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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Cardiac Failure
DOIs
StateAccepted/In press - Jan 1 2020

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Muscular Diseases
Heart Failure
Biomarkers
Natriuretic Peptides
Left Atrial Function
Type 5 Cyclic Nucleotide Phosphodiesterases
Troponin I
Venous Pressure
Endothelin-1
Atrial Fibrillation
Necrosis
Neck

Keywords

  • biomarker
  • function
  • Heart failure with preserved ejection fraction
  • left atrium
  • strain

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction : Insights From the RELAX Trial. / Patel, Ravi B.; Alenezi, Fawaz; Sun, Jie Lena; Alhanti, Brooke; Vaduganathan, Muthiah; Oh, Jae K.; Redfield, Margaret M.; Butler, Javed; Hernandez, Adrian F.; Velazquez, Eric J.; Shah, Sanjiv J.

In: Journal of Cardiac Failure, 01.01.2020.

Research output: Contribution to journalArticle

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', Journal of Cardiac Failure. https://doi.org/10.1016/j.cardfail.2019.12.001
Patel, Ravi B. ; Alenezi, Fawaz ; Sun, Jie Lena ; Alhanti, Brooke ; Vaduganathan, Muthiah ; Oh, Jae K. ; Redfield, Margaret M. ; Butler, Javed ; Hernandez, Adrian F. ; Velazquez, Eric J. ; Shah, Sanjiv J. / Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction : Insights From the RELAX Trial. In: Journal of Cardiac Failure. 2020.
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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.",
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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.

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Y1 - 2020/1/1

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.

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