Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome
Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome
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DOI：
10.1161/circulationaha.105.520999
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发表时间：
2005-12-13
期刊：
影响因子：
37.8
通讯作者：
Russo, MA
中科院分区：
文献类型：
--
作者：
Frustaci, A;Priori, SG;Russo, MA
背景：结构性心脏病和钠通道功能障碍在Brugada综合征电不稳定诱导中的作用仍有争议。方法与结果：我们连续研究了18例Brugada综合征患者（男性15例，女性3例，平均年龄42.0±12.4岁），临床表现为Brugada综合征，无创检查心脏结构和功能正常。临床表现为室性颤动7例，持续性多形态室性心动过速7例，晕厥4例。所有患者均行心导管穿刺、冠状动脉和心室血管造影、双心室心肌膜活检和SCN5A基因DNA筛查。对活检样本进行组织学、电子显微镜和病毒基因组分子筛选。7例在右心室发现微动脉瘤，4例在左心室也发现微动脉瘤。组织学显示14例患者普遍或局部右室心肌炎，4例可检测到病毒基因组；右室心肌病1例；心肌病的变化在3。遗传学研究发现了4个SCN5A基因突变的携带者，这些突变导致突变蛋白的体外功能异常。在这些患者中，组织学上存在肌细胞细胞质变性，而末端dUTP缺口末端标记分析显示，与正常对照组相比，右心室和左心室的凋亡肌细胞显著增加（P=0.014和P=0.013）。结论：尽管在无创评估中心脏明显正常，但在所有18例Brugada综合征患者中，心内膜心肌活检均检测到结构改变。18例患者中有4例发现SCN5A基因突变，可能导致心肌细胞隐蔽性结构异常，导致阵发性心律失常表现。
Background-The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated.Methods and Results-We studied 18 consecutive patients (15 males, 3 females; mean age 42.0 +/- 12.4 years) with clinical phenotype of Brugada syndrome and normal cardiac structure and function on noninvasive examinations. Clinical presentation was ventricular fibrillation in 7 patients, sustained polymorphic ventricular tachycardia in 7, and syncope in 4. All patients underwent cardiac catheterization, coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the SCN5A gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes. Microaneurysms were detected in the right ventricle in 7 patients and also in the left ventricle in 4 of them. Histology showed a prevalent or localized right ventricular myocarditis in 14 patients, with detectable viral genomes in 4; right ventricular cardiomyopathy in 1 patient; and cardiomyopathic changes in 3. Genetic studies identified 4 carriers of SCN5A gene mutations that cause in vitro abnormal function of mutant proteins. In these patients, myocyte cytoplasm degeneration was present at histology, whereas terminal dUTP nick end-labeling assay showed a significant increase of apoptotic myocytes in right and left ventricle versus normal controls (P=0.014 and P=0.013, respectively).Conclusions-Despite an apparently normal heart at noninvasive evaluation, endomyocardial biopsy detected structural alterations in all 18 patients with Brugada syndrome. Mutations in the SCN5A gene, identified in 4 of the 18 patients, may have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations.