Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload

• Main Authors: Einar Sjaastad Nordén, Bård Andre Bendiksen, Henriette Andresen, Kaja Knudsen Bergo, Emil Knut Espe, Almira Hasic, Ida Marie Hauge‐Iversen, Ioanni Veras, Rizwan I. Hussain, Ivar Sjaastad, Geir Christensen, Alessandro Cataliotti
• Format: Article
• Language: English
• Published: Wiley 2021-04-01
• Series: ESC Heart Failure
• Subjects: Cardiac pressure overload; Sacubitril/valsartan; Heart failure; Therapy; Hypertrophy; Diastolic dysfunction
• Online Access: https://doi.org/10.1002/ehf2.13177

Abstract Aims Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin–angiotensin–aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with preserved ejection fraction (HFpEF). Methods and results Sprague–Dawley rats underwent aortic banding or sham (n = 16) surgery and were randomized to sac/val (n = 28), valsartan (n = 29), or vehicle (n = 26) treatment for 8 weeks. Sac/val reduced left ventricular weight by 11% compared with vehicle (P = 0.01) and 9% compared with valsartan alone (P = 0.04). Only valsartan reduced blood pressure compared with sham (P = 0.02). Longitudinal early diastolic strain rate was preserved in sac/val compared with sham, while it was reduced by 23% in vehicle (P = 0.03) and 24% in valsartan (P = 0.02). Diastolic dysfunction, measured by E/e'SR, increased by 68% in vehicle (P < 0.01) and 80% in valsartan alone (P < 0.001), while sac/val showed no increase. Neither sac/val nor valsartan prevented interstitial fibrosis. Although ejection fraction was preserved, we observed mild systolic dysfunction, with vehicle showing a 28% decrease in longitudinal strain (P < 0.01). Neither sac/val nor valsartan treatment improved this dysfunction. Conclusions In a model of HFpEF induced by cardiac pressure overload, sac/val reduced hypertrophy compared with valsartan alone and ameliorated diastolic dysfunction. These effects were independent of blood pressure. Early systolic dysfunction was not affected, supporting the notion that sac/val has the largest potential in conditions characterized by reduced ejection fraction. Observed anti‐hypertrophic effects in preserved ejection fraction implicate potential benefit of sac/val in the clinical setting of hypertrophic remodelling and impaired diastolic function.