Research ArticleArticles

Metabolic Parameters Derived From Cardiopulmonary Stress Testing for Prediction of Prognosis in Patients With Heart Failure: The Ochsner Experience

Joaquin Crespo, Carl J. Lavie, Richard V. Milani, Yvonne E. Gilliland, Hamang M. Patel and Hector O. Ventura
Ochsner Journal June 2009, 9 (2) 46-53;

Abstract

Cardiopulmonary parameters, particularly peak oxygen consumption, have proven utility in prognostic stratification for patients with heart failure. These have been typically corrected for total body weight as opposed to lean body mass (LBM). For practical purposes, fat consumes virtually no oxygen and receives minimal perfusion. Based on this rationale and on observations from previous studies, several investigations conducted at the Ochsner Clinic Foundation have assessed the prognostic value of metabolic parameters when corrected for LBM. Three studies reviewed in this discussion consistently found greater prognostic value for LBM-corrected parameters, especially peak oxygen consumption and oxygen pulse. These findings lead to a strong recommendation for LBM correction of cardiopulmonary exercise stress test–derived parameters for more accurate prognostic stratification in patients with heart failure, especially in the obese population. Other centers have studied additional parameters such as the ventilation to carbon dioxide production slope, oxygen uptake efficiency slope, and partial pressure of end-tidal carbon dioxide during exercise and rest. In multiple studies, these ventilation-dependent parameters have shown prognostic superiority compared with the standard peak oxygen consumption even when obtained from submaximal exercise data. However, no study to our knowledge has compared these parameters with LBM-adjusted values as described herein. The prognostic validity of cardiopulmonary exercise stress test–derived parameters requires further investigation in patients treated with β-blockers.

INTRODUCTION

Exercise stress testing is commonly used in clinical practice to evaluate the presence and severity of coronary ischemia, as well as exertional symptoms, heart rate and blood pressure responses, and estimated aerobic capacity.1–3 By direct measurement of exercise respiratory gas exchange, cardiopulmonary exercise stress testing (CPX) adds important clinical information to that provided by the standard exercise stress test.1,4 In particular, CPX provides precise determination of aerobic capacity, the causes of dyspnea on exertion, and prognosis in patients with systolic heart failure (HF).1

The heart, lungs, and pulmonary and systemic circulations form a single circuit for exchange of respiratory gases between the environment and the cells of the body.1,5,6 Under steady-state conditions, oxygen consumption per unit time (Vo2) and carbon dioxide output (VCO2) measured at the mouth are equivalent to oxygen (O2) utilization and carbon dioxide production occurring in the cell; thus, external respiration equals internal respiration.1,6 CPX testing directly measures fractions of O2 and carbon dioxide in expired gas, expired air volume, or flow and calculates Vo2, VCO2, and minute ventilation (VE).1 Samples of expired air are typically assessed every 15 seconds, and real-time data are expressed in tabular and graphic formats.4 From these data, multiple metabolic parameters can be derived (Table 1). These parameters may be used for different diagnostic, therapeutic, and prognostic purposes (Table 2); risk stratification and prognosis in patients with systolic HF are most pertinent to this discussion.

View this table:
Table 1

Metabolic Parameters Measured or Derived From Cardiopulmonary Exercise Stress Testing (CPX)*

View this table:
Table 2

Potential Indications for Cardiopulmonary Stress Testing*

The application of CPX in categorizing the severity of HF has been described by many investigators such as Weber and Janicki in 1985.7 Subsequently, Szlachcic et al8 investigated the prognostic utility of CPX for HF and found a correlation between peak Vo2 and mortality. In the Veterans Administration Heart Failure Trial (v-HEFT),9 the mortality rate of patients with maximum oxygen consumption (Vo2max) not exceeding 14.5 mL/kg per minute was double that of patients whose Vo2max exceeded this value.1,4 In a separate investigation of patients with HF referred for heart transplantation (HT), Mancini et al10 found that peak Vo2 was the best single predictor of survival. Moreover, HT could be safely deferred in patients with peak Vo2 exceeding 14 mL/kg per minute, whose survival exceeded that of patients undergoing HT.1,4 As a result of these seminal studies, CPX remains a pivotal modality in the initial evaluation of patients with advanced HF, especially those who are considered for HT.1,4

Although the peak Vo2 cutoff of 14 mL/kg per minute remains an important prognostic discriminator in patients with HF, disparities in its prognostic utility may occur when evaluating special populations, including women and obese persons.1,11–13 At the Ochsner Clinic Foundation (OCF), several studies have been conducted exploring other independent prognostic values. These include peak O2 pulse, body fat–adjusted peak O2 pulse, body fat–adjusted peak Vo2, and percentage of predicted Vo2max (an age- and sex-adjusted measure). Herein, we review the experience of the OCF in an attempt to better define a stronger prognosticator of outcome and to more accurately risk stratify patients with systolic HF.

