Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf Hamburg Germany.
Clinic for Neurology University of Göttingen Germany.
J Am Heart Assoc. 2024 Sep 3;13(17):e034994. doi: 10.1161/JAHA.124.034994. Epub 2024 Aug 27.
Atrial fibrillation (AF) is a stroke risk factor that often remains undetected at hospital admission. Long-term Holter monitoring helps to identify patients with previously unrecognized AF. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are elevated in AF in cross-sectional studies. We analyzed ADMA, SDMA, and other L-arginine metabolites to assess their association with AF in the Find-AF trial.
We included 280 patients presenting with acute cerebral ischemia. Patients presenting in sinus rhythm received 7-day Holter-ECG. Biomarkers were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. We also analyzed protein methylation and L-arginine-related metabolites in human induced pluripotent stem cell-derived cardiomyocytes in vitro. ADMA and SDMA were elevated in 44 patients who presented with AF. SDMA, but not ADMA, was significantly elevated in patients newly diagnosed with AF in Holter-ECG as compared with those in sinus rhythm. SDMA plasma concentration >0.571 μmol/L significantly predicted presence of AF in Holter-ECG (area under the curve=0.676 [0.530-0.822]; =0.029; sensitivity 0.786, specificity 0.572). SDMA levels further increased in patients with AF during the first 24 hours in hospital, and ADMA levels remained stable. In vitro, induced pluripotent stem cell-derived cardiomyocytes showed increased symmetric protein methylation and elevated SDMA during rapid pacing (2.0 Hz versus 0.5 Hz), whereas asymmetric protein methylation and ADMA were unchanged.
SDMA at admission was significantly elevated in stroke patients presenting with AF and showed a moderate but significant prospective association with previously unrecognized AF. Thus, stroke patients with elevated SDMA concentration at admission may specifically benefit from extended Holter-ECG monitoring.
心房颤动（AF）是中风的一个危险因素，在入院时常常未被发现。长期动态心电图监测有助于发现以前未被识别的 AF 患者。在横断面研究中，不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）在 AF 中升高。我们分析了 ADMA、SDMA 和其他 L-精氨酸代谢物，以评估它们在 Find-AF 试验中与 AF 的关系。
我们纳入了 280 名因急性脑缺血而就诊的患者。窦性节律的患者接受了 7 天的动态心电图监测。通过超高效液相色谱-串联质谱法对生物标志物进行定量分析。我们还分析了体外人诱导多能干细胞衍生心肌细胞中的蛋白质甲基化和 L-精氨酸相关代谢物。在 44 名出现 AF 的患者中，ADMA 和 SDMA 升高。与窦性节律患者相比，在动态心电图中首次诊断为 AF 的患者中，SDMA 明显升高，但 ADMA 没有升高。SDMA 血浆浓度>0.571μmol/L 显著预测动态心电图中 AF 的存在（曲线下面积=0.676[0.530-0.822]；=0.029；敏感性 0.786，特异性 0.572）。在入院后 24 小时内，AF 患者的 SDMA 水平进一步升高，而 ADMA 水平保持稳定。在体外，诱导多能干细胞衍生的心肌细胞在快速起搏（2.0Hz 与 0.5Hz）时表现出对称蛋白甲基化增加和 SDMA 升高，而不对称蛋白甲基化和 ADMA 不变。
入院时 SDMA 在出现 AF 的中风患者中显著升高，与以前未被识别的 AF 具有中度但显著的前瞻性关联。因此，入院时 SDMA 浓度升高的中风患者可能特别受益于延长的动态心电图监测。
