Erin West

Impact of Cardiorespiratory Fitness on the Obesity Paradox in Patients With Heart Failure

OBJECTIVE To determine the impact of cardiorespiratory fitness (FIT) on survival in relation to the obesity paradox in patients with systolic heart failure (HF). PATIENTS AND METHODS We studied 2066 patients with systolic HF (body mass index [BMI] ≥18.5 kg/m(2)) between April 1, 1993 and May 11, 2011 (with 1784 [86%] tested after January 31, 2000) from a multicenter cardiopulmonary exercise testing database who were followed for up to 5 years (mean ± SD, 25.0±17.5 months) to determine the impact of FIT (peak oxygen consumption <14 vs ≥14 mL O2 ∙ kg(-1) ∙ min(-1)) on the obesity paradox. RESULTS There were 212 deaths during follow-up (annual mortality, 4.5%). In patients with low FIT, annual mortality was 8.2% compared with 2.8% in those with high FIT (P<.001). After adjusting for age and sex, BMI was a significant predictor of survival in the low FIT subgroup when expressed as a continuous (P=.03) and dichotomous (<25.0 vs ≥25.0 kg/m(2)) (P=.01) variable. Continuous and dichotomous BMI expressions were not significant predictors of survival in the overall and high FIT groups after adjusting for age and sex. In patients with low FIT, progressively worse survival was noted with BMI of 30.0 or greater, 25.0 to 29.9, and 18.5 to 24.9 (log-rank, 11.7; P=.003), whereas there was no obesity paradox noted in those with high FIT (log-rank, 1.72; P=.42). CONCLUSION These results indicate that FIT modifies the relationship between BMI and survival. Thus, assessing the obesity paradox in systolic HF may be misleading unless FIT is considered.

Determining the Preferred Percent-Predicted Equation for Peak Oxygen Consumption in Patients With Heart Failure

Background—Peak oxygen consumption (Vo2) 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 Vo2 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 Vo2 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 Vo2 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 Vo2 and all percent-predicted peak Vo2 calculations were significant univariate predictors of adverse events (&khgr;2≥31.9, P<0.001) and added prognostic value to ventilatory efficiency (VE/Vco2 slope), the strongest cardiopulmonary exercise testing predictor of adverse events (&khgr;2=150.7, P<0.001), in a multivariate regression. The Wasserman/Hansen prediction equation provided optimal prognostic information. Conclusions—Actual peak Vo2 and the percent-predicted models included in this analysis all were significant predictors of adverse events. It seems that the percent-predicted peak Vo2 value derived from the Wasserman/Hansen equations may outperform other expressions of this cardiopulmonary exercise testing variable.

Influence of Etiology of Heart Failure on the Obesity Paradox

Several investigations have demonstrated that higher body weight, as assessed by the body mass index, is associated with improved prognosis in patients with heart failure (HF). The purpose of the present investigation was to assess the influence of HF etiology on the prognostic ability of the body mass index in a cohort undergoing cardiopulmonary exercise testing. A total of 1,160 subjects were included in the analysis. All subjects underwent cardiopulmonary exercise testing, at which the minute ventilation/carbon dioxide production slope and peak oxygen consumption were determined. In the overall group, 193 cardiac deaths occurred during a mean follow-up of 30.7 +/- 25.6 months (annual event rate 6.0%). The subjects classified as obese consistently had improved survival compared to those classified as normal weight (overall survival rate 88.0% vs <or=81.1%, p <0.001). Differences in survival according to HF etiology were observed for those classified as overweight. In the ischemic subgroup, the survival characteristics for the overweight subjects (75.5%) were similar those for subjects classified as normal weight (81.1%). The converse was true for the nonischemic subgroup, for whom the survival trends for the obese (86.4%) and overweight subjects (88.4%) were similar. The minute ventilation/carbon dioxide production slope was the strongest prognostic marker (chi-square >or=43.4, p <0.001) for both etiologies, and the body mass index added prognostic value (residual chi-square >or=4.7, p <0.05). In conclusion, these results further support the notion that obesity confers improved prognosis in patients with HF, irrespective of the HF etiology. Moreover, the body mass index appears to add predictive value during the cardiopulmonary exercise testing assessment. However, survival appears to differ according to HF etiology in subjects classified as overweight.

