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Objectives: To determine the utility of an artificial neural network (ANN) in predicting cardiovascular (CV) death in patients with heart failure (HF)., Background: ANNs use weighted inputs in multiple layers of mathematical connections in order to predict outcomes from multiple risk markers. This approach has not been applied in the context of cardiopulmonary exercise testing (CPX) to predict risk in patients with HF., Methods: 2635 patients with HF underwent CPX and were followed for a mean of 29 ± 30 months. The sample was divided randomly into ANN training and testing sets to predict CV mortality. Peak VO2, VE/VCO2 slope, heart rate recovery, oxygen uptake efficiency slope, and end-tidal CO2 pressure were included in the model. The predictive accuracy of the ANN was compared to logistic regression (LR) and a Cox proportional hazards (PH) score. A multi-layer feed-forward ANN was used and was tested with a single hidden layer containing a varying number of hidden neurons., Results: There were 291 CV deaths during the follow-up. An abnormal VE/VCO2 slope was the strongest predictor of CV mortality using conventional PH analysis (hazard ratio 3.04; 95% CI 2.2-4.2, p<0.001). After training, the ANN was more accurate in predicting CV mortality compared to LR and PH; ROC areas for the ANN, LR, and PH models were 0.72, 0.70, and 0.69, respectively. Age and BMI-adjusted odds ratios were 4.2, 2.6, and 2.9, for ANN, LR, and PH, respectively., Conclusion: An ANN model slightly improves upon conventional methods for estimating CV mortality risk using established CPX responses., (Published by Elsevier Ireland Ltd.)

Background: Heart rate recovery (HRR) has been observed to be a significant prognostic measure in patients with heart failure (HF). However, the prognostic value of HRR has not been examined in regard to the level of patient effort during exercise testing. Using the peak respiratory exchange ratio (RER) and a large multicenter HF database we examined the prognostic utility of HRR., Methods: Cardiopulmonary exercise testing (CPX) was performed in 806 HF patients who then underwent an active cool-down of at least 1 min. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), and peak RER were determined with subjects categorized into subgroups according to peak RER (<1.00, 1.00-1.09, ≥ 1.10). HRR was defined as the difference between heart rate at peak exercise and 1 min following test termination. Patients were followed for major cardiac events for up to four years post-CPX., Results: There were 163 major cardiac events (115 deaths, 20 left ventricular assist device implantations, and 28 transplantations) during the four year tracking period. Univariate Cox regression analysis results identified HRR as a significant (p<0.05) univariate predictor of adverse events regardless of the RER achieved. Multivariate Cox regression analysis in the overall group revealed that the VE/VCO2 slope was the strongest predictor of adverse events (chi-square: 110.9, p<0.001) with both HRR (residual chi-square: 16.7, p<0.001) and peak VO2 (residual chi-square: 10.4, p<0.01) adding significant prognostic value., Conclusions: HRR after symptom-limited exercise testing performed at sub-maximal efforts using RER to categorize level of effort is as predictive as HRR after maximal effort in HF patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Cardiopulmonary exercise test (CPX) responses are strong predictors of outcomes in patients with heart failure. We recently developed a CPX score that integrated the additive prognostic information from CPX. The purpose of this study was to validate the score in a larger, independent sample of patients., Methods and Results: A total of 2625 patients with heart failure underwent CPX and were followed for cardiovascular (CV) mortality and major CV events (death, transplantation, left ventricular assist device implantation). Net reclassification improvement (NRI) for the score and each of its components were determined at 3 years. The VE/VCO2 slope was the strongest predictor of risk and was attributed a relative weight of 7, with weighted scores for abnormal heart rate recovery, oxygen uptake efficiency slope, end-tidal CO2 pressure, and peak VO2 having scores of 5, 3, 3, and 2, respectively. A summed score of >15 was associated with an annual mortality rate of 12.2% and a relative risk >9 for total events, whereas a score of <5 was associated with an annual mortality rate of 1.2%. The composite score was the most accurate predictor of CV events among all CPX responses considered (C indexes, 0.70 for CV mortality and 0.72 for the composite outcome). Each component of the score provided significant NRI compared with peak VO2 (category-free NRI, 0.61-0.77), and the score provided significant NRI above clinical risk factors for both CV events and mortality (NRI, 0.63 and 0.65 for CPX score compared with clinical variables alone)., Conclusions: These results validate the application of a simple, integrated multivariable score based on readily available CPX responses.

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO(2)), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO(2) (7,319), VE/VCO(2) slope (5,044), EOV (1,617), and OUES (584). Peak VO(2), the VE/VCO(2) slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO(2) and the VE/VCO(2) slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.

