复律后全血基因表达区分房颤和窦性心律
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Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion.
背景
心房颤动（AF）患者恢复窦性心律的治疗方案限制了长期复律成功率。 基因表达谱可能提供AF病理生理学的新见解。
通过比较电复律（ECV）前后的全血基因表达来识别生物标志物并改善我们对AF病理生理学的理解。
方 法
在46例持续性房颤患者接受ECV治疗后，在成功复律前1-2小时和复律后4至6周时收集全血样本。 将配对的样品送入基因芯片中和血浆生物标志物进行比较。
结 果
在所测试的13,942个基因中，SLC25A20和PDK4的表达与AF的相关性最强。心脏复律后，SLC25A20和PDK4表达分别下降0.8（CI 0.7-0.8，p = 2.0x10-6）和0.7（CI 0.6-0.8，p = 3.0x10-5）倍。心脏复律后，NT-proBNP浓度中位数从127.7 pg / mL降至44.9 pg / mL（p = 2.3x10-13）。与单独的NT-proBNP相比，结合型NT-proBNP和基因表达（NT-proBNP + SLC25A20曲线下面积= 0.88，NT-proBNP + PDK4AUC = 0.86）的AF辨别模型具有较高的判别能力。此外，与其他模型相比，包括NT-proBNP，SLC25A20和PDK4的模型显着提高AF辨别（AUC = 0.87，净重新分类指数> 0.56，p <5.8x10-3）。我们验证了17名患者独立样本中SLC25A20和PDK4与AF之间的关联性。
结 论
这项研究表明，SLC25A20，PDK4和NT-proBNP作为生物标志物可区分房颤与窦性心律的增量效用。AF期间SLC25A20和PDK4的表达升高表明AF中能量代谢的重要作用。
原始文献摘要
Abstract
Background Treatment to restore sinus rhythm among patients with atrial fibrillation (AF) has limited long-term success rates. Gene expression profiling may provide new insights into AF
pathophysiology.
Objective To identify biomarkers and improve our understanding of AF pathophysiology by comparing whole blood gene expression before and after electrical cardioversion (ECV).
Methods In 46 patients with persistent AF that underwent ECV, whole blood samples were collected 1–2 hours before and 4 to 6 weeks after successful cardioversion. The paired samples were sent for microarray and plasma biomarker comparison.
Results Of 13,942 genes tested, expression of SLC25A20 and PDK4 had the strongest associations with AF. Post-cardioversion, SLC25A20 and PDK4 expression decreased by 0.8 (CI 0.7–
0.8, p = 2.0x10-6) and 0.7 (CI 0.6–0.8, p = 3.0x10-5) fold respectively. Median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations decreased from 127.7 pg/mL to 44.9 pg/mL (p = 2.3x10-13) after cardioversion. AF discrimination models combining NT-proBNP and gene expression (NT-proBNP + SLC25A20 area under the curve = 0.88, NT-proBNP + PDK4 AUC = 0.86) had greater discriminative capacity as compared with NT-proBNP alone (AUC = 0.82). Moreover, a model including NT-proBNP, SLC25A20 and PDK4 significantly improved AF discrimination as compared with other models (AUC = 0.87, Net Reclassification Index >0.56, p<5.8x10-3). We validated the association between SLC25A20 and PDK4 with AF in an independent sample of 17 patients.
Conclusion
This study demonstrates that SLC25A20, PDK4, and NT-proBNP have incremental utility as biomarkers discriminating AF from sinus rhythm. Elevated SLC25A20 and PDK4 expression during AF indicates an important role for energy metabolism in AF
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