ABSTRACT
The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow-mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function.
Subject(s)
Heart Failure , Neprilysin , Aminobutyrates/pharmacology , Angiotensins/pharmacology , Female , Heart Failure/drug therapy , Humans , Male , Pilot Projects , Pulse Wave Analysis , Receptors, Angiotensin , Stroke Volume/physiology , Ventricular Function, LeftABSTRACT
Aortic stenosis (AS) is the most common valvular heart disease in the world. It is a disease of the elderly and as our population is getting older in both the developed and the developing world, there has been an increase in the prevalence of AS. It is impacting the mortality and morbidity of our elderly population. It is also causing a huge burden on the healthcare system. There has been tremendous progress in our understanding of AS in recent years. Lately, studies have shown that AS is not just a disease of the aortic valve but it affects the entire systemic vasculature. There are studies looking at more sophisticated measures of disease severity that might better predict the optimal timing of valve replacement. The improvement in our understanding in etiology and pathophysiology of the disease process has led to a number of trials with possible treatment options for AS. In this review, we talk about our understanding of the disease and latest developments in disease assessment and management. We look forward to a time when there will be medical treatment for AS.
