title: Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.
abstract: OBJECTIVE
  Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling.
  
  
  RESULTS
  One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04).
  
  
  CONCLUSIONS
  Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling.
authors.affiliation: Department of Cardiology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.|Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Tomos E
authors.initials: TE
authors.lastname: Walters
authors.affiliation: Department of Cardiology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.|Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kalman
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: Sheila K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: Department of Cardiology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Mearns
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Velkoska
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, VIC, Australia.|Department of Cardiology, The Austin Hospital, Melbourne, VIC, Australia.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D001281:Atrial Fibrillation / Q000097:blood / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D064752:Atrial Remodeling; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005355:Fibrosis; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011446:Prospective Studies; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: ACE2 activity; Atrial fibrillation; Atrial remodelling; Fibrosis