  
Cardiopulmonary Exercise Testing ◽  
Activity Level ◽  
Screening Tests ◽  
Peak Exercise ◽  
Predictive Equations ◽  
Cardiopulmonary Exercise ◽  
History Of

Background: A series of racial specific predictive equations for exercise parameters are needed to determine a lack of cardiopulmonary fitness or having an exercise limitation on cardiopulmonary exercise testing (CPET). Objectives: The study aimed to develop a new set of predictive equations of CPET parameters during maximal cycling exercise for Thai adults. Methods: A sample of 580 Thai adults whom could pass screening tests were asked to fill a health questionnaire and the Global Physical Activity questionnaire. Participants with history of symptomatic heart and pulmonary diseases, current smokers, history of smoking ≥ 10 pack-years, and abnormal spirometry were excluded. The CPET was performed using a cycle ergometer with an incremental symptom-limited protocol. Values of CPET parameters at the peak exercise (oxygen uptake [V̇O2], work rate, heart rate, oxygen pulse, and minute ventilation), lactic acidosis threshold, and ventilatory equivalents for oxygen and carbon dioxide were documented. Analyses were stratified using age and gender criterion. Predictive equations for CPET parameters were established using multivariable linear regression with age (A), weight (W), height (H), and physical activity level (Act) as independent variables. Results: A total of 493 participants (208 men and 285 women) were analysed. The predictive equation of V̇O2peak (L.min-1) for males was: -2.268 + (0.037 × A) - (0.0005 × A2) + (0.016 × W) + (0.014 × H) + (0.104 × Act), (R2 = 0.41, SEE = 0.392), and for females, it was: -0.34 + (0.009 × A) - (0.0002 × A2) + (0.012 × W) + (0.005 × H) + (0.058 × Act), (R2 = 0.44, SEE = 0.220). Conclusions: This is the first study that constructed the predictive equations for cycling CPET parameters in Thai adults. These equations are useful to evaluate the cardiopulmonary health of the Thai population and may be generalized to other populations with geographical or ethnic proximity to the Thai people.

Cardiopulmonary Exercise Testing in Combined Pulmonary Fibrosis and Emphysema

Respiration ◽  
2021 ◽  
pp. 369-377
Author(s):  
Michael Westhoff ◽  
Patric Litterst ◽  
Ralf Ewert
Keyword(s):  
Body Weight ◽  
Pulmonary Fibrosis ◽  
Sensitivity And Specificity ◽  
Exercise Testing ◽  
Cardiopulmonary Exercise Testing ◽  
Arterial Oxygen ◽  
Peak Exercise ◽  
Cutoff Value ◽  
Cardiopulmonary Exercise ◽  
Peak Vo2

