Rudic Boris, Schimpf Rainer, Veltmann Christian, Doesch Christina, Tülümen Erol, Schoenberg Stefan O, Borggrefe Martin, Papavassiliu Theano
1st Department of Medicine, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Mannheim, Germany
1st Department of Medicine, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Mannheim, Germany.
Europace. 2016 Sep;18(9):1411-9. doi: 10.1093/europace/euv300. Epub 2015 Oct 28.
The purpose of the this study was to evaluate a possible genotype-phenotype correlation in BrS patients and to analyze possible associations with clinical events in affected patients. SCN5A gene encodes the alpha-subunit of the voltage-gated sodium channel NaV1.5. Its mutations are associated with a broad spectrum of hereditary arrhythmias such as long-QT syndrome, cardiac conduction diseases, and Brugada syndrome (BrS). Experimental studies have shown an interaction between SCN5A and cellular cytoskeleton, explaining its functional role in cellular integrity of heart cells.
Cardiovascular magnetic resonance was performed on 81 consecutive genetically screened BrS patients and 30 healthy controls. Left ventricular (LV) and right ventricular (RV) volumes and dimensions were assessed and compared with respect to the genotype. Brugada syndrome patients with an SCN5A mutation (16 patients; 20%) revealed significantly larger RV volumes, along with lower RV ejection fraction, than patients without a mutation or controls, indicating a more severe phenotype in patients with a mutation. Furthermore, patients with an SCN5A mutation showed significantly more often a spontaneous type 1 BrS-electrocardiogram (ECG). In multivariate analysis, the presence of a spontaneous type 1 BrS-ECG showed the strongest association with cardiac events. Receiver-operating characteristic curve analysis indicated good predictive performance of RV end-diastolic volume, RV end-systolic, and LV cardiac output (area under the curve = 0.81, 0.81, and 0.2), with respect to the presence of an SCN5A mutation.
Brugada syndrome patients with an SCN5A mutation reveal distinct changes in RV volumes and function when compared with those without an SCN5A mutation. Furthermore, mutation-positive patients have a higher likelihood of a spontaneous type 1 BrS-ECG, which is associated with a higher incidence of clinical events. Cardiovascular magnetic resonance may provide additional insight to distinguish between SCN5A mutation-positive and -negative BrS patients.
本研究旨在评估Brugada综合征（BrS）患者中可能存在的基因型-表型相关性，并分析其与受累患者临床事件的可能关联。SCN5A基因编码电压门控钠通道NaV1.5的α亚基。其突变与多种遗传性心律失常有关，如长QT综合征、心脏传导疾病和Brugada综合征（BrS）。实验研究表明，SCN5A与细胞细胞骨架之间存在相互作用，这解释了其在心脏细胞完整性中的功能作用。
对81例连续接受基因筛查的BrS患者和30例健康对照进行了心血管磁共振检查。评估了左心室（LV）和右心室（RV）的容积和尺寸，并根据基因型进行了比较。与无突变患者或对照组相比，携带SCN5A突变的Brugada综合征患者（16例；20%）的RV容积明显更大，RV射血分数更低，表明突变患者的表型更严重。此外，携带SCN5A突变的患者更常出现自发1型BrS心电图（ECG）。在多变量分析中，自发1型BrS-ECG的出现与心脏事件的关联最强。受试者工作特征曲线分析表明，RV舒张末期容积、RV收缩末期容积和LV心输出量对SCN5A突变的存在具有良好的预测性能（曲线下面积分别为0.81、0.81和0.2）。
与无SCN5A突变的患者相比，携带SCN5A突变的Brugada综合征患者的RV容积和功能有明显变化。此外，突变阳性患者出现自发1型BrS-ECG的可能性更高，这与临床事件的发生率更高有关。心血管磁共振可能为区分SCN5A突变阳性和阴性的BrS患者提供更多见解。