Background: Minute ventilation/CO(2) production (VE/Vco(2)) slope is an index determined by cardiopulmonary exercise testing, which incorporates pertinent cardiac, pulmonary, and skeletal muscle physiology into a substantive composite assessment. The VE/Vco(2) slope has many applications, including utility as a well-validated prognostic gauge for patients with heart failure (HF). In this study, we combine VE/Vco(2) slope with systolic blood pressure, creating a novel index that we labeled ventilatory power. Ventilatory power links the combined physiology inherent in the VE/Vco(2) slope to peripheral pressure, adding an additional dimension pertinent to HF assessment. Whereas the related concept of circulatory power links peak oxygen consumption with peak systolic blood pressure as a prognostic index, we hypothesized that ventilatory power would provide greater prognostic discrimination than VE/Vco2 slope, peak oxygen consumption, and circulatory power for patients with systolic HF., Methods and Results: Patients with systolic HF (left ventricular ejection fraction ≤35%) underwent symptom-limited cardiopulmonary exercise testing as part of routine management and were followed for up to 4 years for major cardiac events (mortality, left ventricular assist device implantation, and heart transplantation). Eight hundred seventy-five patients with HF (left ventricular ejection fraction, 26±9%; mean age, 55±14) were studied. Cardiopulmonary exercise testing indices peak oxygen consumption, VE/Vco(2) slope, circulatory power, and ventilatory power were all predictive of cardiac events (P<0.001). Multivariate analysis demonstrated that ventilatory power was the strongest indicator of prognosis., Conclusions: Although circulatory power and traditional cardiopulmonary exercise testing parameters can be used to predict prognosis among patients with HF, ventilatory power provides relatively greater prognostic discrimination and may constitute a relatively more useful composite tool.

Introduction: While the medical management strategy for patients with heart failure (HF) has dramatically changed, cardiopulmonary exercise testing (CPX) procedures and the data obtained have remained relatively stable. We are unaware of any previous investigation that has assessed differences in the prognostic utility of CPX in HF according to time period, reflecting differences in the clinical management of systolic HF., Methods: Subjects (n = 381) underwent CPX between April 1, 1993, and December 31, 2005, and the remaining 511 were tested between January 1, 2006, and October 28, 2010. Peak oxygen uptake ((Equation is included in full-text article.)O2) and the minute ventilation/carbon dioxide production ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) slope were ascertained for all tests., Results: Both the (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope and peak (Equation is included in full-text article.)O2 were strong univariate predictors of adverse events in both subgroups. In the multivariate analysis, the (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope was the strongest predictive marker while peak (Equation is included in full-text article.)O2 added predictive value and was retained in the regression for all scenarios. In subjects undergoing CPX before 2006, a (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope 45 or greater and a peak (Equation is included in full-text article.)O2 of less than 10 mL · kg · min generated a hazard ratio of 4.2 (95% CI: 1.9-9.1, P < .001) when considering only mortality as an endpoint. In subjects undergoing CPX after 2006, a (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope 45 or greater and a peak (Equation is included in full-text article.)O2 of less than 10 mL · kg · min generated a hazard ratio of 8.2 (95% CI: 4.7-14.3, P < .001) when considering only mortality as an endpoint., Conclusion: The results of this study indicate that CPX continues to be a valuable clinical assessment in the present-day HF management.

Background: Previous research has demonstrated the prognostic value of cardiopulmonary exercise testing (CPX) in elderly patients with heart failure (HF). Investigations that have comprehensively examined the value of CPX across different age groups are lacking. The purpose of the present investigation was to evaluate the prognostic value of CPX in young, middle-aged and older patients with HF., Methods: A total of 1605 subjects (age: 59.2 ± 13.7 years, 78% male) underwent CPX and were subsequently tracked for major cardiac events. Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO(2)), both absolute and percent-predicted, were determined. The prognostic value of these CPX variables was assessed in ≤ 45, 46-65 and ≥ 66 year subgroups., Results: The three year event rates for major cardiac events in the ≤ 45, 46-65 and ≥ 66 year subgroups were 8.8%, 6.0% and 5.7%, respectively. The VE/VCO(2) slope (Hazard ratio ≥ 1.07, p<0.001), peak VO(2) (Hazard ratio ≤ 0.87, p<0.001) and percent-predicted peak VO(2) (Hazard ratio 0 ≤ 0.98, p<0.001) were all significant prognostic markers in each age subgroup. While the VE/VCO(2) slope carried the greatest prognostic strength, peak VO(2) and percent-predicted peak VO(2) were retained in multivariate analyses (Residual Chi-Square ≥ 5.2, p<0.05). With respect to peak VO(2), the actual value was the more robust prognostic marker in the ≤ 45 and ≥ 66 year subgroups while the percent-predicted expression provided better predictive resolution in subjects who were 46-65 years old., Conclusions: These results indicate that, irrespective of a patient's age at presentation, CPX provides valuable prognostic information in the HF population., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Peak oxygen uptake (VO₂) is prognostic for morbidity and mortality. Estimating aerobic capacity during traditional exercise stress testing is common as it has been shown that total treadmill time on the Bruce protocol predicts peak VO₂. However, the potential to overestimate peak VO2 exists and may have clinical implications regarding the interpretation of exercise test data., Methods: Subjects (N = 303) with symptoms suggestive of myocardial ischemia underwent a myocardial perfusion study and an exercise test with simultaneous ventilatory expired gas analysis. Estimated peak VO₂ from the Bruce treadmill protocol was compared with measured peak VO₂. The Duke Treadmill Score (DTS) was calculated with treadmill time (DTS(time)) and also with measured VO₂ (DTS(measured)),expressed as metabolic equivalents (METs), and converted to time., Results: Peak measured METs was significantly lower than peak estimated METs in the entire cohort (6.5 ± 1.9 vs 8.8 ± 2.8, P < .001) as well as in female (5.7 ± 1.4 and 7.8 ± 2.1, P < .001) and male (7.3 ± 2.0 and 9.7 ± 3.1, P < .001) subgroups. Calculation of the DTS with measured METs resulted in a significantly lower score compared with its calculation with treadmill time (2.7 ± 3.5 vs 5.8 ± 4.6, P < .001). Receiver operating characteristic curve analysis revealed that DTS(measured) produce a statistically significant model for diagnosing a perfusion defect in both men and women (P < .05), whereas DTS(time) was diagnostic only in men (P < .05)., Discussion: This study demonstrates that estimates of aerobic capacity are significantly higher than measured values and this difference may result in a significant underestimation of morbidity/mortality risk.

