LAUSR

There is accumulating evidence for both peripheral vascular dysfunction and impaired functional capacity in patients with heart failure with a preserved ejection fraction (HFpEF). While 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, 6g/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 (six-minute walk test [6MWT]) and biomarkers of L-Arg-NO signalling in 14 patients with HFpEF (n = 14, 4M/10F, 70±10yrs, EF: 66±7%). Compared to baseline (0d), 7 days of L-Cit administration improved FMD (0d: 2.5±0.5%, 7d: 4.7±0.9%), RH (0d: 450±46ml, 7d: 574±62ml), PLM area-under-the-curve (0d: 139±36ml, 7d: 198±32ml), and 6MWT distance (0d: 377±27m, 7d: 397±27m) (p<0.05). An increase in plasma L-Cit (0d: 42 ± 3µM/L, 7d: 370 ± 60 µM/L), L-Arg (0d: 65 ± 8µM/L, 7d: 257 ± 25µM/L), and the ratio of L-Arg to asymmetric dimethylarginine (ADMA) (0d: 136±14AU, 7d: 481±50AU) (p<0.05) was also observed. Though preliminary in nature, these functional and biomarker assessments demonstrate a potential benefit of L-Cit administration in patients with HFpEF, findings that provide new insight into the mechanisms that govern vascular and physical dysfunction in this patient group.