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

• Published in: The American heart journal 2020-02, Vol.220, p.97-107
• Main Authors: Fudim, Marat, Kelly, Jacob P., Jones, Aaron D., AbouEzzeddine, Omar F., Ambrosy, Andrew P., Greene, Stephen J., Reddy, Yogesh N.V., Anstrom, Kevin J., Alhanti, Brooke, Lewis, Gregory D., Hernandez, Adrian F., Felker, G. Michael
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers; Biomarkers - blood; Brain natriuretic peptide; Cardiorespiratory Fitness; Chronic Disease; Clinical outcomes; Clinical trials; Congestive heart failure; Differentiation; Female; Galectin 3 - blood; Galectin-3; Growth Differentiation Factor 15 - blood; Heart failure; Heart Failure - blood; Heart Failure - physiopathology; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein - blood; Iron; Laboratories; Male; Middle Aged; Natriuretic Peptide, Brain - blood; Patients; Peptide Fragments - blood; Physical fitness; Risk analysis; Risk factors; Stroke Volume - physiology; Time Factors; Vanadium oxides; Variables; Walk Test
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2019.11.006

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. 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. 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