Objectives: Chest pain is a common reason for accessing an emergency department (ED) and a frequent cause of outpatient physician visits. Whether patients referred for cardiac stress testing from these referral sources differ in clinically significant ways is unknown, and is thus the purpose of this investigation., Methods: This study prospectively assessed 301 patients presenting to Virginia Commonwealth University Medical Center with symptoms suggestive of myocardial ischemia. All subjects underwent nuclear stress testing as a part of their assessment., Results: Patients referred from the ED were more likely to be African American and outpatients were more likely to be Caucasian. Outpatients were older than those referred from the ED. Patients referred from the ED were less likely to have a diagnosis of hypertension, dyslipidemia, or diabetes, but were more likely to smoke. The exercise response was similar, with a few exceptions. There were no differences in the frequency of equivocal or positive nuclear stress test results based on referral source., Conclusions: The results of the present study indicate that several characteristics of patients undergoing outpatient nuclear stress testing differ according to referral source. Future research should be directed toward developing effective strategies to reduce ED utilization and increasing outpatient management.

Objective: To determine if the attainment of at least 85% of age-predicted maximal heart rate (APMHR), using the equation 220 - age, and/or at least 25,000 as the product of maximal heart rate and systolic blood pressure (rate pressure product, RPP) is an accurate indicator of exertion level during exercise stress testing., Patients and Methods: From May 1, 2009, to February 15, 2010, 238 patients (mean ± SD age, 49.3±11.9 years; 50% male) with symptoms suggestive of myocardial ischemia underwent an exercise stress test with the addition of ventilatory expired gas analysis and a myocardial perfusion study. Ventilatory expired gas analysis determined the peak respiratory exchange ratio (RER), which is considered a valid and reliable variable for quantifying a patient's exertion during exercise., Results: Of the patients, 207 (87%) attained a peak RER of 1.00 or more, and 123 (52%) attained a peak RER of 1.10 or more. An APMHR of 85% or more and peak RPP of 25,000 or more were both ineffective in identifying patients who put forth a maximal exercise effort (ie, peak RER, ≥1.10). Perceived exertion was a significant indicator (P=.04) of patient exertion, with a threshold of 15 (6-20 scale) being an optimal cut point. The percentage of equivocal myocardial perfusion study results was significantly higher in patients who demonstrated a submaximal exercise effort by peak RER (P≤.007)., Conclusion: Aerobic exercise testing is an integral component in the assessment of patients with suspected myocardial ischemia. Our findings indicate that the currently used percentage of APMHR and peak RPP thresholds are ineffective in quantifying a patient's level of exertion during exercise stress testing.

Background: Cardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers--peak oxygen consumption (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, and exercise periodic breathing (EPB)-to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients., Methods and Results: A total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO₂ slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO₂ slope and lower peak VO₂. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO₂ slope, whereas peak VO₂ added minimal prognostic power., Conclusions: EPB with an elevated VE/VCO₂ slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO₂ ≤10 mL O₂·kg⁻¹·min⁻¹. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Previous investigations have established the prognostic value of variables obtained from both echocardiography with tissue Doppler Imaging (TDI) and cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). Past prognostic comparisons of variables obtained from these evaluation techniques have been limited to the comparison of left ventricular ejection fraction (LVEF) vs. peak oxygen consumption (VO2). The present investigation undertakes a more thorough correlative and prognostic assessment., Methods: Two hundred and forty-three patients with HF (190 male/53 female, age: 62.2±9.7) underwent echocardiography with TDI and CPX to determine the following variables: 1) the ratio between mitral early (E) to mitral annular (E´) velocity, 2) LVEF, 3) LV mass, 4) LV end systolic volume (LVESV), 5) Peak VO2, 6) The minute ventilation/carbon dioxide production (VE/VCO2) slope, and 7) Exercise oscillatory ventilation (EOV)., Results: There were 43 cardiac-related deaths during the four-year tracking period. In the multivariate analysis, E/E' was the strongest prognostic variable (Chi-square: 46.1, p<0.001). LV mass (Residual chi-square: 16.8, p<0.001), LVESV (Residual chi-square: 8.0, p=0.005) and the VE/VCO2 slope (Residual chi-square: 4.6, p=0.03) all added significant predictive value and were retained in the regression., Conclusions: The results of the present study indicate several variables obtained from echocardiography with TDI are prognostically important in HF. The VE/VCO2 slope, which is one of the strongest prognostic markers obtained from CPX, adds prognostic value to these variables. A combined analysis of both noninvasive techniques may improve the prognostic characterization of patients with HF., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Previous investigations have reported a relationship between variables obtained from echocardiography with tissue Doppler imaging (TDI) and cardiopulmonary exercise testing (CPX) in systolic heart failure (HF) cohorts. The purpose of the present investigation was to perform a comparative analysis between echocardiography with TDI and CPX in patients with HF and normal ejection fraction (NEF)., Methods: Patients with HF-NEF (N = 32) underwent echocardiography with TDI and CPX to determine the following variables: (1) the ratio between mitral early velocity (E) and mitral annular velocity (E'), (2) ejection fraction, (3) left ventricular (LV) mass, (4) left ventricular end systolic volume, (5) peak oxygen uptake (.VO2), (6) ventilatory efficiency, (7) the partial pressure of end-tidal carbon dioxide (P(ET)CO2) at rest and peak exercise, and (8) heart rate recovery at 1 minute (HRR1)., Results: Pearson correlation revealed that E/E' was significantly correlated with peak oxygen uptake (r = -0.55, P = .001), the ventilatory efficiency slope (r = 0.60, P < .001), resting P(ET)CO2 (r = -0.39, P = .03), peak P(ET)CO2 (r = -0.50, P = .004), and HRR1 (r = -0.63, P < .001). Left ventricular mass and left ventricular end systolic volume were not correlated with any CPX variable. Ejection fraction was correlated with HRR1 (r = -0.55, P = .001). An HRR1 threshold of less than 16 and/or 16 or more beats per minute (higher value positive) effectively identified subjects with an E/E' > 10 (positive likelihood ratio: 13:2)., Discussion: E/E' provides an accurate reflection of LV filling pressure and thus, insight into diastolic function. The results of the present investigation indicate CPX provides insight into cardiac dysfunction in patients with HF-NEF and thus, may eventually prove to be a valuable and accepted clinical assessment.

