Abstract Aims We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study. Methods and results Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5–9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (−0.6%/year vs. −0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47–182.81, P < 0.01). Conclusion More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.

中文翻译：

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先证者和致心律失常性心肌病家族成员的高外显率和相似的疾病进展

摘要 目的我们旨在通过纵向队列研究评估致心律失常性心肌病 (AC) 患者和突变阳性家庭成员的结构进展及其对心律失常结果的影响。方法和结果 结构进展被定义为新工作组成像标准的发展，从纳入到随访，进展率作为成像参数的年度变化。我们纳入了 144 名 AC 患者和家庭成员（48% 女性，47% 先证者，40 ± 16 岁）。在基因诊断和纳入时，58% 的家庭成员患有外显性 AC 疾病。在 7.0 [四分位距 (IQR) 4.5-9.4] 年的随访期间，47% 的未纳入 AC 的家庭成员制定了 AC 标准，导致每年新的 AC 外显率为 8%。通过对 598 次超声心动图检查的混合模型分析，先证者和家庭成员的右心室流出道直径的进展率相似（0.5 毫米/年与 0.6 毫米/年，P = 0.28）。家庭成员的右心室面积分数变化进展率甚至更高（-0.6%/年 vs.-0.8%/年，P < 0.01）。在纳入时没有明显结构性疾病或心律失常病史的 86 名患者中，8 名 (9%) 发生了首次严重室性心律失常事件，其中 7 名 (88%) 伴有结构性进展。调整年龄、性别和先证者状态后，结构性进展与较高的严重室性心律失常事件发生率相关（HR 21.24，95% CI 2.47–182.81，P < 0.01）。结论 超过一半的家族成员在基因诊断时符合 AC 标准，每年 AC 外显率为 8%。