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct entity among fibrosing lung diseases with a high risk for lung cancer and pulmonary hypertension (PH). Notably, concomitant PH was identified as a negative prognostic indicator that could help with early diagnosis to provide important information regarding prognosis. Objectives: The current study aimed to determine whether cardiopulmonary exercise testing (CPET) can be helpful in differentiating patients having CPFE with and without PH. Methods: Patients diagnosed with CPFE in 2 German cities (Hemer and Greifswald) over a period of 10 years were included herein. CPET parameters, such as peak oxygen uptake (peak VO2), functional dead space ventilation (VDf/VT), alveolar-arterial oxygen difference (AaDO2), arterial-end-tidal CO2 difference [P(a-ET)CO2] at peak exercise, and the minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), were compared between patients with and without PH. Results: A total of 41 patients with CPET (22 with PH, 19 without PH) were analyzed. Right heart catheterization was performed in 15 of 41 patients without clinically relevant complications. Significant differences in peak VO2 (861 ± 190 vs. 1,397 ± 439 mL), VO2/kg body weight/min (10.8 ± 2.6 vs. 17.4 ± 5.2 mL), peak AaDO2 (72.3 ± 7.3 vs. 46.3 ± 14.2 mm Hg), VE/VCO2 slope (70.1 ± 31.5 vs. 39.6 ± 9.6), and peak P(a-ET)tCO2 (13.9 ± 3.5 vs. 8.1 ± 3.6 mm Hg) were observed between patients with and without PH (p < 0.001). Patients with PH had significantly higher VDf/VT at rest, VT1, and at peak exercise (65.6 ± 16.8% vs. 47.2 ± 11.6%; p < 0.001) than those without PH. A cutoff value of 44 for VE/VCO2 slope had a sensitivity and specificity of 94.7 and 72.7%, while a cutoff value of 11 mm Hg for P(a-ET)CO2 in combination with peak AaDO2 >60 mm Hg had a specificity and sensitivity of 95.5 and 84.2%, respectively. Combining peak AaDO2 >60 mm Hg with peak VO2/body weight/min <16.5 mL/kg/min provided a sensitivity and specificity of 100 and 95.5%, respectively. Conclusion: This study provided initial data on CPET among patients having CPFE with and without PH. CPET can help noninvasively detect PH and identify patients at risk. AaDO2 at peak exercise, VE/VCO2 slope, peak P(a-ET)CO2, and peak VO2 were parameters that had high sensitivity and, when combined, high specificity.

scholarly journals Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Jones ◽  
Laura Tan ◽  
Suzanne Carey-Jones ◽  
Nathan Riddell ◽  
Richard Davies ◽  
...  
Keyword(s):  
Physical Activity ◽  
High Risk ◽  
Oxygen Uptake ◽  
Anaerobic Threshold ◽  
Exercise Testing ◽  
Low Cost ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Wearable Device ◽  
Cardiopulmonary Exercise

Abstract Background Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. Methods Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. Device selection Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. Results Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 males) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R = 0.57 (CI 0.29–0.76), R = 0.59 (CI 0.31–0.77) and R = 0.62 (CI 0.35–0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01–0.64), R = 0.39 (CI 0.04–0.66) and R = 0.42 (CI 0.07–0.68) respectively) and peak work (R = 0.56 (CI 0.27–0.75), R = 0.48 (CI 0.17–0.70) and R = 0.50 (CI 0.2–0.72) respectively). Receiver operator curve (ROC) analysis for direct and self-reported measures of 7-day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. Conclusions Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. Ethics This study entitled “uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)” gained favourable ethical opinion on 24 January 2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.

Abstract 13745: Severity of Functional Mitral Regurgitation During Maximal Exercise Testing in Heart Failure: Additional Value of Combining Echocardiography with Cardiopulmonary Exercise Testing

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Greta Generati ◽  
Francesco Bandera ◽  
Marta Pellegrino ◽  
Valentina Labate ◽  
Eleonora Alfonzetti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Exercise Testing ◽  
Cardiopulmonary Exercise Testing ◽  
Functional Mitral Regurgitation ◽  
Peak Exercise ◽  
Cardiopulmonary Exercise ◽  
Pulmonary Hemodynamic ◽  
Increased Risk

Background: In heart failure (HF) patients the severity of mitral regurgitation (MR) at rest has a well established prognostic value and its increase during exercise further adds to an increased risk. Our goal was to define the relationship between the degree of exercise MR severity with cardiopulmonary and echocardiographic related phenotypes in a cohort of HF patients. Methods: 71 HF reduced ejection fraction patients (mean age 67±11; male 72%; ischemic etiology 61%; NYHA class I, II, III and IV 13%, 36%, 39% and 12%, mean ejection fraction 33±9%) underwent cardiopulmonary exercise test (CPET) on tiltable cycle-ergometer combined with echocardiography at rest and during exercise. The population was divided into two groups according to the degree of functional peak MR: no to mild/moderate MR (no MR, MR1+ and MR2+) vs moderate/severe MR (MR3+ and MR4+). Results: A good correlation (ρ coefficient= 0.49) was found between the degree of dynamic MR and PASP at peak exercise. Despite similar echocardiographic profile at rest patients with significant peak MR (MR≥3+) had worse exercise performance (lower peak VO2, O2 pulse and workload) and impaired ventilatory efficiency (higher VE/VCO2 slope). Conclusions: In HF patients the severity of exercise-induced MR is associated with the most unfavorable performance and pulmonary hemodynamic response. A combined approach with CPET and echocardiographic assessment can help to early unmask and target functional MR and its related unfavorable phenotypes.