METHODS

We reviewed 3 studies conducted at OCF and published between 1997 and 2004. In addition to being performed at our center, these studies assessed independent predictors of survival in patients with chronic HF and compared these with the standard peak Vo2 described by Mancini et al.10 CPX testing was performed on a treadmill using an individually tailored ramping protocol designed to yield a test duration of 8 to 12 minutes in all studies. Patients were encouraged to exercise until symptoms of chest discomfort or dyspnea were intolerable. Breath-to-breath online gas analysis was performed using a MedGraphics CPXID metabolic card (Medical Graphics Corporation, St. Paul, Minn.).

A prospective observational study by Richards et al11 was conducted between November 1992 and August 1994. It included 76 patients undergoing outpatient HT evaluation referred to a noninvasive laboratory for CPX and followed them for a mean period of 12 months (range, 9–25 months). Entry criteria included New York Hospital Association functional class II or III, left ventricular ejection fraction not exceeding 40%, no symptomatic change on maximum medical therapy for 6 weeks, and ability to exercise on a treadmill. Exclusion criteria included unstable ischemic symptoms, uncontrolled severe hypertension, and inability to undergo treadmill exercise testing. Adverse clinical events were defined as the occurrence of cardiac death or HT.11 The study was designed to compare peak Vo2 with an age- and sex-adjusted measurement (percentage predicted Vo2) as an outcome determinant in women with HF. Percentage of predicted Vo2max was calculated using the formula by Wasserman et al.14

Osman et al15 prospectively studied 225 consecutive ambulatory patients with chronic systolic HF referred for CPX between November 1995 and December 1998. Using the rationale that body fat can represent a significant portion of total body weight and that it consumes essentially no O2, the study assessed the predictive strength of peak Vo2 adjusted to lean body mass (LBM) in determining clinical outcomes in patients with moderate to severe chronic systolic HF. It also attempted to stratify patients into high-risk and low-risk groups based on this value and to define subpopulations that may merit mandatory application of this prognostic criteria. The investigators included patients having HF for at least 6 months receiving stable dosages of medications and having no exacerbations or need for inotropic support for 4 weeks before assessment. Patients with severe peripheral vascular disease, low-threshold angina, and orthopedic limitations preventing them from exercise testing were excluded. Body fat assessment was determined by the skinfold technique using a mean of 3 skinfolds (thigh, chest, and abdomen in men and thigh, triceps, and suprailium in women). Principal outcomes assessed were death due to cardiovascular causes and need for urgent HT. Patients were followed for a median duration of 19.5 months (range, 2–40.4 months; mean [SD], 18.9 [11.3] months).

Peak exercise O2 pulse is another variable derived from CPX, and limited data were available on its prognostic ability in patients with chronic systolic HF.16,17 Lavie et al18 retrospectively studied 209 consecutive ambulatory patients with chronic systolic HF (New York Hospital Association classes I–III) who underwent CPX between January 1996 and December 1998. All patients were diagnosed at a minimum of 6 months before testing and had been receiving stable dosages of medication with no exacerbations or need for inotropic support for 6 weeks. Percentage body fat was also calculated using the 3-skinfold technique. Clinical events were defined as cardiovascular death and urgent HT. The study compared multiple parameters, including anaerobic threshold (AT), ratio of ventilation to carbon dioxide production (VE/VCO2), peak Vo2, peak Vo2 lean (corrected for LBM), O2 pulse, and O2 pulse lean. It also attempted to define the effect of β-blocker use on these prognostic values.

RESULTS

The study by Richards et al11 found that, despite having a lower peak Vo2 than men (18.3 vs 14.5 mg/kg per minute, P  =  .01), women had a higher percentage predicted Vo2max (65.5% vs 75.4%, P  =  .03). In addition, with only one clinical event, women had a higher event-free survival rate (75% vs 95%, P  =  .01).11 The male cohort comprised 6 of 7 urgent HTs and 8 of 8 cardiovascular deaths. These discrepancies in mean peak Vo2, percentage predicted Vo2max, and clinical outcomes suggest that an age- and sex-adjusted value may be a more suitable prognostic tool and perhaps mandatory in certain populations.

Osman et al15 demonstrated superior diagnostic characteristics using the peak Vo2 lean cutoff of 19 mL/kg per minute (Figure 1). During the follow-up period, 29 cardiac events (14 cardiovascular deaths and 15 urgent HTs) were observed. Diagnostic test analysis was used to calculate sensitivity, specificity, likelihood ratios, and positive and negative predictive values for peak Vo2 and for peak Vo2 lean, with the latter being superior to unadjusted peak Vo2 in all diagnostic parameters. Peak Vo2 lean demonstrated better sensitivity and specificity compared with peak Vo2, with values of 72.3% vs 63.6% and 59.3% vs 56%, respectively. Likelihood ratios were also superior using peak Vo2 lean, with 1.78 (95% confidence interval [CI], 1.30–2.45) vs 1.45 (95% CI, 1.01–2.08) for a positive test result and 0.46 (95% CI, 0.23–0.92) vs 0.65 (95% CI, 0.37–1.15) for a negative test result. In addition, positive predictive value and negative predictive value were higher using the LBM-adjusted value, with 20.1% vs 16.9% and 93.9% vs 91.7%, respectively. Other parameters were observed; although cutoffs of percentage predicted Vo2 not exceeding 50% and of peak Vo2 not exceeding 14 mL/kg per minute showed a trend toward significance in the studied population, a peak Vo2 lean not exceeding 19 mg/kg per minute correlated best with the combined end point (P  =  .0006). At 12 months, patients with peak Vo2 lean not exceeding 19 mg/kg per minute had a survival of 80% compared with 98% for those with values exceeding 19 mL/kg per minute (P  =  .001).15

