Effects of Sacubitril/Valsartan on biomarkers of fibrosis and inflammation in patients with heart failure with reduced ejection fraction

BMC Cardiovasc Disord. 2022 May 13;22(1):217. doi: 10.1186/s12872-022-02647-0.

Abstract

Aims: To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V).

Methods and results: A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05).

Conclusions: A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.

Keywords: Biomarkers; Fibrosis; Heart failure; Left ventricular ejection fraction; Sacubitril/Valsartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobutyrates
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biomarkers
  • Biphenyl Compounds / therapeutic use
  • Chitinase-3-Like Protein 1
  • Fibrosis
  • Heart Failure* / complications
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Humans
  • Inflammation / complications
  • Stroke Volume
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use
  • Valsartan / therapeutic use
  • Ventricular Dysfunction, Left* / complications
  • Ventricular Function, Left

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biomarkers
  • Biphenyl Compounds
  • Chitinase-3-Like Protein 1
  • Tetrazoles
  • sacubitril
  • Valsartan