Abstract 3763: Diminished Global Arginine Bioavailability Predicts Adverse Prognosis in Patients with Chronic Systolic Heart Failure
Background: Diminished bioavailability of arginine, the precursor for nitric oxide production, is associated with endothelial dysfunction. Catabolic pathways for depleting arginine include arginase and nitric oxide synthase, resulting in elevated products of ornithine and citrulline, respectively. An estimate global arginine bioavailability ratio (GABR) can be defined as [arginine/(ornithine + citrulline)]. The prognostic significance of GABR in patients with heart failure is unknown.
Methods: We performed comprehensive transthoracic echocardiographic analysis and measured the levels of plasma arginine metabolites using liquid chromatography-tandem mass spectrometry (LC/MS/MS) in 138 stable symptomatic heart failure patients with left ventricular ejection fraction (LVEF) ≤35%. Metabolites analyzed include arginine, ornithine, and citrulline. Clinical outcomes (death, transplant, heart failure hospitalization) were followed for 25 months.
Results: In univariable analyses, lower GABR was related to increasing age (r=−0.19, p=0.04), higher NYHA class (r =−0.19, p=0.04), higher plasma NT-proBNP (r=−0.48, p<0.001), more advanced diastolic and renal dysfunction, as well as more severe right ventricular dysfunction (all <0.001). Patients taking beta-blockers have significantly higher GABR (0.93 ± 0.4 vs 0.70 ±0.3, p<0.001). Lower GABR was associated with more long-term clinical events (see Figure⇓).
Conclusion: Heart failure is characterized by an arginine-deficient state, and diminishing arginine availability is associated with increasing severity of systolic and diastolic heart failure, as well as poorer long-term outcomes.