Abstract

Abstract Background Asymmetric and symmetric dimethylarginine (ADMA and SDMA) are post-translationally modified amino-acids that inhibit nitric oxide (NO) production and have been associated with cardiovascular events and death. Recently, an association of ADMA with atrial fibrillation (AF) incidence and prevalence has been described. In this study we analyzed the association of ADMA and SDMA with the progression and recurrence of AF. Methods In total, 254 patients (64±11 years, 67% males, BMI 29±8 kg/m2, 53% paroxysmal AF, 27% low voltage areas (LVA)) undergoing first AF ablation were included into analyses. LVA were determined using high-density maps and defined as <0.5 mV. AF progression was defined as paroxysmal AF (PAF) with/without LVA and continuous AF (CAF) with/without LVA. AF recurrences were defined as any atrial arrhythmia occurring after ablation 3 to 18 months. Blood plasma samples were collected before catheter ablation and at follow-up. ADMA and SDMA were measured in plasma samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results While no differences were detected for ADMA, the SDMA plasma concentrations were significantly higher in AF patients with CAF and LVA (n=50, median 0.587 μmol/L; inter quartile range (IQR) 0.514–0.689 μmol/L, p=0.029) compared to PAF without LVA (n=90, 0.532; IQR 0.467–0.640 μmol/L), PAF with LVA (n=12, 0.494; IQR 0.444–0.615 μmol/L) and CAF without LVA (n=86, 0.537; IQR 0.465–0.633) μmol/L. There were 28 patients with available follow-up data and 18 patients (64%) had sinus rhythm. These patients had significantly lower SDMA plasma concentrations (0.458; IQR 0.405–0.517 vs. 0.507; IQR 0.449–0.604 μmol/L; p<0.001) at follow-up, while baseline SDMA levels were similar compared with patients with AF recurrence (p=0.944). Furthermore, patients without recurrence had significantly lower ADMA plasma concentrations (0.466; IQR 0.422–0.520 vs. 0.545; IQR 0.456–0.608 μmol/L, p<0.03) at follow-up, while baseline ADMA levels were similar independent on rhythm outcome (p=0.759). Conclusion Increased SDMA levels correlated with AF progression phenotypes characterized by persistent AF and the presence of LVA. In patients without arrhythmia recurrences ADMA and SDMA levels decreased.

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