Figure 1
Figure 1 Kaplan-Meier survival curves using both peak oxygen consumption (Vo2) of 14 mL/kg per minute and peak Vo2 lean of 19 mL/kg per minute as cutoffs show stronger prognostic value for the fat-adjusted peak Vo2 by log-rank testing. Reproduced with permission from Osman et al.15

In addition, discordant variable analysis of data by Osman et al15 revealed that none of 8 patients having peak Vo2 not exceeding 14 mL/kg per minute and having peak Vo2 lean of at least 19 mL/kg per minute reached any of the outcomes. Most of these patients were obese (6 of 8) and female (5 of 8). Conversely, 4 of 10 patients having peak Vo2 of at least 14 mL/kg per minute and having peak Vo2 lean not exceeding 19 mL/kg per minute had major events (2 required urgent HT and 2 died of progressive HF). These data further elucidate the incremental prognostic value of body fat–adjusted peak Vo2 vs the standard unadjusted value. Furthermore, by subgroup analysis, women had lower total body weight (P  =  .02), had higher percentage body fat (P < .0001), and achieved lower mean (SD) unadjusted peak Vo2 (13.5 [5.2] vs 16.2 [5.8] mL/kg per minute, P  =  .0002), but no statistical difference was observed when peak Vo2 lean was used (18.8 [7.6] vs 20.4 [7.5] mL/kg per minute, P  =  .11), and no difference in outcome was observed (13.2% of women reached an outcome compared with 18.8% of men, P  =  .4). Obese patients showed lower mean (SD) AT (11.5 [3.5] vs 12.7 [4.2] mL/kg per minute, P  =  .03) and unadjusted peak Vo2 (14.4 [4.7] vs 16.5 [6.1] mL/kg per minute, P  =  .04) but similar peak Vo2 lean (19.3 [6.7] vs 20.5 [7.9] mL/kg per minute, P  =  .2), and there was no statistical difference in outcome (10% of obese patients reached an end point vs 17.8% of nonobese individuals, P  =  .1).15

The study by Lavie et al18 revealed that patients with clinical events (28 of 209) had a statistically significant lower percentage predicted peak Vo2, peak Vo2, peak Vo2 lean, O2 pulse, and O2 pulse lean and a higher VE/VCO2 ratio. As previously noted by Osman et al,15 LBM-adjusted values provided more accurate discrimination between patients with events and patients without events. Peak Vo2 was lower in patients with events (P  =  .01), as was peak Vo2 lean (P < .0001). A cutoff for peak Vo2 lean of 19 mL/kg per minute was a better predictor of prognosis than the classic peak Vo2 cutoff of 14 mL/kg per minute (P  =  .0003). The same held true for AT (P < .01) and for AT lean (P < .001). The best AT cutoff to differentiate patients with and without events was 13 mL/kg per minute (P  =  .04). Its prognostic value further improved after adjusting the AT to LBM with a cutoff value of 16 mL/kg per minute. Last, peak O2 pulse and peak O2 pulse lean were significantly lower in patients with clinical outcomes compared with event-free patients (P < .0001 for both); however, O2 pulse lean cutoff of 14 mL/beat improved prediction of event-free survival compared with the unadjusted value cutoff of 10 mL/beat (P  =  .0002 and P  =  .01, respectively). Figure 2 and Figure 3 show event-free survival when applying cutoffs for AT and O2 pulse vs their respective LBM-adjusted values.

Figure 2
Figure 2 Kaplan-Meier survival curves using both anaerobic threshold (AT) of 13 mL/kg per minute and AT lean of 16 mL/kg per minute as cutoffs for predicting event-free survival. Reproduced with permission from Lavie et al.18
Figure 3
Figure 3 Kaplan-Meier survival curves using both oxygen (O2) pulse of 10 mL/beat and O2 pulse lean of 14 mL/beat as cutoffs for predicting event-free survival. Reproduced with permission from Lavie et al.18

Lavie et al18 also compared peak Vo2 and O2 pulse. Both parameters predicted prognosis, particularly when corrected for LBM. Although a cutoff of 19 mL/kg per minute for peak Vo2 lean was superior to unadjusted peak Vo2 (cutoff, 14 mL/kg per minute), peak O2 pulse lean was similar to or superior to peak Vo2 lean in predicting major clinical events, particularly in subgroups with increased body fat (eg, obese individuals and women). This was suggested by the study data; however, clinical events were too few (4 and 8 for obese and female patients, respectively) for meaningful analysis. The VE/VCO2 ratio was significant in univariate analysis, but it did not add significantly to the Vo2 data in the multivariate models. Direct comparison of LBM-adjusted values and VE/VCO2 slope was not performed.

