Steinmetz Michael, Krause Ulrich, Lauerer Peter, Konietschke Frank, Aguayo Randolph, Ritter Christian Oliver, Schuster Andreas, Lotz Joachim, Paul Thomas, Staab Wieland
Department of Pediatric Cardiology, University Medical Center, Georg-August-University, Goettingen, Germany.
German Center for Cardiovascular Research (DZHK) Partnersite Goettingen, Goettingen, Germany.
Pediatr Cardiol. 2018 Aug;39(6):1156-1164. doi: 10.1007/s00246-018-1875-y. Epub 2018 May 12.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially lethal disease that is well described in adults. In pediatric patients, however, identification of patients at risk of adverse events of ARVC remains a challenge. We aimed to determine which criteria of the revised Task Force Criteria (rTFC), alone or combined, have an impact on diagnosis of ARVC when compared to disease-specific genetic mutations in pediatric patients ≤ 18 years. Between September 2010 and December 2013, 48 consecutive young patients ≤ 18 years of age (mean 14, range of 12.9-15.1 years) underwent contrast-enhanced magnetic resonance imaging (CMR), genetic testing, and comprehensive clinical work-up for ARVC criteria to test for clinically suspected ARVC. As specified by the rTFC, patients were grouped into four categories: "definite," "borderline," "possible," and "none" ARVC. Of the 48 patients, 12 were found to have gene mutations of either the desmoplakin (9/12) or plakophilin (3/12) locus. According to rTFC 12/48 patients were considered as "definite" ARVC (25%), while 10/12 (83.3%) had an ARVC-specific gene mutation. Of the remaining 36 patients, 6 (12.5%) were grouped as "borderline" ARVC, 7 (14.6%) as "possible" ARVC (including the remaining two genetic mutations), and 22 (45.8%) as "none" ARVC, respectively. Statistical analysis of ARVC criteria in patients diagnosed with "definite" ARVC revealed high prevalence of positive findings by imaging (CMR and echocardiography) and positive genetics. The positive predictive value to detect "definite" ARVC by genotyping was 83.3%, while the negative predictive value was 94%. Logistic regression analyses for different criteria combinations revealed that imaging modalities (echo and CMR combined) and abnormalities of 12-lead ECG were significant markers (p < 0.01). Positive results of endomyocardial biopsies or arrhythmia on ECG or Holter as defined by the rTFC were not significant in this analysis. The rTFC for ARVC should be used with caution in children and adolescents suspected for ARVC. 12-Lead ECG and imaging modalities (CMR and echo) were of major value, positive results should prompt genetic testing.
致心律失常性右室心肌病（ARVC）是一种在成人中已有充分描述的潜在致命性疾病。然而，在儿科患者中，识别有ARVC不良事件风险的患者仍然是一项挑战。我们旨在确定与18岁及以下儿科患者的疾病特异性基因突变相比，修订的工作组标准（rTFC）的哪些标准单独或联合使用对ARVC的诊断有影响。在2010年9月至2013年12月期间，48名连续的18岁及以下年轻患者（平均14岁，范围12.9 - 15.1岁）接受了对比增强磁共振成像（CMR）、基因检测以及针对ARVC标准的全面临床检查，以检测临床疑似的ARVC。根据rTFC的规定，患者被分为四类：“确诊”、“临界”、“可能”和“无”ARVC。在这48名患者中，发现12名患者存在桥粒斑蛋白（9/12）或盘状球蛋白（3/12）位点的基因突变。根据rTFC，12/48名患者被视为“确诊”ARVC（25%），而10/12（83.3%）有ARVC特异性基因突变。在其余36名患者中，分别有6名（12.5%）被归类为“临界”ARVC，7名（14.6%）为“可能”ARVC（包括其余两个基因突变），22名（45.8%）为“无”ARVC。对诊断为“确诊”ARVC的患者的ARVC标准进行统计分析显示，影像学检查（CMR和超声心动图）阳性结果和基因检测阳性的患病率很高。通过基因分型检测“确诊”ARVC的阳性预测值为83.3%，而阴性预测值为94%。对不同标准组合的逻辑回归分析显示，影像学检查方式（超声心动图和CMR联合）和12导联心电图异常是显著标志物（p < 0.01）。在该分析中，rTFC定义的心肌内膜活检阳性结果或心电图或动态心电图监测中的心律失常并不显著。对于疑似ARVC的儿童和青少年，应谨慎使用ARVC 的rTFC。12导联心电图和影像学检查方式（CMR和超声心动图）具有重要价值，阳性结果应促使进行基因检测。
