Improved vascular function and functional capacity following l-citrulline administration in patients with heart failure with preserved ejection fraction: a single-arm, open-label, prospective pilot study

There is accumulating evidence for both peripheral vascular dysfunction and impaired functional capacity in patients with heart failure with a preserved ejection fraction (HFpEF). Although derangements in the l-arginine-nitric oxide (l-Arg-NO) pathway are likely to contribute to these aspects of HFpEF pathophysiology, the impact of increased NO substrate on vascular health and physical capacity has not been evaluated in this patient population. Thus, using a single-arm study design, we evaluated the impact of enteral l-citrulline (l-Cit, 6 g/day for 7 days), a precursor for l-Arg biosynthesis, on vascular function [flow-mediated dilation (FMD), reactive hyperemia (RH), and passive limb movement (PLM)], functional capacity [6-min walk test (6MWT)], and biomarkers of l-Arg-NO signaling in 14 patients with HFpEF (