title: Diminished global arginine bioavailability as a metabolic defect in chronic systolic heart failure.
abstract: BACKGROUND
  Systemic alterations in arginine bioavailability occur in heart failure (HF) patients with more advanced myocardial dysfunction and poorer clinical outcomes, and they improve with beta-blocker therapy.
  
  
  RESULTS
  We measured fasting plasma levels of L-arginine and related biogenic amine metabolites in 138 stable symptomatic HF patients with left ventricular ejection fraction ≤35% and comprehensive echocardiographic evaluation. Long-term adverse clinical outcomes (death and cardiac transplantation) were followed for 5 years. Lower global arginine bioavailability ratio (GABR; ratio of L-arginine to L-ornithine + L-citrulline) was associated with higher plasma natriuretic peptide levels, more advanced left ventricular diastolic dysfunction, and more severe right ventricular systolic dysfunction (all P < .001). Patients taking beta-blockers had significantly higher GABR than those not taking beta-blockers (0.86 [interquartile range (IQR) 0.68-1.17] vs 0.61 [0.44-0.89]; P < .001). Subjects with higher GABR experienced fewer long-term adverse clinical events (hazard ratio 0.61 [95% confidence interval 0.43-0.84]; P = .002). In an independent beta-blocker naïve patient cohort, GABR increased following long-term (6 month) beta-blocker therapy (0.89 [IQR 0.52-1.07] to 0.97 [0.81-1.20]; P = .019).
  
  
  CONCLUSIONS
  In patients with chronic systolic heart failure, diminished global L-arginine bioavailability is associated with more advanced myocardial dysfunction and poorer long-term adverse clinical outcomes. GABR levels improved with beta-blocker therapy.
authors: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. tangw@ccf.org
authors: W H Wilson
authors: WH
authors: Tang
authors: Kevin
authors: K
authors: Shrestha
authors: Zeneng
authors: Z
authors: Wang
authors: Richard W
authors: RW
authors: Troughton
authors: Allan L
authors: AL
authors: Klein
authors: Stanley L
authors: SL
authors: Hazen
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000097:blood*; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001120:Arginine
references: Atherosclerosis. 2011 Sep;218(1):220-5
references: 21632053
references: Clin Exp Pharmacol Physiol. 2008 Apr;35(4):483-8
references: 18307746
references: Circ Res. 2002 Dec 13;91(12):1198-203
references: 12480822
references: J Am Coll Cardiol. 2009 Jun 2;53(22):2061-7
references: 19477356
references: J Am Coll Cardiol. 2012 Mar 27;59(13):1150-8
references: 22440215
references: Am J Cardiol. 2005 Jul 15;96(2):257-62
references: 16018853
references: J Am Coll Cardiol. 2007 May 15;49(19):1903-14
references: 17498573
references: J Clin Endocrinol Metab. 1993 Apr;76(4):832-8
references: 8473392
references: Int J Cardiol. 2008 Apr 10;125(2):273-6
references: 18053592
references: J Am Coll Cardiol. 2007 Jun 19;49(24):2364-70
references: 17572253
references: Am J Cardiol. 2008 Feb 1;101(3):370-3
references: 18237602
references: Circulation. 1998 Jul 14;98(2):132-9
references: 9679719
references: Am J Respir Crit Care Med. 2010 Sep 1;182(5):652-60
references: 20508210
references: Heart Vessels. 2003 Sep;18(4):177-82
references: 14520484
references: Diabet Med. 2012 Oct;29(10):e365-8
references: 22803961
references: J Am Coll Cardiol. 2004 Feb 4;43(3):416-22
references: 15013124
references: J Am Soc Echocardiogr. 2010 Jul;23(7):685-713; quiz 786-8
references: 20620859
references: J Clin Endocrinol Metab. 1986 Jul;63(1):72-9
references: 2940257
references: Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4759-64
references: 16537391
references: Am J Cardiol. 2001 Oct 15;88(8):867-70
references: 11676949
references: Circulation. 1996 Mar 15;93(6):1087-94
references: 8653828
references: JAMA. 2005 Jul 6;294(1):81-90
references: 15998894
references: Nitric Oxide. 1997 Oct;1(5):386-96
references: 9441909
references: J Mol Med (Berl). 2010 Oct;88(10):1011-20
references: 20820751
references: Cardiovasc Res. 2007 Sep 1;75(4):770-81
references: 17582388
references: J Card Fail. 2004 Jun;10(3):244-9
references: 15190535