TY - JOUR
T1 - Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure?
AU - Fudim, Marat
AU - Kelly, Jacob P.
AU - Jones, Aaron D.
AU - AbouEzzeddine, Omar F.
AU - Ambrosy, Andrew P.
AU - Greene, Stephen J.
AU - Reddy, Yogesh N.V.
AU - Anstrom, Kevin J.
AU - Alhanti, Brooke
AU - Lewis, Gregory D.
AU - Hernandez, Adrian F.
AU - Felker, G. Michael
N1 - Funding Information:
Conflict of interest: M. F. is supported by American Heart Association grant 17MCPRP33460225 and National Institutes of Health T32 grant 5T32HL007101. S. J. G. is supported by a National Institutes of Health T32 postdoctoral training grant (5T32HL069749) and a Heart Failure Society of America/ Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis. M. V. is supported by a National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL007604). All other authors declare no relevant financial disclosures.The research reported in this publication was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number U10 HL084904 (for the Coordinating Center) and award numbers U10 HL110297, U10 HL110342, U10 HL110309, U10 HL110262, U10 HL110338, U10 HL110312, U10 HL110302, U10 HL110336, and U10 HL110337 (for the Regional Clinical Centers). Database management and statistical analyses were performed by the Duke Clinical Research Institute (Durham, NC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH/NHLBI.
Funding Information:
The research reported in this publication was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number U10 HL084904 (for the Coordinating Center) and award numbers U10 HL110297 , U10 HL110342 , U10 HL110309 , U10 HL110262 , U10 HL110338 , U10 HL110312 , U10 HL110302 , U10 HL110336 , and U10 HL110337 (for the Regional Clinical Centers). Database management and statistical analyses were performed by the Duke Clinical Research Institute (Durham, NC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH/NHLBI. Appendix A
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ahj.2019.11.006
DO - 10.1016/j.ahj.2019.11.006
M3 - Article
C2 - 31805424
AN - SCOPUS:85075712351
SN - 0002-8703
VL - 220
SP - 97
EP - 107
JO - American Heart Journal
JF - American Heart Journal
ER -