Effects of Angiotensin Receptor Neprilysin Inhibition on Vascular Function, Central Pressures and Aortic Wave Reflection Parameters in Heart Failure
Authors: Nathaniel Sangeetha D. , McGinty Shane , Welti Laura M. , Edwards David G. , Farquhar William B. , Witman Melissa A.H. , Hosmane Vinay , Wenner Megan M. 
Published: April 2020

Angiotensin Receptor Neprilysin inhibitors (ARNi) are a new therapy for heart failure patients with reduced ejection fraction (HFrEF), which improves vasodilation and diuresis. ARNi is superior to conventional treatment in reducing mortality in HFrEF; this benefit is likely beyond the reduction in both fluid retention and blood pressure (BP). The mechanism(s) for reduced mortality noted with ARNi in HFrEF are unclear but may be related to improved vascular function.PURPOSEWe hypothesized that endothelial function, arterial stiffness, central BP and central wave reflection would improve after 12 weeks of ARNi in HFrEF.METHODSHFrEF participants with New York Heart Association (NYHA) class II‐III were recruited from local cardiology clinics and completed a baseline experimental visit and follow up visit 12 weeks later: 7 patients were prescribed ARNi by their cardiologist [61±11 years, Men: 5, BMI: 31±7 kg/m2, EF: 28±6%; 5 with Non‐ischemic cardiomyopathy (NICM)], and 8 participants continued on conventional treatment [CON: 58±6 years, Men: 5, BMI: 30±5 kg/m2, EF: 30±5% and NICM: 5; all P=NS]. During each experimental visit, endothelial function was assessed by brachial artery flow‐mediated dilation (FMD) using standard techniques. Arterial stiffness was assessed via pulse wave velocity (PWV) (Sphygmocore PVx system). Central aortic BP and surrogate markers of central aortic wave reflection [augmentation index (AIx)] were assessed using radial applanation tonometry; central aortic BP was derived using a generalized transfer function. Statistical comparisons were performed using 2×2 repeated‐measures ANOVA.RESULTSResting mean arterial BP (MAP) was similar between ARNi (94±16 mmHg) and CON (85±10 mmHg; P=0.22); MAP reduced after 12 weeks of ARNi (80±8 mmHg; P=0.01) and was unchanged in CON (89±17 mmHg). At baseline, FMD was similar between ARNi (2.8±3.3%) and CON (5.2±3.6%; P=0.20); however, FMD tended to improve after 12 weeks of ARNi (5.1±1.5%; P=0.07) and remained unchanged in CON (5.4±3.9%). PWV was similar at baseline between ARNi (7.8±2.5 m/s) and CON (7.1±2.8 m/s; P=0.61); PWV reduced after 12 weeks of ARNi (6.5±1.7 m/s; P=0.02) and was unchanged in CON (7.7±2.6 m/s). When PWV was adjusted to MAP, PWV tended to reduce after 12 weeks of ARNi (P=0.07). Aortic systolic BP was similar between ARNi (122±22 mmHg) and CON (108±15 mmHg; P=0.17); aortic systolic BP decreased after 12 weeks of ARNi (106±15 mmHg; P=0.02) but was unchanged in CON (114±26 mmHg). AIx was similar between ARNi (29±15%) and CON (28±14%); and was unchanged after 12 weeks of ARNi (26±8%) and remained unchanged in CON (31±14%; P=NS).CONCLUSIONThese preliminary data suggest that 12 weeks of ARNi therapy reduces blood pressure (peripheral and central) in HFrEF patients. Furthermore, ARNi therapy may improve endothelial function and arterial stiffness. Additional data are needed to fully understand the impact of ARNi on vascular function, aortic BP and aortic wave reflection in HFrEF.Support or Funding InformationACSM grant 19‐00934 and P20 GM 113125