The effect of β-blocker use was also explored. There was no difference in clinical events among patients receiving and not receiving β-blockers. However, patients receiving β-blockers had higher O2 pulse and O2 pulse lean. All parameters seemed to provide considerably better prognostic stratification in patients not taking β-blockers, although the number of patients receiving β-blockers and the number of events in this group may have been too few for a meaningful analysis.

DISCUSSION

CPX testing is considered the “gold standard” for assessment of functional capacity and for establishment of prognosis in patients with HF.1,7,19,20 Studies by Weber and Janicki7 and later by Szlachcic et al8 initially proposed the prognostic utility of CPX in patients with HF.11 Subsequent studies by Cohn et al9 and by Mancini et al10 led to the standard peak Vo2 cutoff of 14 mg/kg per minute for good prognosis and safe deferral of HT in the near term.15 Richards et al11 attempted to identify if sex-specific differences exist in the ability of peak Vo2 to risk stratify ambulatory patients with HF. They analyzed an age- and sex-adjusted variable (percentage predicted Vo2) and assessed its potential as a better discriminatory value. Their findings revealed decreased peak Vo2 in women compared with men, increased percentage predicted peak Vo2, and improved survival. Women have a higher percentage of non-O2-consuming body fat than men, and this may lead to a pseudoreduction of peak Vo2 in women.11 Furthermore, percentage predicted peak Vo2 has been suggested as an additional prognostic variable, particularly for patients who have peak Vo2 less than 14 mg/kg per minute.21,22 This discrepancy across the sex line, as well as the known contribution of body fat changes in Vo2, led to examination of the effect of LBM-adjusted values such as peak Vo2, AT, and O2 pulse.15

CPX testing parameters used to predict prognosis in patients with HF (including the already mentioned peak Vo2) are corrected for total body weight as opposed to LBM. For practical purposes, fat consumes virtually no O2 and receives minimal perfusion.11,15,23,24 In addition, body fat composition varies greatly across populations.15,24,25 It has been previously proposed that CPX may lose prognostic power in certain subgroups with high percentages of body fat such as women and obese patients.1,7,19,20 All studies reviewed herein demonstrated that simple adjustment of metabolic parameters to LBM provides much greater prognostic strength than the traditionally reported unadjusted peak Vo2, with peak Vo2 lean (cutoff, 19 mL/kg per minute) and peak O2 pulse lean (cutoff, 14 mL/kg per minute) being the strongest predictors. The study by Osman et al15 confirmed the hypothesis that peak Vo2 lean is superior to unadjusted peak Vo2 when risk stratifying patients with systolic HF (Figure 1). Lavie et al18 subsequently obtained similar results in regard to peak Vo2 lean, further supporting better prognostication with the LBM-adjusted value. Additional analysis of data by Lavie et al18 revealed stronger prognostic power for other LBM-adjusted parameters as well, including AT and peak O2 pulse (Figures 2 and 3). As obesity reaches epidemic proportions in westernized society, with almost 70% of adults classified as overweight or obese,19,25,26 correction of these values to LBM may prove to be mandatory when evaluating patients with chronic systolic HF who are being considered for HT.

Other centers have studied additional parameters for prognostication in patients with HF. Values that incorporate VE have proven to be clinically valuable.27 The prognostic value of the VE/VCO2 slope has been proposed as being superior or equal to the standard peak Vo2.27–37 Arena et al27 suggested that the VE/VCO2 slope may be the single most clinically valuable CPX variable (cutoff, 34 [values ≥34 represent poor prognosis]). The oxygen uptake efficiency slope (OUES), which represents the logarithmic relationship between VE and Vo2, is another variable that has reported prognostic superiority compared with the standard peak Vo2.38 Initially, Baba et al39 reported a significant correlation between OUES and peak Vo2 in patients with HF. This correlation was later confirmed by Van Laethem et al,40 and Davies et al38 more recently found that OUES (cutoff, 1.47 [values <1.47 represent poor prognosis]) was a significant predictor of mortality in patients with HF and was superior to other parameters, including VE/VCO2 slope and peak Vo2. Additional investigations by Arena et al27 produced discrepant findings, with both VE/VCO2 slope and OUES being superior to peak Vo2 but with the former being superior to the latter. This discrepancy may be explained by the length of follow-up in the studies (3 years27 vs 9 years38) and/or by the assessment of OUES as log OUES in the study by Davies et al.27,38 Despite increasing evidence that supports the prognostic utility of these parameters, no single study (to our knowledge) has compared the prognostic value of VE/VCO2 slope or OUES with peak Vo2 lean or O2 pulse lean, and further investigation is warranted.