scholarly journals Exertional dyspnoea in COPD: the clinical utility of cardiopulmonary exercise testing

2016 ◽  
Vol 25 (141) ◽  
pp. 333-347 ◽  
Author(s):  
Denis E. O'Donnell ◽  
Amany F. Elbehairy ◽  
Azmy Faisal ◽  
Katherine A. Webb ◽  
J. Alberto Neder ◽  
...  
Keyword(s):  
Physical Activity ◽  
Exercise Testing ◽  
Physiological Responses ◽  
Cardiopulmonary Exercise Testing ◽  
Chronic Obstructive ◽  
Exertional Dyspnoea ◽  
Obstructive Pulmonary Disease ◽  
Respiratory Impairment ◽  
Laboratory Exercise ◽  
Cardiopulmonary Exercise

Activity-related dyspnoea is often the most distressing symptom experienced by patients with chronic obstructive pulmonary disease (COPD) and can persist despite comprehensive medical management. It is now clear that dyspnoea during physical activity occurs across the spectrum of disease severity, even in those with mild airway obstruction. Our understanding of the nature and source of dyspnoea is incomplete, but current aetiological concepts emphasise the importance of increased central neural drive to breathe in the setting of a reduced ability of the respiratory system to appropriately respond. Since dyspnoea is provoked or aggravated by physical activity, its concurrent measurement during standardised laboratory exercise testing is clearly important. Combining measurement of perceptual and physiological responses during exercise can provide valuable insights into symptom severity and its pathophysiological underpinnings. This review summarises the abnormal physiological responses to exercise in COPD, as these form the basis for modern constructs of the neurobiology of exertional dyspnoea. The main objectives are: 1) to examine the role of cardiopulmonary exercise testing (CPET) in uncovering the physiological mechanisms of exertional dyspnoea in patients with mild-to-moderate COPD; 2) to examine the escalating negative sensory consequences of progressive respiratory impairment with disease advancement; and 3) to build a physiological rationale for individualised treatment optimisation based on CPET.

scholarly journals Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery

2013 ◽  
Vol 95 (2) ◽  
pp. 125-130 ◽  
Author(s):  
LH Moyes ◽  
CJ McCaffer ◽  
RC Carter ◽  
GM Fullarton ◽  
CK Mackay ◽  
...  
Keyword(s):  
High Risk ◽  
Exercise Testing ◽  
Cardiopulmonary Exercise Testing ◽  
Major Surgery ◽  
Peak Exercise ◽  
Icu Admission ◽  
Cardiopulmonary Exercise ◽  
High Dependency ◽  
Cardiopulmonary Complications ◽  
Oesophagogastric Cancer

Introduction An anaerobic threshold (AT) of <11ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection. Methods Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38–84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality. Results The mean AT and VO2 peak were 10.8ml/min/kg (standard deviation [SD]: 2.8ml/min/kg, range: 4.6–19.3ml/min/kg) and 15.2ml/min/kg (SD: 5.3ml/min/kg, range: 5.4–33.3ml/min/kg) respectively; 57 patients (55%) had an AT of <11ml/min/ kg and 26 (12%) had an AT of <9ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9ml/min/kg compared with 29% of patients with an AT of ≥9ml/min/kg but <11ml/min/kg and 20% of patients with an AT of ≥11ml/min/kg (p=0.04). There was a trend that those with an AT of <11ml/min/kg and a low VO2 peak had a higher rate of unplanned ICU admission. Conclusions This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.

