Association Between Angiotensin Receptor–Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction. (15th May 2021)

• Record Type: Journal Article
• Authors: Murphy, Sean P.; Prescott, Margaret F.; Maisel, Alan S.; Butler, Javed; Piña, Ileana L.; Felker, G. Michael; Ward, Jonathan H.; Williamson, Kristin M.; Camacho, Alexander; Kandanelly, Ritvik R.; Solomon, Scott D.; Januzzi, James L.
• Is Part Of: Circulation. Volume 14:Number 6(2021)
• Page Start: e008410
• Publication Date: 2021-05-15
• Subjects: biomarkers -- echocardiography -- heart failure -- prospective studies -- valsartan; Heart failure -- Periodicals; 616.129005
• DOI: 10.1161/CIRCHEARTFAILURE.120.008410
• Languages: English
• ISSNs: 1941-3289

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : 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/m 2, 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.