Background: Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO) provide robust prognostic information in patients with heart failure undergoing cardiopulmonary exercise testing (CPX). The purpose of this study is to assess the change in prognostic characteristics of CPX at different time intervals., Methods and Results: Seven hundred ninety-one subjects (74% male, mean age: 60.7+/-12.9 years, ejection fraction: 34.6+/-15.0%, ischemic etiology: 51%) underwent CPX and were tracked for major cardiac events over a 4-year period. All event-free subjects were tracked for at least 3 years. Mean VE/VCO(2) slope and peak VO(2) were 35.0+/-10.0 and 16.0+/-6.4 mL O(2) . kg(-1) . min(-1), respectively. There were a total of 263 major cardiac events (199 deaths, 45 transplants, and 19 left ventricular assist device implantations). Both continuous and dichotomous expressions of the VE/VCO(2) slope and peak VO(2) were prognostically significant up to 18 months post-CPX. Continuous and dichotomous expressions of the VE/VCO(2) slope remained prognostically significant up to 36 months post-CPX, whereas peak VO(2) was not predictive during the third and fourth year of follow-up. In a multivariate analysis, the VE/VCO(2) slope was consistently the superior prognostic marker, whereas peak VO(2) added predictive value and was retained in the regression up to 18 months post-CPX., Conclusions: These results indicate that commonly assessed CPX variables retain prognostic value for at least 2 years. The VE/VCO(2) slope is the superior predictor of adverse events throughout follow-up, although peak VO(2) provides additive prognostic information during the first 2 years of follow-up.

Background: The heart rate increase during exercise (DeltaHR) and heart rate recovery (HRR) have demonstrated prognostic value in several investigations, but its application in the heart failure (HF) population is limited, particularly in a beta-blocked (BB) cohort., Methods: Five-hundred and twenty subjects with HF underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO(2)), the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, DeltaHR and HRR at 1 min (HRR(1))., Results: There were 79 cardiac-related deaths during the tracking period. A HRR(1) threshold of or=16 beats/min was a significant prognostic marker in the overall group (hazard ratio: 4.6, 95% CI: 2.8-7.5, p<0.001) as well as no-BB (hazard ratio: 9.1, 95% CI: 4.1-20.2, p<0.001) and BB (hazard ratio: 2.9, 95% CI: 1.6-5.4, p<0.001) subgroups. The DeltaHR was a significant univariate predictor in the overall group and no-BB subgroup only. Multivariate Cox regression analysis revealed HRR(1) was the strongest prognostic marker (chi-square: 39.9, p<0.001). The VE/VCO(2) slope (residual chi-square: 21.8, p<0.001) and LVEF (residual chi-square: 9.6, p=0.002) were also retained in the regression., Conclusions: These results indicate that HRR maintains prognostic value in HF irrespective of BB use. The routine inclusion of HRR in the prognostic assessment of patients with HF may be warranted., (Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.)

Background: The lowest minute ventilation (VE) and carbon dioxide production (VCO(2)) ratio during exercise has been suggested to be the most stable and reproducible marker of ventilatory efficiency in patients with heart failure (HF). However, the prognostic power of this index is unknown., Methods and Results: A total of 847 HF patients underwent cardiopulmonary exercise testing (CPX) and were followed for 3 years. The associations between the lowest VE/VCO(2) ratio, maximal oxygen uptake (peak VO(2)), the VE/VCO(2) slope, and major events (death or transplantation) were evaluated using proportional hazards analysis; adequacy of the predictive models was assessed using Akaike information criterion (AIC) weights. There were 147 major adverse events. In multivariate analysis, the lowest VE/VCO(2) ratio (higher ratio associated with greater risk) was similar to the VE/VCO(2) slope in predicting risk (hazard ratios [HR] per unit increment 2.0, 95% CI 1.1-3.4, and 2.2, 95% CI 1.3-3.7, respectively; P < .01), followed by peak VO(2) (HR 1.6, 95% CI 1.1-2.4, P=.01). Patients exhibiting abnormalities for all 3 responses had an 11.6-fold higher risk. The AIC weight for the 3 variables combined (0.94) was higher than any single response or any combination of 2. The model including all 3 responses remained the most powerful after adjustment for beta-blocker use, type of HF, and after applying different cut points for high risk., Conclusions: The lowest VE/VCO(2) ratio adds to the prognostic power of conventional CPX responses in HF.