scholarly journals Ventilatory compensation during the incremental exercise test is inversely correlated with air trapping in COPD

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1661
Author(s):  
Rottem Kuint ◽  
Neville Berkman ◽  
Samir Nusair
Keyword(s):  
Gas Exchange ◽  
Exercise Testing ◽  
Exercise Test ◽  
Cardiopulmonary Exercise Testing ◽  
Incremental Exercise ◽  
Peak Exercise ◽  
Air Trapping ◽  
Incremental Exercise Test ◽  
Cardiopulmonary Exercise ◽  
Copd Patients

Background: Air trapping and gas exchange abnormalities are major causes of exercise limitation in chronic obstructive pulmonary disease (COPD). During incremental cardiopulmonary exercise testing, actual nadir values of ventilatory equivalents for carbon dioxide (V E/VCO 2) and oxygen (V E/VO 2) may be difficult to identify in COPD patients because of limited ventilatory compensation capacity. Therefore, we aimed in this exploratory study to detect a possible correlation between the magnitude of ventilation augmentation, as manifested by increments in ventilatory equivalents from nadir to peak exercise values and air trapping, detected with static testing.    Methods: In this observational study, we studied data obtained previously from 20 COPD patients who, during routine follow-up, underwent a symptom-limited incremental exercise test and in whom a plethysmography was obtained concurrently. Air trapping at rest was assessed by measurement of the residual volume (RV) to total lung capacity (TLC) ratio (RV/TLC). Gas exchange data collected during the symptom-limited incremental cardiopulmonary exercise test allowed determination of the nadir and peak exercise values of V E/VCO 2 and V E/VO 2, thus enabling calculation of the difference between peak exrcise value and nadir values of  V E/VCO 2 and V E/VO 2, designated ΔV E/VCO 2 and ΔV E/VO 2, respectively. Results: We found a statistically significant inverse correlation between both ΔV E/VCO 2 (r = -0. 5058, 95% CI -0.7750 to -0.08149, p = 0.0234) and ΔV E/VO 2 (r = -0.5588, 95% CI -0.8029 to -0.1545, p = 0.0104) and the degree of air trapping (RV/TLC). There was no correlation between ΔV E/VCO 2 and forced expiratory volume in the first second, or body mass index.  Conclusions: The ventilatory equivalents increment to compensate for acidosis during incremental exercise testing was inversely correlated with air trapping (RV/TLC).

Abstract 17232: Cardiopulmonary Exercise Testing in Diabetic Chronic Heart Failure Patients With Microalbuminuria

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Thida tabucanon ◽  
Timothy Engelman ◽  
Sanjeeb S Bhattacharya ◽  
J Emanuel Finet ◽  
Wai Hong W Tang
Keyword(s):  
Oxygen Consumption ◽  
Exercise Testing ◽  
Beta Blocker ◽  
Multivariable Analysis ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Peak Oxygen Consumption ◽  
Left Ventricular Ejection ◽  
Cardiopulmonary Exercise ◽  
History Of

