Abstract
Arginine, homoarginine (hArg), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) affect nitric oxide metabolism and altered concentrations are associated with cardiovascular morbidity and mortality. We analyzed these metabolites using liquid chromatography–tandem mass spectrometry in patients with atrial fibrillation (AF) (n = 241) with a focus on heart rhythm at blood withdrawal, AF progression phenotypes, and successful sinus rhythm (SR) restoration (n = 22). AF progression phenotypes were defined as paroxysmal AF with/without low voltage areas (LVA) and persistent AF with/without LVA. While arginine, ADMA, and hArg were within reference limits for healthy controls, SDMA was higher in the AF cohort (0.57 ± 0.12 vs. 0.53 μmol/L (97.5th percentile in reference cohort)). SR restoration in AF patients resulted in normalization of SDMA concentrations (0.465 ± 0.082 vs. 0.570 ± 0.134 μmol/L at baseline, p < 0.001). Patients with AF at the time of blood sampling had significantly lower hArg (1.65 ± 0.51 vs. 1.85 ± 0.60 μmol/L, p = 0.006) and higher ADMA concentrations (0.526 ± 0.08 vs. 0.477 ± 0.08 μmol/L, p < 0.001) compared with AF patients in SR. hArg concentrations were lower in patients with advanced AF progression phenotypes (persistent AF with LVA (p = 0.046)) independent of heart rhythm at blood sampling. Summarizing, arginine metabolism imbalance is associated with AF in general and AF progression and may contribute to associated risk.Key messages• Heart rhythm at blood withdrawal affects ADMA and hArg level in AF patients.• SDMA is higher in AF patients.• SDMA levels normalize after sinus rhythm restoration.• hArg levels decrease in advanced AF progression phenotypes.
Highlights
Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide [1]
It was hypothesized that Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations might be associated with new onset of AF, but a sub-analysis in the community-based Framingham Heart Study could not confirm this relation [11]
While there were no significant sexspecific differences in ADMA and SDMA, hArg concentration was significantly higher in men than in women (1.88 ± 0.59 μmol/L vs.1.54 ± 0.46 μmol/L, p < 0.001)
Summary
Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide [1]. The progression of AF can be characterized by a switch from paroxysmal (PAF) to persistent AF (persAF) [1], and peri-procedural evidence of low voltage areas (LVA) representing pro-fibrotic advanced left atrial (LA) remodeling processes [2, 3]. Higher ADMA and SDMA as well as lower hArg concentrations were found to be associated with an increased cardiovascular mortality risk [10,11,12]. Increased ADMA concentrations are associated with atherosclerosis, renal failure, hypertension, and hypercholesterolemia [13], which are considered common risk factors predisposing for cardiovascular diseases and AF [14]. We introduced a novel concept of AF progression phenotypes based on AF type and presence of LVA [15, 16], which can help to define pathomechanisms underpinned in the AF progression We used this definition to show that patients with PAF without LVA have better biomarker and imaging profiles compared with patients with persAF and LVA [15, 16]
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