Prognostic value of end-tidal carbon dioxide during exercise testing in heart failure
Introduction
Cardiopulmonary exercise testing (CPX) is commonly used to assess patients with heart failure (HF). Data obtained from CPX provides a wealth of diagnostic [1], [2] and prognostic [3], [4], [5] information in the HF population. Peak oxygen consumption (VO2) remains the most frequently applied CPX variable in both research and clinical settings [6]. Other variables, such as the relationship between minute ventilation (VE) and carbon dioxide production (VCO2), have also been demonstrated to have prognostic value in recent years [7], [8]. Given the wealth of information that can be gained from this assessment, further exploration of prognostically significant CPX variables is warranted.
The partial pressure of end-tidal carbon dioxide (PETCO2) is one such CPX variable that may possess prognostic value in the HF population. Matsumoto et al. [9] found that PETCO2 at the ventilatory threshold (VT) was significantly correlated with cardiac output at peak exercise in a group of subjects with HF. The sensitivity and specificity of PETCO2 (< 38.5 mm Hg) to predict a lower cardiac output during exercise (cardiac index < 5.11 l/min/m2 at peak exercise) were 76.5% and 75.0%, respectively. Tanabe et al. [10] likewise reported a significant correlation between PETCO2 and cardiac index at peak exercise in subjects diagnosed with HF. The results from these investigations indicate that PETCO2 closely reflects the cardiac output response to exercise and therefore may have diagnostic applications in patients with HF.
While there is evidence to demonstrate the diagnostic value of PETCO2 during exercise in HF, studies on prognosis are lacking. Our group has recently completed a study demonstrating that a lower PETCO2, obtained at rest, was a significant predictor of hospitalization/mortality in subjects with HF [11]. The purpose of the present study was to extend this analysis and examine the ability of PETCO2 during exercise to predict cardiac-related hospitalization and mortality in a group of patients with HF.
Section snippets
Methods
One hundred and thirty consecutive subjects diagnosed with HF underwent a symptom-limited CPX between 5/15/97 and 7/26/04 at Virginia Commonwealth University Medical Center. All tests were conducted on an outpatient basis and written informed consent was obtained from all subjects prior to testing. Virginia Commonwealth University Institutional Review Board approval was obtained for those subjects undergoing an exercise test as part of a prospective research project and not as a standard of
Equipment calibration
Ventilatory expired gas analysis was obtained using a metabolic cart (Medgraphics CPX-D, Minneapolis, MN or Sensormedics Vmax29, Yorba Linda, CA). The oxygen and carbon dioxide sensors were calibrated using gases with known oxygen, nitrogen, and carbon dioxide concentrations prior to each test. The flow sensor was also calibrated before each test using a 3-l syringe.
Testing procedure and data collection
Symptom-limited CPX was conducted using a treadmill. The modified ramping protocol selected for testing consisted of approximately 2 ml O2 kg− 1 min− 1 increases in workload every 30 s [13], [14], [15], [16]. Stage 1 began at 1.0 mile per hour (mph) and a 0% grade. Stages increased by 0.1 mph and 0.5% grade thereafter. Our group has found that this protocol minimizes the difference between estimated and measured VO2, indicating an acceptable kinetic response. Furthermore the gradual adjustment in
Data analysis
Oxygen consumption (ml kg− 1 min− 1), VCO2 (l/min) and VE (l/min) and PETCO2 were collected throughout the exercise test. Resting PETCO2 was also collected for 2 min prior to CPX in the seated position. Peak VO2 was expressed as the highest 10-s average value obtained during the last 30-s stage of the exercise test. The ventilatory equivalent method was used to determine PETCO2 at the ventilatory threshold (VT) [17]. Ten-second averaged VE and VCO2 data, from the initiation of exercise to peak,
Endpoints
Subjects were followed for cardiac-related mortality and hospitalization for 1 year following CPX via medical chart review. Cardiac-related mortality was defined as death directly resulting from failure of the cardiac system. An example fitting this definition is sudden cardiac death. Cardiac-related hospitalization was defined as a hospital admission directly resulting from cardiac dysfunction requiring in-patient care to correct. An example fitting this definition is decompensated HF
Statistical analysis
The mean and standard deviation were reported for key variables. Pearson product moment correlation was used to assess the relationship between measures of PETCO2 and age, LVEF, peak VO2 and the VE/CO2 slope. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of key resting and CPX continuous variables to predict cardiac-related events. For variables found to be statistically significant by ROC curve analysis, threshold values (highest combination of
Results
The primary reason for CPX termination was subject request secondary to volitional fatigue. No adverse events warranting premature test termination occurred. Mean values of CPX variables are listed in Table 2.
Pearson product moment correlation results are listed in Table 3. PETCO2 was significantly correlated with peak VO2 and the VE/VCO2 slope. PETCO2 at the VT was weakly correlated with age. None of the other PETCO2 variables were correlated with age or LVEF.
There were eight cardiac-related
Discussion
The results of the present study indicate that PETCO2 obtained during CPX has prognostic value in patients with HF. Specifically, the change in PETCO2 from rest to the VT, PETCO2 at the VT and PETCO2 at peak exercise were all significant predictors of outcome. These findings extend the diagnostic analyses performed by Matsumoto et al. [9] and Tanabe et al. [10], who both demonstrated changes in PETCO2 during CPX were significantly related to cardiac output and HF severity. In addition,
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