Prognostic Value of Cardiopulmonary Exercise Testing in Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction

Abstract

Background: This study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF).

Methods and results: In 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40-49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76 [0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome, Pinteraction=0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06-1.17] versus 1.04 [1.03-1.06], respectively for the composite outcome, Pinteraction=0.012; 1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization, Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively), while only peak VO2 was related to HF hospitalization (0.81 [0.72-0.92]). In HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value beyond clinical variables based on the C-statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value.

Conclusions: Both peak VO2 and VE/VCO2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF.

Keywords: cardiopulmonary exercise testing; ejection fraction; heart failure; oxygen consumption; preserved ejection fraction.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Adjusted incidence rates of the composite outcome and heart failure hospitalization according to peak VO 2 and VE/VCO 2 slope in HFrEF, HFmEF, and HFpEF participants. All analyses were adjusted for age, sex, ejection fraction, chronic kidney disease, resting heart rate, resting systolic blood pressure, and coronary artery disease. Dashed lines indicate the 95% confidence intervals. HF indicates heart failure; HFmEF, HF with midrange ejection fraction; HFpEF, HF with preserved ejection fraction; HFrEF, HF with reduced ejection fraction; VE/VCO 2, minute ventilation–carbon dioxide production relationship; VO 2, oxygen consumption.

Figure 2

Unadjusted incidence rates of the studied outcomes in HFrEF, HFmEF, and HFpEF patients categorized according to presence of abnormalities in CPET measures. Abnormalities in CPET measures were considered as follows: Peak VO 2 <14 mL/min per kg or VE/VCO 2 slope >30. CPET indicates cardiopulmonary exercise testing; HF, heart failure; HFmEF, HF with midrange ejection fraction; HFpEF, HF with preserved ejection fraction; HFrEF, HF with reduced ejection fraction; PY, patient‐years; VE/VCO 2, minute ventilation–carbon dioxide production relationship; VO 2, oxygen consumption.