Sacubitril/valsartan in an experimental model of heart failure with preserved ejection fraction

• Published in: Cardiovascular research Vol. 118; no. Supplement_1
• Main Authors: De Angelis, A, Cappetta, D, Telesca, M, Bellocchio, G, Urbanek, K, Berrino, L
• Format: Journal Article
• Language: English
• Published: Oxford University Press 10.06.2022
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvac066.104

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministry for Education, University and Research Introduction The majority of elderly patients with heart failure has a preserved ejection fraction (HFpEF) that constitutes a syndrome characterized by frequent hospitalizations and high mortality. Despite the growing social burden of HFpEF, the comprehension of its pathophysiology is incomplete, and treatment remains largely undefined. Aging itself may contribute independently to deterioration of diastolic function. Methods 18-month old female Fischer 344 rats were treated with oral administration of either sacubitril/valsartan (60 mg/kg/die, 1:1 ratio) or valsartan alone (30 mg/kg/die) for 12 weeks. Tail-cuff method was used to monitor blood pressure weekly. Echocardiography and left ventricle catheterization were employed to assess systolic and diastolic function, at baseline, and before sacrifice. Cardiac tissue was used for molecular biology and histochemistry assays. Results Tail-cuff analysis indicated a comparable decrease in blood pressure between treatments. Hypertrophy also showed a significant reduction with both treatments. On the contrary, myocardial function analysis demonstrated that no treatment was efficacy on diastolic dysfunction. The lack of improvement of cardiac function could be attributed to the inability of the treatments to counteract the accumulation of fibrotic tissue in the left ventricle, which, in turn, is attributable to the failure to reduce the inflammatory process and oxidative stress, and to the inability to modulate angiotensin II pathway. Conclusion Our results evidenced that both sacubitril/valsartan or valsartan treatment was able to improve diastolic function and pro-fibrotic remodeling, partly due to a lack of effect on classical and non-classical pathways of angiotensin II.