Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy

Ravi B. Patel; Fawaz Alenezi; Jie Lena Sun; Brooke Alhanti; Muthiah Vaduganathan; Jae K. Oh; Margaret M. Redfield; Javed Butler; Adrian F. Hernandez; Eric J. Velazquez; Sanjiv J. Shah

doi:10.1016/j.cardfail.2019.12.001

Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy

Ravi B. Patel^*, Fawaz Alenezi, Jie Lena Sun, Brooke Alhanti, Muthiah Vaduganathan, Jae K. Oh, Margaret M. Redfield, Javed Butler, Adrian F. Hernandez, Eric J. Velazquez, Sanjiv J. Shah

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Although left atrial (LA) mechanical dysfunction in heart failure with preserved ejection fraction (HFpEF) is associated with poor clinical outcomes, the influence of LA myopathy on temporal changes in cardiovascular biomarkers is unclear. Methods and Results: We evaluated biomarker correlates of LA myopathy, as defined by reduced LA strain, and the associations of LA strain with longitudinal changes in biomarkers among participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. LA speckle-tracking was performed on baseline echocardiograms of RELAX participants to measure LA reservoir and LA contractile strain. Of the 216 RELAX participants, 169 (78%) had measurable LA strain and biomarker data. Participants with LA reservoir strain below median (13.5%, interquartile range: 10%–22.5%) were older, more likely to have atrial fibrillation, and had higher jugular venous pressure (P < .05 for all). At baseline, higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and troponin I were independently associated with lower LA reservoir and contractile strain (P_adjusted < .05 for all comparisons). Higher LA reservoir strain (β coefficient per 1-unit increase: −21.2, 95% CI: −38.8, −3.7; P = .02) was independently associated with reduction in NT-proBNP at 24 weeks. Conclusion: In HFpEF, LA myopathy is characterized by elevation in biomarkers of neurohormonal activation and myocardial necrosis. Lower LA function is associated with continued elevation in NT-proBNP over time, suggesting that LA myopathy is associated with persistent congestion in HFpEF.

Original language	English (US)
Pages (from-to)	270-275
Number of pages	6
Journal	Journal of Cardiac Failure
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.cardfail.2019.12.001
State	Published - Mar 2020

Funding

Funding: This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number U10 HL084904 and award numbers U10 HL110297 , U10 HL110342 , U10 HL110309 , U10 HL110262 , U10 HL110338 , U10 HL110312 , U10 HL110302 , U10 HL110336 , U10 HL110337 , and T32HL069771 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding: This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number U10 HL084904 and award numbers U10 HL110297, U10 HL110342, U10 HL110309, U10 HL110262, U10 HL110338, U10 HL110312, U10 HL110302, U10 HL110336, U10 HL110337, and T32HL069771. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.R.B.P. is supported by the NHLBI T32 postdoctoral training grant (T32HL069771). M.V. is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa, and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. J.B. received research support from the NIH and European Union; and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. E.J.V. received research grants from the NHLBI, Novartis, Amgen, Actelion, and Pfizer; and has been a consultant to Novartis and Philips. S.J.S. received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, and United Therapeutics; he is supported by NIH R01 HL107577, R01 HL127028, and R01 HL140731, and American Heart Association grants 16SFRN28780016 and 15CVGPSD27260148. All other authors have reported that they have no other relationships relevant to the contents of this paper to disclose.

Keywords

Heart failure with preserved ejection fraction
biomarker
function
left atrium
strain

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.cardfail.2019.12.001

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Patel, R. B., Alenezi, F., Sun, J. L., Alhanti, B., Vaduganathan, M., Oh, J. K., Redfield, M. M., Butler, J., Hernandez, A. F., Velazquez, E. J., & Shah, S. J. (2020). Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy. Journal of Cardiac Failure, 26(3), 270-275. https://doi.org/10.1016/j.cardfail.2019.12.001

@article{7f8d6453d2b94fc8a7829441facc3ae6,

title = "Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy",

abstract = "Background: Although left atrial (LA) mechanical dysfunction in heart failure with preserved ejection fraction (HFpEF) is associated with poor clinical outcomes, the influence of LA myopathy on temporal changes in cardiovascular biomarkers is unclear. Methods and Results: We evaluated biomarker correlates of LA myopathy, as defined by reduced LA strain, and the associations of LA strain with longitudinal changes in biomarkers among participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. LA speckle-tracking was performed on baseline echocardiograms of RELAX participants to measure LA reservoir and LA contractile strain. Of the 216 RELAX participants, 169 (78%) had measurable LA strain and biomarker data. Participants with LA reservoir strain below median (13.5%, interquartile range: 10%–22.5%) were older, more likely to have atrial fibrillation, and had higher jugular venous pressure (P < .05 for all). At baseline, higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and troponin I were independently associated with lower LA reservoir and contractile strain (Padjusted < .05 for all comparisons). Higher LA reservoir strain (β coefficient per 1-unit increase: −21.2, 95% CI: −38.8, −3.7; P = .02) was independently associated with reduction in NT-proBNP at 24 weeks. Conclusion: In HFpEF, LA myopathy is characterized by elevation in biomarkers of neurohormonal activation and myocardial necrosis. Lower LA function is associated with continued elevation in NT-proBNP over time, suggesting that LA myopathy is associated with persistent congestion in HFpEF.",

