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Both are synthesized via L-arginine:glycine amidinotransferase (AGAT), such that AGAT\u2212\/\u2212 mice have a combined creatine and homoarginine deficiency. We hypothesized that this would be detrimental in the setting of chronic heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Study 1: homoarginine deficiency\u2014female AGAT\u2212\/\u2212 and wild-type mice were given creatine-supplemented diet so that both had normal myocardial creatine levels, but only AGAT\u2212\/\u2212 had low plasma homoarginine. Myocardial infarction (MI) was surgically induced and left ventricular (LV) structure and function assessed at 6\u20137 weeks by in vivo imaging and haemodynamics. Study 2: homoarginine and creatine-deficiency\u2014as before, but AGAT\u2212\/\u2212 mice were given creatine-supplemented diet until 1 week post-MI, when 50% were changed to a creatine-free diet. Both groups therefore had low homoarginine levels, but one group also developed lower myocardial creatine levels. In both studies, all groups had LV remodelling and dysfunction commensurate with the development of chronic heart failure, for example, LV dilatation and mean ejection fraction &amp;lt;20%. However, neither homoarginine deficiency alone or in combination with creatine deficiency had a significant effect on mortality, LV remodelling, or on any indices of contractile and lusitropic function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low levels of homoarginine and creatine do not worsen chronic heart failure arguing against a major causative role in disease progression. This suggests that it is unnecessary to correct hArg deficiency in patients with heart failure, although supra-physiological levels may still be beneficial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14183","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T10:48:30Z","timestamp":1664534910000},"page":"189-199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Homoarginine and Creatine Deficiency do not Exacerbate Murine Ischaemic Heart Failure"],"prefix":"10.1093","volume":"10","author":[{"given":"Debra J.","family":"McAndrew","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]},{"name":"British Heart Foundation Centre for Research Excellence, University of Oxford , Oxford ,","place":["UK"]},{"name":"Wellcome Centre for Human Genetics , Roosevelt 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