Validation of a Cardiopulmonary Exercise Test Score in Heart Failure

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.

E/e' Ratio in Patients with Unexplained Dyspnea: Lack of Accuracy in Estimating Left Ventricular Filling Pressure

Background— Elevated left ventricular filling pressure is a cardinal feature of heart failure with preserved ejection fraction. Mitral E/e′ ratio has been proposed as a noninvasive measure of left ventricular filling pressure. We studied the accuracy of E/e′ to estimate and track changes of left ventricular filling pressure in patients with unexplained dyspnea. Methods and Results— We performed supine and upright transthoracic echocardiography in 118 patients with unexplained dyspnea who underwent right heart catheterization. Supine E/e′ ratio modestly but significantly correlated with supine pulmonary arterial wedge pressure (PAWP; r =0.36; P <0.001) and demonstrated poor agreement with PAWP values (Bland–Altman limits of agreement of −8.3 to 8.3 mm Hg; range, 6.5–21.2 mm Hg). Similarly, E/e′ ratio cut off of 13 performed poorly in identifying patients with elevated left ventricular filling pressure (sensitivity 6%, specificity 90%). The receiver-operating characteristic area of E/e′ was 0.65 (95% confidencce interval, 0.50–0.79). With change from the supine to upright position, PAWP decreased (−5±4 mm Hg; P <0.001) as did both E wave (−17±15 cm/s; P <0.001) and e′ (−2.7±2.7 cm/s; P <0.001) velocities, whereas E/e′ remained stable (+0.2±2.6; P =0.57). Positional change in PAWP correlated modestly with change in E-wave ( r =0.37; P <0.001) velocity. There was no appreciable relationship between change in PAWP and change in average E/e′ ( r =−0.04; P =0.77) and in half the patients the change in PAWP and E/e′ were directionally opposite. Conclusions— In patients with unexplained dyspnea, E/e′ ratio neither accurately estimates PAWP nor identifies patients with elevated PAWP consistent with heart failure with preserved ejection fraction. Positional changes in E/e′ ratio do not reflect changes in PAWP.Background—Elevated left ventricular filling pressure is a cardinal feature of heart failure with preserved ejection fraction. Mitral E/e′ ratio has been proposed as a noninvasive measure of left ventricular filling pressure. We studied the accuracy of E/e′ to estimate and track changes of left ventricular filling pressure in patients with unexplained dyspnea. Methods and Results—We performed supine and upright transthoracic echocardiography in 118 patients with unexplained dyspnea who underwent right heart catheterization. Supine E/e′ ratio modestly but significantly correlated with supine pulmonary arterial wedge pressure (PAWP; r=0.36; P<0.001) and demonstrated poor agreement with PAWP values (Bland–Altman limits of agreement of −8.3 to 8.3 mm Hg; range, 6.5–21.2 mm Hg). Similarly, E/e′ ratio cut off of 13 performed poorly in identifying patients with elevated left ventricular filling pressure (sensitivity 6%, specificity 90%). The receiver-operating characteristic area of E/e′ was 0.65 (95% confidencce interval, 0.50–0.79). With change from the supine to upright position, PAWP decreased (−5±4 mm Hg; P<0.001) as did both E wave (−17±15 cm/s; P<0.001) and e′ (−2.7±2.7 cm/s; P<0.001) velocities, whereas E/e′ remained stable (+0.2±2.6; P=0.57). Positional change in PAWP correlated modestly with change in E-wave (r=0.37; P<0.001) velocity. There was no appreciable relationship between change in PAWP and change in average E/e′ (r=−0.04; P=0.77) and in half the patients the change in PAWP and E/e′ were directionally opposite. Conclusions—In patients with unexplained dyspnea, E/e′ ratio neither accurately estimates PAWP nor identifies patients with elevated PAWP consistent with heart failure with preserved ejection fraction. Positional changes in E/e′ ratio do not reflect changes in PAWP.