keywords = "Heart failure with preserved ejection fraction, biomarker, function, left atrium, strain",

author = "Patel, {Ravi B.} and Fawaz Alenezi and Sun, {Jie Lena} and Brooke Alhanti and Muthiah Vaduganathan and Oh, {Jae K.} and Redfield, {Margaret M.} and Javed Butler and Hernandez, {Adrian F.} and Velazquez, {Eric J.} and Shah, {Sanjiv J.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = mar,

doi = "10.1016/j.cardfail.2019.12.001",

language = "English (US)",

volume = "26",

pages = "270--275",

journal = "Journal of Cardiac Failure",

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Patel, RB, Alenezi, F, Sun, JL, Alhanti, B, Vaduganathan, M, Oh, JK, Redfield, MM, Butler, J, Hernandez, AF, Velazquez, EJ & Shah, SJ 2020, 'Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy', Journal of Cardiac Failure, vol. 26, no. 3, pp. 270-275. https://doi.org/10.1016/j.cardfail.2019.12.001

TY - JOUR

T1 - Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction

T2 - Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy

AU - Patel, Ravi B.

AU - Alenezi, Fawaz

AU - Sun, Jie Lena

AU - Alhanti, Brooke

AU - Vaduganathan, Muthiah

AU - Oh, Jae K.

AU - Redfield, Margaret M.

AU - Butler, Javed

AU - Hernandez, Adrian F.

AU - Velazquez, Eric J.

AU - Shah, Sanjiv J.

PY - 2020/3

Y1 - 2020/3

N2 - Background: Although left atrial (LA) mechanical dysfunction in heart failure with preserved ejection fraction (HFpEF) is associated with poor clinical outcomes, the influence of LA myopathy on temporal changes in cardiovascular biomarkers is unclear. Methods and Results: We evaluated biomarker correlates of LA myopathy, as defined by reduced LA strain, and the associations of LA strain with longitudinal changes in biomarkers among participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. LA speckle-tracking was performed on baseline echocardiograms of RELAX participants to measure LA reservoir and LA contractile strain. Of the 216 RELAX participants, 169 (78%) had measurable LA strain and biomarker data. Participants with LA reservoir strain below median (13.5%, interquartile range: 10%–22.5%) were older, more likely to have atrial fibrillation, and had higher jugular venous pressure (P < .05 for all). At baseline, higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and troponin I were independently associated with lower LA reservoir and contractile strain (Padjusted < .05 for all comparisons). Higher LA reservoir strain (β coefficient per 1-unit increase: −21.2, 95% CI: −38.8, −3.7; P = .02) was independently associated with reduction in NT-proBNP at 24 weeks. Conclusion: In HFpEF, LA myopathy is characterized by elevation in biomarkers of neurohormonal activation and myocardial necrosis. Lower LA function is associated with continued elevation in NT-proBNP over time, suggesting that LA myopathy is associated with persistent congestion in HFpEF.

AB - Background: Although left atrial (LA) mechanical dysfunction in heart failure with preserved ejection fraction (HFpEF) is associated with poor clinical outcomes, the influence of LA myopathy on temporal changes in cardiovascular biomarkers is unclear. Methods and Results: We evaluated biomarker correlates of LA myopathy, as defined by reduced LA strain, and the associations of LA strain with longitudinal changes in biomarkers among participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. LA speckle-tracking was performed on baseline echocardiograms of RELAX participants to measure LA reservoir and LA contractile strain. Of the 216 RELAX participants, 169 (78%) had measurable LA strain and biomarker data. Participants with LA reservoir strain below median (13.5%, interquartile range: 10%–22.5%) were older, more likely to have atrial fibrillation, and had higher jugular venous pressure (P < .05 for all). At baseline, higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and troponin I were independently associated with lower LA reservoir and contractile strain (Padjusted < .05 for all comparisons). Higher LA reservoir strain (β coefficient per 1-unit increase: −21.2, 95% CI: −38.8, −3.7; P = .02) was independently associated with reduction in NT-proBNP at 24 weeks. Conclusion: In HFpEF, LA myopathy is characterized by elevation in biomarkers of neurohormonal activation and myocardial necrosis. Lower LA function is associated with continued elevation in NT-proBNP over time, suggesting that LA myopathy is associated with persistent congestion in HFpEF.

KW - Heart failure with preserved ejection fraction

KW - biomarker

KW - function

KW - left atrium

KW - strain

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Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Biomarkers in Left Atrial Myopathy

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