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Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

Publication ,  Journal Article
Murphy, SP; Prescott, MF; Maisel, AS; Butler, J; Piña, IL; Felker, GM; Ward, JH; Williamson, KM; Camacho, A; Kandanelly, RR; Solomon, SD; Januzzi, JL
Published in: Circ Heart Fail
June 2021

BACKGROUND: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. METHODS: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. RESULTS: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures. CONCLUSIONS: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

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Published In

Circ Heart Fail

DOI

EISSN

1941-3297

Publication Date

June 2021

Volume

14

Issue

6

Start / End Page

e008410

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Valsartan
  • Stroke Volume
  • Receptors, Angiotensin
  • Neprilysin
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
 

Citation

APA
Chicago
ICMJE
MLA
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Murphy, S. P., Prescott, M. F., Maisel, A. S., Butler, J., Piña, I. L., Felker, G. M., … Januzzi, J. L. (2021). Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction. Circ Heart Fail, 14(6), e008410. https://doi.org/10.1161/CIRCHEARTFAILURE.120.008410
Murphy, Sean P., Margaret F. Prescott, Alan S. Maisel, Javed Butler, Ileana L. Piña, G Michael Felker, Jonathan H. Ward, et al. “Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.Circ Heart Fail 14, no. 6 (June 2021): e008410. https://doi.org/10.1161/CIRCHEARTFAILURE.120.008410.
Murphy SP, Prescott MF, Maisel AS, Butler J, Piña IL, Felker GM, et al. Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction. Circ Heart Fail. 2021 Jun;14(6):e008410.
Murphy, Sean P., et al. “Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.Circ Heart Fail, vol. 14, no. 6, June 2021, p. e008410. Pubmed, doi:10.1161/CIRCHEARTFAILURE.120.008410.
Murphy SP, Prescott MF, Maisel AS, Butler J, Piña IL, Felker GM, Ward JH, Williamson KM, Camacho A, Kandanelly RR, Solomon SD, Januzzi JL. Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction. Circ Heart Fail. 2021 Jun;14(6):e008410.

Published In

Circ Heart Fail

DOI

EISSN

1941-3297

Publication Date

June 2021

Volume

14

Issue

6

Start / End Page

e008410

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Valsartan
  • Stroke Volume
  • Receptors, Angiotensin
  • Neprilysin
  • Middle Aged
  • Male
  • Humans
  • Heart Failure