Abstract 12306: Changes of Metabolomic Profiling Are Associated With Reduced Exercise Capacity in Patients With Heart Failure

Abstract

Background: Exercise intolerance is a major clinical manifestation, and closely related to poor prognosis in heart failure (HF) patients. Metabolic derangements have been shown to play an important role in this phenomenon. Recent metabolomic investigations have highlighted several novel biochemical pathways in HF, however, metabolic profiling associated with exercise capacity has not been elucidated. We thus investigated the metabolites associated with exercise capacity by using global metabolomic analysis of plasma samples in HF patients. Methods: Ten consecutive HF patients with reduced ejection fraction (57 ± 12 years old, New York Heart Association class II - III) and 5 age-matched healthy subjects as controls (56 ± 3 years old) were studied. Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO 2 ) and VE/VCO 2 slope were measured by cardiopulmonary exercise test. Results: A total of 233 charged metabolites were identified and quantified absolutely using standard chemicals for each metabolite. Significant increases in arginine methylation, phospholipid metabolites, and urea cycle metabolites were observed in HF patients compared to controls (Figure). Peak VO 2 was negatively correlated with methylarginine including asymmetric dimethylarginine (ADMA) (r=-0.77, P<0.001) and symmetric dimethylarginine (SDMA) (r=-0.65, P=0.040) levels, and phospholipid metabolites including choline (r=-0.63, P=0.049) and N,N -dimethylglycine (r=-0.75, P=0.011) levels in HF patients. VE/VCO 2 slope was positively correlated with N,N -dimethylglycine (r=0.72, P=0.026) and Urea (r=0.82, P=0.006) levels. Conclusions: Increases in metabolites of arginine methylation, phospholipid metabolism, and urea cycle were associated with exercise intolerance in HF. These results provide mechanistic insights into exercise intolerance associated with HF.