Journal
EUROPEAN HEART JOURNAL
Volume 29, Issue 20, Pages 2506-2513Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehn360
Keywords
Heart failure; Arginine; Methylation; Diastolic function; Prognosis
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Funding
- American Society of Echocardiography
- GlaxoSmithKline Pharmaceuticals
- Roche Diagnostics Inc
- National Institutes of Health [P01 HL076491, P01 HL77107, P01 HL087018]
- National Center for Research Resources
- CTSA, Cleveland, Ohio [1UL1RR024989]
- American Heart Association Ohio Valley Affiliates [0465266B]
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Aims To investigate the association of arginine methylation with myocardial function and prognosis in chronic systolic heart failure patients. Methods and results Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as N-mono-methylarginine (MMA) and methyl-lysine, were simultaneously measured by tandem mass spectrometry in 132 patients with chronic systolic heart failure with echocardiographic evaluation and follow-up. Increasing ADMA and SDMA levels were associated with elevated natriuretic peptide levels (both P < 0.001), and increasing SDMA levels were associated with worsening renal function (P < 0.001). Higher plasma levels of methylated arginine metabolites (but not methyl-lysine) were associated with the presence of left ventricular (LV) diastolic dysfunction (E/septal E', Spearman's r = 0.31-0.36, P < 0.001). Patients taking beta-blockers had lower ADMA levels than those not taking beta-blockers [0.42 (0.33, 0.50) vs. 0.51 (0.40, 0.58), P < 0.001]. Only increasing ADMA levels were associated with advanced right ventricular (RV) systolic dysfunction. Elevated ADMA levels remained a consistent independent predictor of adverse clinical events (hazard ratio = 1.64, 95% CI: 1.20-2.22, P = 0.002). Conclusion In chronic systolic heart failure, accumulation of methylated arginine metabolites is associated with the presence of LV diastolic dysfunction. Among the methylated derivatives of arginine, ADMA provides the strongest independent prediction of disease progression and adverse long-term outcomes.
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