Background: Peak oxygen consumption (Vo(2)) is routinely assessed in patients with heart failure undergoing cardiopulmonary exercise testing. The purpose of the present investigation was to determine the prognostic ability of several established peak Vo(2) prediction equations in a large heart failure cohort., Methods and Results: One thousand one hundred sixty-five subjects (70% males; age, 57.0+/-13.8 years; ischemic etiology, 43%) diagnosed with heart failure underwent cardiopulmonary exercise testing. Percent-predicted peak Vo(2) was calculated according to normative values proposed by Wasserman and Hansen (equation), Jones et al (equation), the Cooper Clinic (below low fitness threshold), a Veteran's Administration male referral data set (4 equations), and the St James Take Heart Project for women (equation). The prognostic significance of percent-predicted Vo(2) values derived from the 2 latter, sex-specific equations were assessed collectively. There were 179 major cardiac events (117 deaths, 44 heart transplantations, and 18 left ventricular assist device implantations) during the 2-year tracking period (annual event rate, 10%). Measured peak Vo(2) and all percent-predicted peak Vo(2) calculations were significant univariate predictors of adverse events (chi(2)> or =31.9, P<0.001) and added prognostic value to ventilatory efficiency (VE/Vco(2) slope), the strongest cardiopulmonary exercise testing predictor of adverse events (chi(2)=150.7, P<0.001), in a multivariate regression. The Wasserman/Hansen prediction equation provided optimal prognostic information., Conclusions: Actual peak Vo(2) and the percent-predicted models included in this analysis all were significant predictors of adverse events. It seems that the percent-predicted peak Vo(2) value derived from the Wasserman/Hansen equations may outperform other expressions of this cardiopulmonary exercise testing variable.

Objective: The aim of this study is to evaluate the predictive accuracy of a cardiopulmonary exercise test (CPX) score., Background: Cardiopulmonary exercise test responses, including peak VO(2), markers of ventilatory inefficiency (eg, the VE/VCO(2) slope and oxygen uptake efficiency slope [OUES]), and hemodynamic responses, such as heart rate recovery (HRR) and chronotropic incompetence (CRI) are strong predictors of outcomes in patients with heart failure (HF). However, there is a need for simplified approaches that integrate the additive prognostic information from CPX., Methods: At 4 institutions, 710 patients with HF (568 male/142 female, mean age 56 +/- 13 years, resting left ventricular ejection fraction 33 +/- 14%) underwent CPX and were followed for cardiac-related mortality and separately for major cardiac events (death, hospitalization for HF, transplantation, left ventricular assist device implantation) for a mean of 29 +/- 25 months. The age-adjusted prognostic power of peak VO(2), VE/VCO(2) slope, OUES (VO(2) = a log(10)VE + b), resting end-tidal carbon dioxide pressure (PetCO(2)), HRR, and CRI were determined using Cox proportional hazards analysis, optimal cutpoints were determined, the variables were weighted, and a multivariate score was derived., Results: There were 175 composite outcomes. The VE/VCO(2) slope (> or =34) was the strongest predictor of risk and was attributed a relative weight of 7, with weighted scores for abnormal HRR (< or =6 beats at 1 minute), OUES (>1.4), PetCO(2) (<33 mm Hg), and peak VO(2) (< or =14 mL kg(-1) min(-1)) having scores of 5, 3, 3, and 2, respectively. Chronotropic incompetence was not a significant predictor and was excluded from the score. A summed score >15 was associated with an annual mortality rate of 27% and a relative risk of 7.6, whereas a score <5 was associated with a mortality rate of 0.4%. The composite score was the most accurate predictor of cardiovascular events among all CPX responses considered (concordance indexes 0.77 for mortality and 0.75 for composite outcome composed of mortality, transplantation, left ventricular assist device implantation, and HF-related hospitalization). The summed score remained significantly associated with increased risk after adjusting for age, gender, body mass index, ejection fraction, and cardiomyopathy type., Conclusion: A multivariable score based on readily available CPX responses provides a simple and integrated method that powerfully predicts outcomes in patients with HF.

Peak oxygen consumption (VO(2)) and ventilatory efficiency (minute ventilation/carbon dioxide output [VE/VCO(2)] slope) are prognostically important in heart failure (HF). The purpose of the present study was to compare the prognostic characteristics of these variables between Caucasian and African American patients. A total of 662 HF patients (455 Caucasian/207 African American) underwent cardiopulmonary exercise testing and were tracked for major cardiac events. The VE/VCO(2) slope was the strongest prognostic marker (chi-square >or=18.9, P<.001), irrespective of race. While peak VO(2) was a significant univariate predictor in both Caucasian (chi-square 42.0, P<.001) and African American (5.2, P=.02) subgroups, it was only retained in the Caucasian multivariate regression. The lack of predictive value of peak VO(2) in the African American subgroup was due to its lack of prognostic significance in female patients. While the VE/VCO(2) slope was the most robust prognostic marker in both Caucasian and African American patients, the predictive ability of peak VO(2) seems to be influenced by race and sex., ((c) 2008 Le Jacq)

