Oxana Galenko1, Victoria Jacobs1, Stacey Knight1,2, Madisyn Taylor1, Michael J Cutler1, Joseph B Muhlestein1,2, John L Carlquist1, Kirk U Knowlton1,2, T Jared Bunch3,4,5. 1. Intermountain Medical Center Heart Institute, Murray, UT, USA. 2. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. 3. Intermountain Medical Center Heart Institute, Murray, UT, USA. Thomas.bunch@imail.org. 4. Department of Internal Medicine, Stanford University, Palo Alto, CA, USA. Thomas.bunch@imail.org. 5. Intermountain Medical Center Heart Institute, Intermountain Medical Center, 5169 Cottonwood St, Salt Lake City, UT, 84107, USA. Thomas.bunch@imail.org.
Abstract
BACKGROUND: MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRNAs can identify patients with AF and can also help to identify patients at high risk of AF recurrence after ablation. METHODS: Two patient populations were studied: 140 AF cases (93 paroxysmal and 47 persistent) and 50 healthy controls, and 141 AF ablation cases with (n = 86) and without (n = 55) 1-year recurrence. Assessment of several previously identified AF-associated plasma miRNAs (21, 29a, 133a, 133b, 150, 328) was performed with TaqMan assays, using synthetic miRNAs as standards. RESULTS: The AF cases compared to the healthy controls were older and were more often male and hypertensive. After multivariate adjustment, higher miRNA-21 levels significantly decreased the risk of AF (OR = 0.93 per fmol/μl (95% CI = 0.89-0.98, p = 0.007)). There were no significant differences in circulating miRNAs between the AF subtypes of persistent and paroxysmal. Among the AF ablation cases, miRNA-150 was lower for those with AF recurrences at 1 year (adjusted OR = 0.98 per 500,000 fmol/μl; 95% CI = 0.965, 0.998; p = 0.039). CONCLUSIONS: Decreased circulating miRNA-21 is associated with AF, but not with AF subtypes, suggestive that molecular mechanisms responsible for the onset and progression of the AF may be different. Circulating miRNA-150 was significantly associated with a reduction in 1-year AF recurrence post ablation suggestive of adverse structural and electrical remodeling as recurrence mechanisms.
BACKGROUND: MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRNAs can identify patients with AF and can also help to identify patients at high risk of AF recurrence after ablation. METHODS: Two patient populations were studied: 140 AF cases (93 paroxysmal and 47 persistent) and 50 healthy controls, and 141 AF ablation cases with (n = 86) and without (n = 55) 1-year recurrence. Assessment of several previously identified AF-associated plasma miRNAs (21, 29a, 133a, 133b, 150, 328) was performed with TaqMan assays, using synthetic miRNAs as standards. RESULTS: The AF cases compared to the healthy controls were older and were more often male and hypertensive. After multivariate adjustment, higher miRNA-21 levels significantly decreased the risk of AF (OR = 0.93 per fmol/μl (95% CI = 0.89-0.98, p = 0.007)). There were no significant differences in circulating miRNAs between the AF subtypes of persistent and paroxysmal. Among the AF ablation cases, miRNA-150 was lower for those with AF recurrences at 1 year (adjusted OR = 0.98 per 500,000 fmol/μl; 95% CI = 0.965, 0.998; p = 0.039). CONCLUSIONS: Decreased circulating miRNA-21 is associated with AF, but not with AF subtypes, suggestive that molecular mechanisms responsible for the onset and progression of the AF may be different. Circulating miRNA-150 was significantly associated with a reduction in 1-year AF recurrence post ablation suggestive of adverse structural and electrical remodeling as recurrence mechanisms.
Authors: Jan-Thorben Sieweke; Tobias Jonathan Pfeffer; Saskia Biber; Shambhabi Chatterjee; Karin Weissenborn; Gerrit M Grosse; Jan Hagemus; Anselm A Derda; Dominik Berliner; Ralf Lichtinghagen; Denise Hilfiker-Kleiner; Johann Bauersachs; Christian Bär; Thomas Thum; Udo Bavendiek Journal: J Clin Med Date: 2020-04-14 Impact factor: 4.241