A known limitation of peak Vo2 and O2 pulse is underestimation of these values due to early cessation of the exercise test before maximal physiologic effort41 (typically defined as a respiratory exchange ratio <1.0). The VE/VCO2 slope has been demonstrated to retain prognostic power even when calculated with suboptimal effort test data.27,36,41 This finding may be explained by the relatively linear relationship between VE and VCO2. Although VE/VCO2 slope retains prognostic value despite suboptimal patient effort, it is a stronger predictor of mortality when calculated from data obtained during the entire duration of the test.27,42 This is due to its bilinear relationship in a significant number of patients, one representing the initial minutes of exercise and one after the ventilatory compensation phase or AT.42 The OUES has also been proposed as having prognostic utility when calculated during submaximal exercise. Van Laethem et al40 found that OUES varies by less than 3% when calculated at different stages of exercise. Similarly, Davies et al38 found variability of only 1% in OUES when calculated with data from half of the exercise duration and with full exercise data. Arena et al27 compared the prognostic ability of VE/VCO2 slope and OUES when calculated using data collected during the first half of the exercise test; VE/VCO2 slope was found to be superior in their study, although the difference was not statistically significant. Increasing evidence suggests that assessment of these parameters may in fact provide the best prognosis stratification in patients who are unable to reach maximal physiologic effort during CPX.

To our knowledge, no specific variable has been proven to be significantly superior in predicting hospitalization. However, Arena et al found strong correlation between cardiac-related hospitalization and several of the studied parameters, specifically VE/VCO2 slope, exercise partial pressure of end-tidal carbon dioxide43 (PETCO2), and resting PETCO2.44 A later study45 by the same group of investigators found that resting PETCO2 (cutoff, 33 mm Hg [values ≤33 mm Hg indicate poor prognosis]) also has prognostic value when applied to major cardiac events or death, especially in combination with other variables (New York Heart Association class, left ventricular ejection fraction, and VE/VCO2 slope). Furthermore, in that study, resting PETCO2 added prognostic power to VE/VCO2 slope.

The increasing number of parameters shown to provide significant prognostic value demonstrates a need for a simplified method to integrate these data. An attempt to develop a simplified multivariate score for CPX-derived metabolic parameters was recently published by Myers et al.46 Assignment of a weighted score to CPX response (peak Vo2), ventilatory efficiency (VE/VCO2 slope, PETCO2, and OUES), and hemodynamic responses (heart rate recovery47) produced a graded score (CPX score). The score had stronger prognostic power for major and minor cardiac events (cardiac-related hospitalization, HT, left ventricular assist device implantation, or cardiac-related death) than any single parameter. However, the data were not sufficient to validate the score.

The prognostic ability of CPX parameters in patients taking β-blockers is also under question. Although findings at the OCF suggest that parameters derived from CPX provide better prognostic stratification in patients not taking β-blockers,18 other results have shown that peak Vo2 and VE/VCO2 slope provide better stratification for patients being treated with these medications.48 In investigations performed at the OCF, peak Vo2 provided particularly poor prognostic stratification, and peak O2 pulse lean provided the best prognostic stratification in patients taking β-blockers. However, in the study by Lavie et al18 that evaluated the effect of β-blocker use on CPX data, the number of patients taking β-blockers and the number of events in this subgroup were too few to provide meaningful analysis. The use of peak O2 pulse (a value that is more dependent on cardiac pump reserve) seems promising for prognostic stratification in patients treated with β-blockers. Larger patient populations with optimal medical therapy during this era of β-blocker use may be necessary to provide more accurate stratification.

CONCLUSION

Studies at OCF have consistently demonstrated the superior prognostic value of LBM-adjusted parameters over the standard peak Vo2. Correction of these parameters should be strongly considered when evaluating patients with HF, especially those being considered for HT. Other parameters, including but not limited to VE/VCO2 slope, OUES, and resting and exercise PETCO2, have proven superiority over the standard peak Vo2 and are especially valuable when evaluating data obtained from submaximal exercise. To our knowledge, no study has compared the prognostic power of these parameters versus that of peak Vo2 lean or O2 pulse lean. Future studies are needed to assess the prognostic value of various CPX parameters (including VE/VCO2 slope) using body fat–adjusted peak Vo2 in patients with HF.49 Sex, age, obesity, and (more recently) race/ethnicity49,50 have been shown to affect exercise capacitance and CPX-derived parameters. A composite of several CPX parameters, including VE/VCO2 slope, peak Vo2 (especially if adjusted for percent body fat), OUES, resting PETCO2, and heart rate recovery, as has been recently suggested,46 may best predict HF prognosis.49