Cardiopulmonary exercise testing (CPX) is an integral tool for assessing the clinical status and prognosis of patients with heart failure (HF). The present investigation examined differences in CPX variables and prognosis according to reason for test termination. One hundred eighty-three patients with HF (69% men, 31% women; mean age 53 +/- 13 years, left ventricular ejection fraction at rest 24.3 +/- 9.9%) underwent CPX in which the minute ventilation/carbon dioxide production slope, peak oxygen consumption, and peak respiratory exchange ratio were determined. Subjects were tracked for cardiac-related events for 2 years after CPX. Dyspnea and fatigue (general fatigue/leg fatigue) were the primary reasons for test termination in 79 and 104 patients, respectively. Peak oxygen consumption (15.4 +/- 5.7 vs 17.5 +/- 5.9 ml o(2) . kg(-1) . min(-1)) was significantly lower, whereas minute ventilation/carbon dioxide production slope (38.5 +/- 12.8 vs 33.9 +/- 9.8) was significantly higher in the dyspnea subgroup (p <0.05). There were 41 cardiac-related events during the 2-year tracking period. Patients with dyspnea were at significantly higher risk of adverse events (hazard ratio 2.1, 95% confidence interval 1.1 to 4.0, p = 0.02). In conclusion, these results indicate that patients with HF terminating an exercise test primarily because of dyspnea have an increased incidence of cardiac-related events and poorer CPX markers than those limited by fatigue.

Introduction: The minute ventilation carbon dioxide production (VE/VCO2) slope is a consistent and robust prognostic marker in the heart failure (HF) population. The purpose of this study was to assess the ability of the newly developed ventilatory classification system, a powerful predictor of major cardiac events (mortality, transplantation, and left ventricular assist device implantation), to identify varying degrees of risk for cardiac-related hospitalization., Methods: A total of 459 patients with chronic HF who underwent cardiopulmonary exercise testing were included in this analysis. The VE/VCO2 slope was determined, and participants were classified into 1 of 4 groups (ventilatory class [VC]-I: < or =29.9; VC-II: 30.0-35.9; VC-III: 36.0-44.9; and VC-IV: > or =45.0). Participants were tracked for cardiac-related hospitalization for 2 years following testing., Results: There were 169 cardiac-related hospitalizations during the 2-year tracking period (annual event rate = 21.6%). Decompensated HF, cardiac ischemia, and cardiac arrhythmia were the reasons for hospitalization in 83%, 11%, and 6% of the cases, respectively. Kaplan-Meier analysis revealed that the VC system was prognostically significant (log-rank = 85.2, P < .001) and superior to the Weber classification system (log-rank = 70.0, P < .001)., Discussion: This study indicates that the VC system, based on the VE/VCO2 slope, effectively identifies patients with HF at varying degrees of risk for cardiac-related hospitalization. Furthermore, this newly developed system prognostically outperformed the established Weber classification system based on peak oxygen uptake.

Background: Exercise oscillatory ventilation (EOV) occurs in a sub-group of patients with increased heart failure (HF) severity and poorer prognosis. The purpose of this investigation was to examine the prognostic value of the largest ventilatory oscillation characteristics in HF patients., Methods: One hundred fifty-four subjects diagnosed with HF underwent cardiopulmonary exercise testing. Subjects with EOV were then divided into two sub-groups: (1) largest ventilatory oscillation during the first half of exercise with an oscillation width > or =30 seconds; and (2) largest ventilatory oscillation during the second half of exercise or an oscillation width <30 seconds. Subjects were tracked for major cardiac events after the exercise test., Results: The fifty-five subjects (35.7%) in the overall group demonstrating EOV during the exercise test were at significantly higher risk for adverse events (hazard ratio = 3.0, 95% confidence interval 1.6 to 5.5, p < 0.001). The prognostic value of this ventilatory phenomenon improved when only subjects with the largest ventilatory oscillation during the first half of exercise with an oscillation width > or =30 seconds were defined as having EOV (hazard ratio = 3.6, 95% confidence interval 1.6 to 7.9, p = 0.002)., Conclusions: In this study we found that the characteristics of the largest oscillatory ventilation provide valuable prognostic information in patients with EOV.

Purpose: The analysis of oxygen (O2) uptake on-kinetics at the onset of aerobic exercise has been shown to be reflective of cardiovascular and skeletal muscle health in a number of previous investigations. The purpose of the present investigation is to assess the short-term reliability of O2 uptake on-kinetics in a group of apparently healthy individuals., Methods: Forty apparently healthy subjects participated in 3 consecutive treadmill exercise sessions on 3 consecutive days. During each session, O2 uptake was collected at rest for 2 minutes and during ambulation at 2.2 miles per hour and a 6% grade for 6 minutes. The time constant (TC) for the O2 uptake response was calculated for each of the 3 sessions using the equation: O2(t) = O2(resting) + O2(steady-rate)[1 - e]., Results: Two subjects did not adhere to the physical activity guidelines and were excluded from data analysis. The following data are representative of the remaining 38 subjects. The mean O2 uptake TC value for the 3 sessions was 33.67 +/- 7.87, 34.59 +/- 7.57, and 32.59 +/- 6.64 seconds, respectively. The intraclass correlation coefficient for the O2 uptake TC was 0.84 (P < .001)., Conclusions: The results of the present study indicate O2 uptake on-kinetics may be reliably measured using a single testing session. Multiple testing sessions, which would limit the potential clinical application of O2 uptake on-kinetics, may therefore not be necessary. Future research should be directed toward determining if O2 uptake on-kinetics is equally reliable in patient populations.

