Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure?

Marat Fudim, Jacob P Kelly, Aaron D Jones, Omar F AbouEzzeddine, Andrew P Ambrosy, Stephen J Greene, Yogesh N V Reddy, Kevin J Anstrom, Brooke Alhanti, Gregory D Lewis, Adrian F Hernandez, G Michael Felker, Marat Fudim, Jacob P Kelly, Aaron D Jones, Omar F AbouEzzeddine, Andrew P Ambrosy, Stephen J Greene, Yogesh N V Reddy, Kevin J Anstrom, Brooke Alhanti, Gregory D Lewis, Adrian F Hernandez, G Michael Felker

Abstract

Background: Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time.

Methods: This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3.

Results: Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726 mL/min/kg per doubling, 95% CI -1.100 to -0.353, P < .001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606 m per doubling, 95% CI -61.404 to -1.809, P = .038).

Conclusions: In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP.

Trial registration: ClinicalTrials.gov NCT00763867.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
CONSORT diagram
Figure 2.
Figure 2.
Correlation Between Baseline Peak VO2 and Baseline Biomarkers by HF Type in HFrEF and HFpEF
Figure 3:
Figure 3:
Functional Capacity Change vs. Biomarker Change by Heart Failure Type. (A) HFrEF (IRONOUT Trial), Change from Baseline to 16 Weeks Post-Baseline; (B) HFpEF (RELAX Trial, Change from Baseline to 24 Weeks Post-Baseline
Figure 3:
Figure 3:
Functional Capacity Change vs. Biomarker Change by Heart Failure Type. (A) HFrEF (IRONOUT Trial), Change from Baseline to 16 Weeks Post-Baseline; (B) HFpEF (RELAX Trial, Change from Baseline to 24 Weeks Post-Baseline
Figure 4.
Figure 4.
Multivariable Association of Biomarker Change with Functional Capacity Change by HF Type with Placebo Group Sensitivity Analysis
Central Figure:
Central Figure:
Review of Results

Source: PubMed

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