REFERENCES

  1. ↵
    1. Milani R. V.,
    2. Lavie C. J.,
    3. Mehra M. R.,
    4. Ventura H. O.
    (2006) Understanding the basics of cardiopulmonary exercise testing. Mayo Clin Proc 81(12):1603–1611, pmid:17165639.
    OpenUrlCrossRefPubMed
    1. Lavie C. J.,
    2. Lubin M. F.
    1. Vivekananthan K.,
    2. Lavie C. J.,
    3. Milani R. V.
    (2000) in Clinics Atlas of Office Procedures: Cardiovascular Disease, Stress testing, eds Lavie C. J., Lubin M. F. (WB Saunders Co, Philadelphia, PA), pp 377–391.
  3. ↵
    1. Milani R. V.,
    2. Lavie C. J.,
    3. Spiva H.
    (1995) Limitations of estimating metabolic equivalents in exercise assessment in patients with coronary artery disease. Am J Cardiol 75(14):940–942, pmid:7733007.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Milani R. V.,
    2. Lavie C. J.,
    3. Mehra M. R.
    (2004) Cardiopulmonary exercise testing: how do we differentiate the cause of dyspnea? Circulation 110(4):e27–e31, pmid:15277333.
    OpenUrlFREE Full Text
  5. ↵
    1. Weber K. T.,
    2. Janicki J. S.,
    3. Shroff S. G.,
    4. Likoff M. J.
    (1983) The cardiopulmonary unit: the body's gas transport system. Clin Chest Med 4(2):101–110, pmid:6342917.
    OpenUrlPubMed
  6. ↵
    1. Wasserman K.,
    2. Hansen J. E.,
    3. Sue D. Y.,
    4. Casaburi R.,
    5. Whipp B. J.
    (1999) Principles of Exercise Testing and Interpretation. 3rd ed (Lippincott Williams & Wilkins, Philadelphia, PA).
  7. ↵
    1. Weber K. T.,
    2. Janicki J. S.
    (1985) Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am J Cardiol 55(2):22A–31A.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Szlachcic J.,
    2. Massie B. M.,
    3. Kramer B. L.,
    4. Topic N.,
    5. Tubau J.
    (1985) Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 55(8):1037–1042, pmid:3984864.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Cohn J. N.,
    2. Johnson G.,
    3. Ziesche S.,
    4. et al.
    (1991) A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 325(5):303–310, pmid:2057035.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Mancini D. M.,
    2. Eisen H.,
    3. Kussmaul W.,
    4. Mull R.,
    5. Edmunds L. H. Jr.,
    6. Wilson J. R.
    (1991) Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 83(3):778–786, pmid:1999029.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Richards D. R.,
    2. Mehra M. R.,
    3. Ventura H. O.,
    4. et al.
    (1997) Usefulness of peak oxygen consumption in predicting outcome of heart failure in women versus men. Am J Cardiol 80(9):1236–1238, pmid:9359563.
    OpenUrlCrossRefPubMed
    1. Lavie C. J.,
    2. Milani R.,
    3. Mehra M. R.,
    4. Ventura H. O.,
    5. Messerli F. H.
    (2002) Obesity weight reduction and survival in heart failure [letter]. J Am Coll Cardiol 39(9):1563, author reply 1563–1564, pmid:11985924.
    OpenUrlPubMed
  13. ↵
    1. Lavie C. J.,
    2. Osman A. F.,
    3. Milani R. V.,
    4. Mehra M. R.
    (2003) Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol 91(7):891–894, pmid:12667583.
    OpenUrlCrossRefPubMed
  14. ↵
    1. Wasserman K.,
    2. Hansen J. E.,
    3. Sue D. Y.,
    4. Whipp B. J.
    (1986) Principles of Exercise Testing and Interpretation (Lea & Febiger, Philadelphia, PA), p 73.
  15. ↵
    1. Osman A. F.,
    2. Mehra M. R.,
    3. Lavie C. J.,
    4. Nunez E.,
    5. Milani R. V.
    (2000) The incremental prognostic importance of body fat adjusted peak oxygen consumption in chronic heart failure. J Am Coll Cardiol 36(7):2126–2131, pmid:11127451.
    OpenUrlFREE Full Text
  16. ↵
    1. Cohen-Solal A.,
    2. Tabet J. Y.,
    3. Logeart D.,
    4. Bourgoin P.,
    5. Tokmakova M.,
    6. Dahan M.
    (2002) A non-invasively determined surrogate of cardiac power (“circulatory power”) at peak exercise is a powerful prognostic factor in chronic heart failure. Eur Heart J 23(10):806–814, pmid:12009721.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Cohen-Solal A.,
    2. Barnier P.,
    3. Pessione F.,
    4. et al.
    (1997) Comparison of the long-term prognostic value of peak exercise oxygen pulse and peak oxygen uptake in patients with chronic heart failure. Heart 78(6):572–576, pmid:9470873.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Lavie C. J.,