Background: Cardiopulmonary exercise testing (CPET) variables provide valuable prognostic information in the heart failure (HF) population. The purpose of the present study is to assess the ability of resting end-tidal carbon dioxide partial pressure (PETCO2) to predict cardiac-related events in patients with HF., Methods: 121 subjects diagnosed with compensated HF underwent CPET on an outpatient basis. Mean age and ejection fraction were 49.3 years (+/-14.7) and 28.4% (+/-13.4), respectively. Resting P(ET)CO2 was determined immediately prior to the exercise test in the seated position. Peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production (VE/VCO2) slope were also acquired during CPET., Results: There were 41 cardiac-related hospitalizations and 9 cardiac-related deaths in the year following CPET. Mean resting P(ET)CO2, peak VO2 and VE/VCO2 slope were 34.1 mmHg (+/-4.6), 14.5 ml*kg(-1)*min(-1) (+/-5.1) and 35.9 (+/-8.7) respectively. Univariate Cox regression analysis revealed that resting P(ET)CO2 (Chi-square=28.4, p<0.001), peak VO2 (Chi-square=21.6, p<0.001) and VE/VCO2 slope (Chi-square=54.9, p<0.001) were all significant predictors of cardiac related events. Multivariate Cox regression analysis revealed resting P(ET)CO2 added to the prognostic value of VE/VCO2 slope in predicting cardiac related events (residual Chi-square=4.4, p=0.04). Peak VO2 did not add additional value and was removed (residual Chi-square=3.2, p=0.08)., Conclusions: These results indicate a resting ventilatory expired gas variable possesses prognostic value independently and in combination with an established prognostic marker from the CPET. Resting P(ET)CO2 may therefore be a valuable objective measure to obtain during both non-exercise and exercise evaluations in patients with HF.

Background: Cardiopulmonary exercise testing (CPET) is considered a standard of care in heart failure (HF). The impact that duration of time post-evaluation has on the prognostic value of CPET, however, has not been explored. The purpose of this investigation was to examine the ability of peak oxygen consumption (VO(2)) and the minute ventilation-carbon dioxide production (VE/VCO(2)) slope to predict cardiac-related events at different time intervals post CPET., Methods: Two hundred fifty-eight subjects diagnosed with HF underwent CPET. The ability of peak VO(2) and VE/VCO(2) slope to predict cardiac-related events without a time limit, one year post CPET and greater than one year post CPET was examined., Results: Both peak VO(2) and VE/VCO(2) slope were significant predictors of cardiac-related mortality and hospitalization during the no time constraint and one year post CPET tracking scenarios (Hazard Ratio Range: 3.5-12.4, p<0.001). Peak VO(2) was no longer a significant predictor of mortality greater than one year post CPET. Generally, as time following CPET surpassed one year, the prognostic sensitivity of both variables slightly increased ( approximately 5%) while specificity sharply decreased ( approximately 20%)., Conclusions: Both peak VO(2) and VE/VCO(2) slope are significant predictors of cardiac-related events in HF. However, the prognostic characteristics of these variables following CPET appear to be time-sensitive.

Background: The minute ventilation-carbon dioxide production (VE/VCO2) slope, obtained during exercise testing, possesses prognostic value in heart failure (HF). The VE-VCO2 relationship is generally linear thereby hypothetically producing similar slope values regardless of the exercise-test time interval used for calculation., Design: This study assesses the ability of the VE/VCO2 slope, calculated at different time intervals throughout a progressive exercise test, to predict 1-year cardiac-related hospitalization and mortality in subjects with HF., Methods: Seventy-two subjects underwent symptom-limited exercise testing with ventilatory expired gas analysis. Mean age and left ventricular ejection fraction for 44 male and 28 female subjects were 51.2 years (+/-13.0) and 27.0% (+/-12.3) respectively. The VE/VCO2 slope was calculated from time 0 to 25, 50, 75 and 100% of exercise time and subsequently used to create five randomly selected VE/VCO2 slope categories., Results: (The intraclass correlation coefficient found calculation of the VE/VCO2 slope, when divided into quartiles, to be a reliable measure (alpha=0.94, P<0.0001). Univariate Cox regression analysis revealed all VE/VCO2 slope categories (25-100% and random selections) were significant predictors of cardiac-related hospitalization and mortality over a 1-year period. Multivariate Cox regression analysis revealed all VE/VCO2 slope categories outperformed peak oxygen consumption (VO2) in predicting hospitalization and mortality at 1 year., Conclusions: Although the different classification schemes were not identical, these results suggest VE/VCO2 slope maintains prognostic significance regardless of exercise-test time interval. Calculation of VE/VCO2 slope may therefore still be valuable in subjects putting forth a sub-maximal effort while effort-dependent measures, such as peak VO2, are not.

