Echocardiographic evaluation of the effects of sacubitril-valsartan on vascular properties in heart failure patients

Int J Cardiovasc Imaging. 2020 Feb;36(2):271-278. doi: 10.1007/s10554-019-01708-4. Epub 2019 Oct 3.

Abstract

Increased vascular stiffness is known to be an independent predictor of mortality in patients with heart failure with reduced ejection fraction (HFrEF). The effects of sacubitril-valsartan on vascular structure and function have not been systematically studied in this patient population. We hypothesized that aortic distensibility (AD) and fractional area change (AFAC), as assessed by 2D transthoracic echocardiography (TTE), would improve over time in HFrEF patients on sacubitril-valsartan therapy, due to the vasodilatory properties of the medication. We prospectively studied 30 patients with HFrEF (25 < EF < 40%) on optimal guideline-directed medical therapy who were subsequently started on sacubitril-valsartan. Patients underwent serial 2D TTE imaging at baseline, 3 and 6 months following therapy initiation. Ascending aortic diameters were measured 3 cm above the aortic valve in the parasternal long-axis view and used to calculate AD and AFAC, two markers of vascular compliance. For reference, we also measured AD and AFAC in 30 healthy, age and gender-matched controls at a single time point. Normal controls had significantly higher values of AD and AFAC than HFrEF patients at baseline (AD: 4.0 ± 1.1 vs. 2.2 ± 0.9 cm2dyne-110-3, p < 0.0001 and AFAC: 18.8 ± 3.7% vs. 10.3 ± 4.3%, p < 0.0001). In HFrEF patients on sacubitril-valsartan, both indices of aortic compliance progressively improved towards normal from baseline to 6 months: AD from 2.2 ± 0.9 to 3.6 ± 1.5 cm2dyne-110-3 (p < 0.0001) and AFAC from 10.3 ± 4.3 to 13.7 ± 4.1% (p < 0.0001). In conclusion, AD and AFAC are decreased in patients with HFrEF and gradually improve with sacubitril-valsartan treatment. The echocardiographic markers used in this study may become a useful tool to assess the effectiveness of sacubitril-valsartan therapy in HFrEF patients.

Keywords: Aorta; Aortic distensibility; Entresto; Vascular stiffness.

MeSH terms

  • Adult
  • Aged
  • Aminobutyrates / adverse effects
  • Aminobutyrates / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Biphenyl Compounds
  • Case-Control Studies
  • Drug Combinations
  • Echocardiography*
  • Female
  • Heart Failure / diagnostic imaging*
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Neprilysin / antagonists & inhibitors
  • Predictive Value of Tests
  • Prospective Studies
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Tetrazoles / adverse effects
  • Tetrazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Valsartan
  • Vascular Stiffness / drug effects*
  • Vasodilation / drug effects*

Substances

  • Aminobutyrates
  • Angiotensin II Type 1 Receptor Blockers
  • Biphenyl Compounds
  • Drug Combinations
  • Protease Inhibitors
  • Tetrazoles
  • Valsartan
  • Neprilysin
  • sacubitril and valsartan sodium hydrate drug combination