PMID- 31805424 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20211204 IS - 1097-6744 (Electronic) IS - 0002-8703 (Print) IS - 0002-8703 (Linking) VI - 220 DP - 2020 Feb TI - Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure? PG - 97-107 LID - S0002-8703(19)30307-2 [pii] LID - 10.1016/j.ahj.2019.11.006 [doi] 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 VO(2), VE/VCO(2) 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/VCO(2) slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO(2) 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. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Fudim, Marat AU - Fudim M AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC; Division of Cardiology, Duke University Medical Center, Durham, NC. Electronic address: marat.fudim@duke.edu. FAU - Kelly, Jacob P AU - Kelly JP AD - Heart and Vascular Institute, Anchorage, AL. FAU - Jones, Aaron D AU - Jones AD AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC. FAU - AbouEzzeddine, Omar F AU - AbouEzzeddine OF AD - Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. FAU - Ambrosy, Andrew P AU - Ambrosy AP AD - Division of Research, Kaiser Permanente Northern California, Oakland, CA. FAU - Greene, Stephen J AU - Greene SJ AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC; Division of Cardiology, Duke University Medical Center, Durham, NC. FAU - Reddy, Yogesh N V AU - Reddy YNV AD - Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. FAU - Anstrom, Kevin J AU - Anstrom KJ AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC. FAU - Alhanti, Brooke AU - Alhanti B AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC. FAU - Lewis, Gregory D AU - Lewis GD AD - Division of Cardiology, Massachusetts General Hospital, Boston, MA. FAU - Hernandez, Adrian F AU - Hernandez AF AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC; Division of Cardiology, Duke University Medical Center, Durham, NC. FAU - Felker, G Michael AU - Felker GM AD - Duke Clinical Research Institute and Division of Cardiology, Durham, NC; Division of Cardiology, Duke University Medical Center, Durham, NC. LA - eng SI - ClinicalTrials.gov/NCT00763867 GR - T32 HL079896/HL/NHLBI NIH HHS/United States GR - UL1 TR002548/TR/NCATS NIH HHS/United States GR - U10 HL110342/HL/NHLBI NIH HHS/United States GR - T32 HL007101/HL/NHLBI NIH HHS/United States GR - U10 HL084904/HL/NHLBI NIH HHS/United States GR - U10 HL110312/HL/NHLBI NIH HHS/United States GR - U10 HL110262/HL/NHLBI NIH HHS/United States GR - T32 HL069749/HL/NHLBI NIH HHS/United States GR - U10 HL110337/HL/NHLBI NIH HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States GR - U10 HL110309/HL/NHLBI NIH HHS/United States GR - U10 HL110336/HL/NHLBI NIH HHS/United States GR - U10 HL110338/HL/NHLBI NIH HHS/United States GR - U10 HL110302/HL/NHLBI NIH HHS/United States GR - U10 HL110297/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20191116 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Biomarkers) RN - 0 (Blood Proteins) RN - 0 (GDF15 protein, human) RN - 0 (Galectin 3) RN - 0 (Galectins) RN - 0 (Growth Differentiation Factor 15) RN - 0 (IL1RL1 protein, human) RN - 0 (Interleukin-1 Receptor-Like 1 Protein) RN - 0 (LGALS3 protein, human) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM MH - Aged MH - Biomarkers/blood MH - Blood Proteins MH - *Cardiorespiratory Fitness MH - Chronic Disease MH - Female MH - Galectin 3/*blood MH - Galectins MH - Growth Differentiation Factor 15/*blood MH - Heart Failure/*blood/physiopathology MH - Humans MH - Interleukin-1 Receptor-Like 1 Protein/*blood MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/*blood MH - Peptide Fragments/*blood MH - Stroke Volume/physiology MH - Time Factors MH - Walk Test PMC - PMC7008085 MID - NIHMS1543660 EDAT- 2019/12/06 06:00 MHDA- 2020/04/24 06:00 PMCR- 2021/02/01 CRDT- 2019/12/06 06:00 PHST- 2019/11/12 00:00 [received] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/12/06 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] PHST- 2019/12/06 06:00 [entrez] PHST- 2021/02/01 00:00 [pmc-release] AID - S0002-8703(19)30307-2 [pii] AID - 10.1016/j.ahj.2019.11.006 [doi] PST - ppublish SO - Am Heart J. 2020 Feb;220:97-107. doi: 10.1016/j.ahj.2019.11.006. Epub 2019 Nov 16.