Heart Failure Duration and Mechanistic Efficacy of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction

Background: Although sacubitril/valsartan (Sac/Val) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF), gaps in care continue to exist for those with newer onset HFrEF vs those with longer durations of disease.Methods and Results: We categorized 794 persons with HFrEF (EF of <40%) according to a HF duration of less than 12 months, 12-24 months, 24-60 months, and more than> 60 months. After the initiation of Sac/Val, concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were measured, and Kansas City Cardiomy-opathy Questionnaire 23 scores were obtained serially from baseline to 12 months. The left ventricular ejection fraction was measured by echocardiography. Significant decreases in the concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were observed regardless of HF duration (P < .001). Comparable gains in Kansas City Cardiomyopathy Questionnaire 23 scores were achieved in all HF duration catego-ries. Moreover, consistent reverse cardiac remodeling in all HF duration categories occurred, with the absolute left ventricular ejection fraction improvement by 12 months across HF duration groups of 12.2%, 6.9%, 8.5%, and 8.6% for HF duration of less than 12 months, 12-24 months, 24-60 months, and more than 60 months, respectively.Conclusions: The initiation of Sac/Val decreases prognostic biomarkers, improves health sta-tus, and reverses cardiac remodeling processes, regardless of HF duration.Brief lay summary: We categorized 794 persons with heart failure owing to a low ejection fraction according to disease duration into 4 groups: less than 12 months, 12-24 months, 24-60 months, and more than 60 months. After the initiation of sacubitril/valsartan (Entresto), we found that regardless of the duration of heart failure significant improvements occurred in cardiac biomarkers, patients felt better with improved health status and on test-ing with cardiac ultrasound examination, improvement in heart size, and function occurred. These results suggest that, regardless of heart failure duration, patients with a reduced ejec-tion fraction would benefit from use of sacubitril/valsartan for their care. (J Cardiac Fail 2022;28:1673-1682)