Introduction: Microalbuminuria can be a presentation of microvascular complication in diabetes mellitus (DM). Hypothesis: Microalbuminuria is associated with impaired exercise performance in chronic HF with DM patients. Methods: We retrospectively analyzed a cardiopulmonary exercise testing (CPET) database in 255 chronic HF patients with DM that had urine microalbumin test between December 2012 and September 2019. Demographic data and CPET parameters were compared between the patients who had and had not microalbuminuria which was defined by microalbumin/creatinine ratio ≥ 30 mg/g. Peak oxygen consumption (peak VO 2 ) ≤ 14 ml/kg/min and ≤ 12 ml/kg/min if had history of beta-blocker uses were classified as low peak VO 2 and used in multivariable analysis. Results: There were a total 92 patients (36.1%) that had microalbuminuria. Mean age was not significant different between the patients with and without microalbuminuria (57.7 vs 59.4 years, p = 0.26). The patients with microalbuminuria had lower body mass index (BMI; 30.8 vs. 32.7 kg/m 2 , p = 0.014) and had more history of beta-blocker (BB) uses (81.5% vs. 69.3%, p = 0.038), no significant different in other medication uses. Left ventricular ejection fraction (LVEF) was significant lower in patients with microalbuminuria (35.8% vs. 41.5%, p = 0.028). The patients with microalbuminuria had significant higher prevalence of low peak VO 2 (45.7% vs. 30.1%, p = 0.015) and lower peak stroke work (VO 2 /HR; 11.5 vs. 12.8 ml/ beat, p = 0.008). No significant different in ventricular efficiency slope (VE/VCO 2 ; 37.1 vs. 35.4, p = 0.094), Multivariable analysis showed that proteinuria was independently associated with low peak VO 2 after adjusted for age, sex, BMI LVEF, history of BB uses, VE/VCO 2 and HR at peak VO 2 , (odds ratio = 3.83, p < 0.001). Conclusions: Microalbuminuria was independently associated with low peak oxygen consumption in chronic HF with DM patients.

Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing

2019 ◽  
Vol 40 (02) ◽  
pp. 125-132 ◽  
Author(s):  
Nduka Okwose ◽  
Jie Zhang ◽  
Shakir Chowdhury ◽  
David Houghton ◽  
Srdjan Ninkovic ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Exercise Testing ◽  
Coefficient Of Variation ◽  
Cardiopulmonary Exercise Testing ◽  
Exercise Stress ◽  
Inert Gas ◽  
Peak Exercise ◽  
Cardiopulmonary Exercise ◽  
Inert Gas Rebreathing ◽  
Rebreathing Method

AbstractThe present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23–32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min−1, p=0.54; 114 (28) vs. 108 (15) ml beat−1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (−1.1 to 1.8) liter min−1 and 0.5 (−2.3 to 3.3) liter min−1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.

scholarly journals The Role of Cardiopulmonary Exercise Test in IPF Prognosis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Christina Triantafillidou ◽  
Effrosyni Manali ◽  
Panagiotis Lyberopoulos ◽  
Likourgos Kolilekas ◽  
Konstantinos Kagouridis ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Exercise Testing ◽  
Risk Estimation ◽  
Minute Ventilation ◽  
Cardiopulmonary Exercise Testing ◽  
Lung Mechanics ◽  
Peak Oxygen Consumption ◽  
Exercise Limitation ◽  
Cardiopulmonary Exercise

Background. In IPF, defects in lung mechanics and gas exchange manifest with exercise limitation due to dyspnea, the most prominent and disabling symptom.Aim. To evaluate the role of exercise testing through the 6MWT (6-minute walk test) and CPET (cardiopulmonary exercise testing) in the survival of patients with IPF.Methods. This is a prospective, observational study evaluating in 25 patients the relationship between exercise variables through both the 6MWT and CPET and survival.Results. By the end of the observational period 17 patients were alive (33% mortality). Observation ranged from 9 to 64 months. VE/VCO2slope (slope of relation between minute ventilation and CO2production), VO2peak/kg (peak oxygen consumption/kg), VE/VCO2ratio at anaerobic threshold, 6MWT distance, desaturation, and DLCO% were significant predictors of survival while VE/VCO2slope and VO2peak/kg had the strongest correlation with outcome. The optimal model for mortality risk estimation was VO2peak/kg + DLCO% combined. Furthermore, VE/VCO2slope and VO2peak/kg were correlated with distance and desaturation during the 6MWT.Conclusion. The integration of oxygen consumption and diffusing capacity proved to be a reliable predictor of survival because both variables reflect major underlying physiologic determinants of exercise limitation.

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