Background

Mutations in filamin-C (FLNC) are involved in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM), and have been associated with a left ventricular (LV) phenotype, characterized by nonischemic LV fibrosis, ventricular arrhythmias, and sudden cardiac death (SCD).

Objective

The purpose of this study was to investigate the prevalence of FLNC variants in a gene-negative ACM population and to evaluate the clinical phenotype and SCD risk factors in FLNC-associated cardiomyopathies.

Methods

ACM probands who tested negative for mutations in ACM-related genes underwent FLNC genetic screening. Clinical and genetic data were collected and pooled together with those of previously published FLNC-ACM and FLNC-DCM patients.

Results

In a cohort of 270 gene-elusive ACM probands, 12 (4.4%) had FLNC variants, and 13 additional family members carried the same mutation. Eighteen FLNC variant carriers (72%) had a diagnosis of ACM (72% male; mean age 45 years). On pooled analysis, 145 patients with FLNC-associated cardiomyopathies were included. Electrocardiographic (ECG) low QRS voltages were detected in 37%, and T-wave inversion (TWI) in inferolateral/lateral leads in 24%. Among 67 patients who had cardiac magnetic resonance (CMR), LV nonischemic late gadolinium enhancement (LGE) was found in 75%. SCD occurred in 28 patients (19%), 15 of whom showed LV nonischemic LGE/fibrosis. Compared with patients with no SCD, those who experienced SCD more frequently had inferolateral/lateral TWI (P = .013) and LV LGE/fibrosis (P = .033).

Conclusion

Clinical phenotype of FLNC cardiomyopathies is characterized by late-onset presentation and typical ECG and CMR features. SCD is associated with the presence of LV LGE/fibrosis but not with severe LV systolic dysfunction.

中文翻译：

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细丝蛋白-C 变异相关心肌病：对个体患者数据的汇总分析，以评估临床特征和心源性猝死风险

背景

细丝蛋白-C (FLNC)突变参与致心律失常性心肌病 (ACM) 和扩张型心肌病 (DCM) 的发病机制，并与左心室 (LV) 表型相关，其特征是非缺血性 LV 纤维化、室性心律失常和突发性心律失常心源性死亡（SCD）。

客观的

本研究的目的是调查基因阴性 ACM 人群中FLNC变异的患病率，并评估FLNC相关心肌病的临床表型和 SCD 危险因素。

方法

ACM 相关基因突变检测为阴性的 ACM 先证者接受了FLNC基因筛查。临床和遗传数据与先前发表的FLNC- ACM 和FLNC- DCM 患者的数据一起收集和汇总。

结果

在 270 名基因难以捉摸的 ACM 先证者队列中，12 名（4.4%）有FLNC变异，另外 13 名家庭成员携带相同的突变。18 名FLNC变异携带者（72%）被诊断为 ACM（72% 为男性；平均年龄 45 岁）。在汇总分析中，纳入了 145 名FLNC相关心肌病患者。37% 的患者检测到心电图 (ECG) 低 QRS 电压，24% 的下外侧/外侧导联检测到 T 波倒置 (TWI)。在 67 名进行心脏磁共振 (CMR) 的患者中，75% 的患者发现 LV 非缺血性晚期钆增强 (LGE)。28 名患者 (19%) 发生 SCD，其中 15 名患者出现 LV 非缺血性 LGE/纤维化。与没有 SCD 的患者相比，经历 SCD 的患者更频繁地出现下外侧/外侧 TWI（P = .013) 和 LV LGE/纤维化 ( P = .033)。

结论

FLNC 心肌病的临床表型以迟发性表现和典型的 ECG 和 CMR 特征为特征。SCD 与 LV LGE/纤维化的存在有关，但与严重的 LV 收缩功能障碍无关。