Purpose: A significant discrepancy between measured oxygen consumption (VO(2)) (via ventilatory expired gas analysis) and estimated VO(2) (via the imposed workload) frequently is reported in the heart failure (HF) population during symptom-limited exercise testing. The purpose of this investigation was to examine the difference between measured and estimated VO(2) (VO(2) discrepancy) during a highly conservative ramping protocol., Methods: For this study, 28 subjects with compensated HF (20 men and 8 women; age, 51.1 +/- 14.6 years) and 19 healthy control subjects (age-, gender-, and activity-matched to an HF subgroup) underwent symptom-limited exercise testing (treadmill) with ventilatory expired gas analysis., Results: Peak estimated and measured VO(2) values were significantly higher in the age-, gender-, and activity-matched control group than in the HF group, but the change in measured VO(2) per change in estimated VO(2) (Deltameasured/Deltaestimated VO(2) slope) and the VO(2) discrepancy did not reach statistical significance. Peak estimated VO(2) was a significant predictor of peak measured VO(2) in the overall HF group (R2 = 0.90; P <.001)., Conclusions: Although estimated VO(2) is not considered a replacement for measured VO(2), these results indicate that a highly conservative exercise protocol may allow for a more accurate prediction of peak measured VO(2) via the estimated oxygen cost for a given workload in patients with compensated HF.

Purpose: The analysis of oxygen (O(2)) uptake on-kinetics during steady-rate is gaining interest in the heart failure (HF) population. The rate change in O(2) at the initiation of exercise can be assessed via nonlinear regression time constant (TC) or an algebraic equation (mean response time [MRT]). These calculations are presumed to be interchangeable, but research supporting this claim is limited. This investigation compares and contrasts two of the more commonly used O(2) uptake on-kinetic calculations., Method: Twenty-eight subjects diagnosed with compensated HF and 19 age, sex, and activity-matched controls underwent a symptom-limited exercise test and a steady-rate exercise session (6 min). Peak O(2) uptake, O(2) uptake at ventilatory threshold, the O(2) uptake TC (TC), and the O(2) uptake mean response time (MRT) were calculated for each subject., Results: O(2) uptake on-kinetics was significantly faster for the control group ( < 0.05) regardless of calculation method. There was a significant difference between the O(2) uptake TC and MRT for the HF group. All O(2) uptake on-kinetic calculations were significantly correlated with aerobic capacity., Conclusions: O(2) uptake TC and MRT values may not be interchangeable in the HF population. All O(2) uptake on-kinetic calculations did produce a significant difference between experimental and control groups and correlated with indicators of aerobic capacity. The 10-s O(2) uptake on-kinetic calculations may be preferable secondary to expired gas fluctuations associated with breath-by-breath measures. Further work is, however, needed to determine which averaged O(2) uptake on-kinetic expression is optimal given the significant difference between TC and MRT. A mechanism for this difference may be the oscillatory ventilatory expired gas pattern demonstrated by some patients with HF.

Heart disease is a major cause of morbidity and mortality in the United States, with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo an exercise electrocardiogram (ECG) and/ or imaging study as a first-line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently, CPX has been used to detect exercise-induced myocardial ischemia (EIMI) suggestive of underlying CAD. Two CPX variables, oxygen pulse (VO2/HR) and the slope of oxygen consumption versus work rate (ΔVO2/ ΔWR), have been identified to be especially indicative of EIMI. Currently, there are a number of diagnostic tests available for the identification of CAD, with the most widely used being stress ECG, stress myocardial perfusion imaging (MPI) and echocardiography, and cardiac catheterization. Exercise ECG, although inexpensive, has a number of well-recognized limitations, including low sensitivity resulting in false-negative results. Stress (exercise or pharmaceutically induced) MPI and catheterization are more accurate but also more invasive and expensive. It appears that CPX may improve the diagnostic accuracy of exercise ECG. This review will address the potential utility of CPX in patients with suspected or confirmed myocardial ischemia. [ABSTRACT FROM PUBLISHER]

Abstract: The purpose of this investigation was to examine the ability of heart rate recovery (HRR) to predict mortality secondary to pump failure or sudden cardiac death (SCD) in patients with heart failure (HF). Kaplan–Meier analysis revealed a significant difference in survival for both SCD (100% vs. 73.9%, log-rank: 50.5, p <0.001) and pump failure (96.1% vs. survival=78.4%, log-rank: 24.4, p <0.001) endpoints according to a

Abstract: Background: The Weber classification system is a well established method for categorizing patients according to peak oxygen consumption (VO2), but it is unknown whether ventilatory efficiency adds prognostic value. The purpose of the current study was to assess the added prognostic value of the minute ventilation/carbon dioxide production (VE/VCO2) slope to the Weber classification system in patients diagnosed with heart failure (HF). Methods: Five hundred and forty-eight subjects with HF participated in this analysis. Mean left ventricular ejection fraction was 32.9±13.3%. Subjects were tracked for cardiac-related mortality following the exercise test. Results: The numbers of subjects in Weber Classes A–D were 144, 119, 212 and 71, respectively. One hundred and eight major cardiac events (91 deaths, 10 emergent heart transplants and 7 LVAD implantations) occurred during a mean tracking period of 33.8±28.6 months. Receiver operating characteristic (ROC) curve analysis revealed the VE/VCO2 slope prognostic classification schemes were significant in each of the four Weber classes (A: area=0.84, optimal threshold=31.3, 79% sensitivity/90% specificity, p <0.01; B: area=0.66, optimal threshold=33.9, 73% sensitivity/67% specificity, p <0.05; C: area=0.71, optimal threshold=36.0, 65% sensitivity/68% specificity, p <0.01; D: area=0.66, optimal threshold=41.8, 68% sensitivity/58% specificity, p <0.05). Conclusions: These results indicate that the VE/VCO2 slope improves the identification of individuals at higher risk for mortality within each Weber class. These findings further support the routine clinical application of ventilatory efficiency in the HF population. [Copyright &y& Elsevier]