    2. Milani R. V.,
    3. Mehra M. R.
    (2004) Peak exercise oxygen pulse and prognosis in chronic heart failure. Am J Cardiol 93(5):588–593, pmid:14996584.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Artham S. M.,
    2. Lavie C. J.,
    3. Milani R. V.,
    4. Ventura H. O.
    (2007) The obesity paradox and discrepancy between peak oxygen consumption and heart failure prognosis: it's all in the fat. Congest Heart Fail 13(3):177–180, pmid:17541313.
    OpenUrlPubMed
  20. ↵
    1. Mehra M. R.,
    2. Lavie C. J.,
    3. Milani R. V.
    (1996) Predicting prognosis in advanced heart failure: use of exercise indices. Chest 110(2):310–312, pmid:8697822.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Osada N.,
    2. Chaitman B. R.,
    3. Miller L. W.,
    4. et al.
    (1998) Cardiopulmonary exercise testing identifies low risk patients with heart failure and severely impaired exercise capacity considered for heart transplantation. J Am Coll Cardiol 31(3):577–582, pmid:9502638.
    OpenUrlFREE Full Text
  22. ↵
    1. Aaronson K. D.,
    2. Mancini D. M.
    (1995) Is percentage of predicted maximal exercise oxygen consumption a better predictor of survival than peak exercise oxygen consumption for patients with severe heart failure [published correction appears in J Heart Lung Transplant. 1996;15(1, pt 1):106–107]? J Heart Lung Transplant 14(5):981–989, pmid:8800737.
    OpenUrlPubMed
  23. ↵
    1. Milani R. V.,
    2. Mehra M. R.,
    3. Reddy T. K.,
    4. Lavie C. J.,
    5. Ventura H. O.
    (1996) Ventilation/carbon dioxide production ratio in early exercise predicts poor functional capacity in congestive heart failure. Heart 76(5):393–396, pmid:8944583.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Milani R. V.,
    2. Lavie C. J.
    (1998) The effects of body composition changes to observed improvements in cardiopulmonary parameters after exercise training with cardiac rehabilitation. Chest 113(3):599–601, pmid:9515831.
    OpenUrlCrossRefPubMed
  25. ↵
    1. Lavie C. J.,
    2. Milani R. V.
    (2003) Obesity and cardiovascular disease: the Hippocrates paradox? J Am Coll Cardiol 42(4):677–679, pmid:12932600.
    OpenUrlFREE Full Text
  26. ↵
    1. Manson J. E.,
    2. Bassuk S. S.
    (2003) Obesity in the United States: a fresh look at its high toll. JAMA 289(2):229–230, pmid:12517236.
    OpenUrlCrossRefPubMed
  27. ↵
    1. Arena R.,
    2. Myers J.,
    3. Hsu L.,
    4. et al.
    (2007) The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope. J Card Fail 13(6):462–469, pmid:17675060.
    OpenUrlCrossRefPubMed
    1. Chua T. P.,
    2. Ponikowski P.,
    3. Harrington D.,
    4. et al.
    (1997) Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol 29(7):1585–1590, pmid:9180123.
    OpenUrlFREE Full Text
    1. Kleber F. X.,
    2. Vietzke G.,
    3. Wernecke K. D.,
    4. et al.
    (2000) Impairment of ventilatory efficiency in heart failure: prognostic impact. Circulation 101(24):2803–2809, pmid:10859285.
    OpenUrlAbstract/FREE Full Text
    1. Bol E.,
    2. de Vries W. R.,
    3. Mosterd W. L.,
    4. Wielenga R. P.,
    5. Coats A. J.
    (2000) Cardiopulmonary exercise parameters in relation to all-cause mortality in patients with chronic heart failure. Int J Cardiol 72(3):255–263, pmid:10716136.
    OpenUrlCrossRefPubMed
    1. Corrá U.,
    2. Mezzani A.,
    3. Bosimini E.,
    4. Scapellato F.,
    5. Imparato A.,
    6. Giannuzzi P.
    (2002) Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity. Am Heart J 143(3):418–426, pmid:11868046.
    OpenUrlCrossRefPubMed
    1. Corrá U.,
    2. Giordano A.,
    3. Bosimini E.,
    4. et al.
    (2002) Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications. Chest 121(5):1572–1580, pmid:12006446.
    OpenUrlCrossRefPubMed
    1. Koike A.,
    2. Itoh H.,
    3. Kato M.,
    4. et al.
    (2002) Prognostic power of ventilatory responses during submaximal exercise in patients with chronic heart disease. Chest 121(5):1581–1588, pmid:12006447.
    OpenUrlCrossRefPubMed
    1. Gitt A. K.,
    2. Wasserman K.,
    3. Kilkowsky C.,
    4. et al.
    (2002) Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation 106(24):3079–3084, pmid:12473555.