Effects of Respiratory Exchange Ratio on the Prognostic Value of Peak Oxygen Consumption and Ventilatory Efficiency in Patients With Systolic Heart Failure

OBJECTIVES The purpose of this analysis was to evaluate the prognostic characteristics of peak oxygen consumption (Vo2) and the minute ventilation/carbon dioxide (VE/Vco2) slope of different peak respiratory exchange ratios (RERs) obtained from cardiopulmonary exercise testing in patients with heart failure (HF). BACKGROUND For patients with HF, peak Vo2 and the VE/Vco2 slope are used for assessing prognosis. Peak Vo2 is assessed in association with peak RER ≥1.10, indicating maximal effort and prognostic sensitivity. Conversely, the VE/Vco2 slope provides effort-independent prognostic discrimination. METHODS Patients with HF scheduled to undergo cardiopulmonary exercise testing were enrolled. Patients were subclassified by peak RER (RER <1.00, RER 1.00 to 1.04, RER 1.05 to 1.09, RER ≥1.10) and followed for up to 3 years for major cardiac-related events (death, left ventricular assist device implantation, or cardiac transplantation). RESULTS Included were 1,728 patients with HF (75% males; 40% ischemic etiology; age: 55 ± 14 years; left ventricular ejection fraction: 28 ± 10%). Two hundred seventy major events occurred, with no proportional differences across the RER subgroups. Multivariate Cox regression analysis indicated that the VE/Vco2 slope and peak Vo2 remained prognostic within each subgroup; the VE/Vco2 slope remained the strongest predictor. Receiver-operating characteristic analysis demonstrated equitable prognostic cutoffs for the VE/Vco2 slope (range: 34.9 to 35.7; area under the curve [AUC] range: 0.69 to 0.75) and peak Vo2 (range: 13.8 to 14.0 ml·kg(-1)·min(-1); AUC range: 0.68 to 0.75). CONCLUSIONS Peak Vo2 provided a sensitive assessment of prognosis in patients with HF in all RER subgroups. The VE/Vco2 slope provided greater prognostic discrimination in all RER subgroups. Clinical consideration may be warranted for patients with low RER, low peak Vo2, and an elevated VE/Vco2 slope.

Heart Failure and Midrange Ejection Fraction Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes

Background— Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. Methods and Results— We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF 55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9–5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13–0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15–0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. Conclusions— Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.Background—Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. Methods and Results—We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%–55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9–5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13–0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15–0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. Conclusions—Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.

Ventilatory Power: A Novel Index that Enhances Prognostic Assessment of Patients with Heart Failure

Background—Minute ventilation/CO2 production (VE/VCO2) 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/VCO2 slope has many applications, including utility as a well-validated prognostic gauge for patients with heart failure (HF). In this study, we combine VE/VCO2 slope with systolic blood pressure, creating a novel index that we labeled ventilatory power. Ventilatory power links the combined physiology inherent in the VE/VCO2 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/VCO2 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.Background— Minute ventilation/CO2 production (VE/Vco2) 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/Vco2 slope has many applications, including utility as a well-validated prognostic gauge for patients with heart failure (HF). In this study, we combine VE/Vco2 slope with systolic blood pressure, creating a novel index that we labeled ventilatory power. Ventilatory power links the combined physiology inherent in the VE/Vco2 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/Vco2 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.

A neural network approach to predicting outcomes in heart failure using cardiopulmonary exercise testing

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.

Left ventricular deformation at rest predicts exercise-induced elevation in pulmonary artery wedge pressure in patients with unexplained dyspnoea.

Impaired left ventricular (LV) deformation despite preserved LV ejection fraction (LVEF) is common and predicts outcomes in heart failure with preserved LVEF. We hypothesized that impaired LV deformation at rest is a marker of impaired cardiac systolic and diastolic reserve, and aimed to determine whether resting longitudinal (LS) and circumferential strain (CS) are associated with invasively measured haemodynamic response to exercise in patients with dyspnoea and a normal LVEF.