    OpenUrlAbstract/FREE Full Text
    1. Francis D. P.,
    2. Shamim W.,
    3. Davies L. C.,
    4. et al.
    (2000) Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO2 slope and peak Vo2. Eur Heart J 21(2):154–161, pmid:10637089.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Arena R.,
    2. Myers J.,
    3. Aslam S. S.,
    4. Varughese E. B.,
    5. Peberdy M. A.
    (2004) Peak Vo2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison. Am Heart J 147(2):354–360, pmid:14760336.
    OpenUrlCrossRefPubMed
  37. ↵
    1. Arena R.,
    2. Humphrey R.
    (2002) Comparison of ventilatory expired gas parameters used to predict hospitalization in patients with heart failure. Am Heart J 143(3):427–432, pmid:11868047.
    OpenUrlCrossRefPubMed
  38. ↵
    1. Davies L. C.,
    2. Wensel R.,
    3. Georgiadou P.,
    4. et al.
    (2006) Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope. Eur Heart J 27(6):684–690, pmid:16338939.
    OpenUrlCrossRefPubMed
  39. ↵
    1. Baba R.,
    2. Nagashima M.,
    3. Goto M.,
    4. et al.
    (1996) Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise. J Am Coll Cardiol 28(6):1567–1572, pmid:8917273.
    OpenUrlFREE Full Text
  40. ↵
    1. Van Laethem C.,
    2. Bartunek J.,
    3. Goethals M.,
    4. Nellens P.,
    5. Andries E.,
    6. Vanderheyden M.
    (2005) Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients. Am Heart J 149(1):175–180, pmid:15660050.
    OpenUrlCrossRefPubMed
  41. ↵
    1. Arena R.,
    2. Humphrey R.,
    3. Peberdy M. A.
    (2003) Prognostic ability of VE/VCO2 slope calculations using different exercise test time intervals in subjects with heart failure. Eur J Cardiovasc Prev Rehabil 10(6):463–468, pmid:14671470.
    OpenUrlCrossRefPubMed
  42. ↵
    1. Tabet J. Y.,
    2. Beauvais F.,
    3. Thabut G.,
    4. Tartière J. M.,
    5. Logeart D.,
    6. Cohen-Solal A.
    (2003) A critical appraisal of the prognostic value of the VE/VCO2 slope in chronic heart failure. Eur J Cardiovasc Prev Rehabil 10(4):267–272, pmid:14555881.
    OpenUrlCrossRefPubMed
  43. ↵
    1. Arena R.,
    2. Guazzi M.,
    3. Myers J.
    (2007) Prognostic value of end-tidal carbon dioxide during exercise testing in heart failure. Int J Cardiol 117(1):103–108, pmid:16843545.
    OpenUrlCrossRefPubMed
  44. ↵
    1. Arena R.,
    2. Peberdy M. A.,
    3. Myers J.,
    4. Guazzi M.,
    5. Tevald M.
    (2006) Prognostic value of resting end-tidal carbon dioxide in patients with heart failure. Int J Cardiol 109(3):351–358, pmid:16046017.
    OpenUrlCrossRefPubMed
  45. ↵
    1. Arena R.,
    2. Myers J.,
    3. Abella J.,
    4. et al.
    (2008) The partial pressure of resting end-tidal carbon dioxide predicts major cardiac events in patients with systolic heart failure. Am Heart J 156(5):982–988, pmid:19061716.
    OpenUrlCrossRefPubMed
  46. ↵
    1. Myers J.,
    2. Arena R.,
    3. Dewey F.,
    4. et al.
    (2008) A cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure. Am Heart J 156(6):1177–1183, pmid:19033016.
    OpenUrlCrossRefPubMed
  47. ↵
    1. Arena R.,
    2. Guazzi M.,
    3. Myers J.,
    4. Peberdy M. A.
    (2006) Prognostic value of heart rate recovery in patients with heart failure. Am Heart J 151(4):851.e7–e13, pmid:16569547.
    OpenUrlCrossRefPubMed
  48. ↵
    1. Guimarães G. V.,
    2. Silva M. S.,
    3. d'Avila V. M.,
    4. Ferreira S. M.,
    5. Silva C. P.,
    6. Bocchi E. A.
    (2008) Peak Vo2 and VE/VCO2 slope in betablockers era in patients with heart failure: a Brazilian experience. Arq Bras Cardiol 91(1):39–48, pmid:18660944.
    OpenUrlPubMed
  49. ↵
    1. Lavie C. J.,
    2. Milani R. V.,
    3. Allerton T. D.
    (2009) Peak oxygen consumption and heart failure prognosis: does race, sex, or fat explain the discrepancy? Congest Heart Fail 15(1):41–42, pmid:19187407.
    OpenUrlPubMed
  50. ↵
    1. Arena R.,
    2. Myers J.,
    3. Abella J.,
    4. et al.
    (2008) Prognostic characteristics of cardiopulmonary exercise testing in caucasian and African American patients with heart failure. Congest Heart Fail 14(6):310–315, pmid:19076854.
    OpenUrlPubMed
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