Schoonvelde Stephan A C, Alexandridis Georgios M, Price Laura B, Schinkel Arend F L, Hirsch Alexander, Zwetsloot Peter-Paul, Kammeraad Janneke A E, van Slegtenhorst Marjon A, Verhagen Judith M A, de Boer Rudolf A, Michels Michelle
Department of Cardiology, Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Cardiology, Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Int J Cardiol. 2025 Mar 1;422:132951. doi: 10.1016/j.ijcard.2024.132951. Epub 2024 Dec 31.
(i) Investigate the prevalence of hypertrophic cardiomyopathy (HCM) in individuals with pathogenic/likely pathogenic (P/LP) gene variants detected through family cascade testing in relatives, and (ii) evaluate phenotypic progression in genotype-positive phenotype-negative (G+/P-) individuals during follow-up.
From 2000 to 2023, 273 individuals underwent cardiologic evaluation following P/LP variant detection through family screening. Upon initial evaluation, HCM was diagnosed in 128 (47 %) individuals. Comparing with 145 G+/P- individuals, HCM patients were older (48 vs 38 years, p < 0.001) and more likely male (57 % vs 34 %, p < 0.001). During follow-up (median 11 years), 14 (11 %) of the HCM patients died (two from sudden cardiac death), four (3 %) underwent myectomy, 15 (12 %) developed atrial fibrillation and 17 (13 %) required implantable cardioverter-defibrillator implantation (15 primary prevention, 88 %). HCM-related adverse outcomes correlated with younger diagnosis age. During follow-up (median 8 years) of 118 (out of 145) G+/P- subjects with at least one year of follow-up, seven (6 %) individuals (71 % female, diagnosed age 39-77, after median follow-up 6 years) developed HCM (mean maximal wall thickness increasing from 10.2 mm to 13.3 mm). In this G+/P- cohort, significant echocardiographic changes from baseline to last visit were negligible. Over half (56 %) had <1 mm change of maximal wall thickness. No adverse cardiac outcomes occurred.
The initial evaluation was high-yield, with HCM being diagnosed in 47 % of G+ individuals, more frequently in older males. Over a median 8-year follow-up, 6 % of G+/P- individuals developed mild HCM, with no adverse cardiac outcomes. These data support initial screening in all first degree relatives, but (very) low-frequency cardiologic evaluations for G+/P- individuals thereafter.
（i）调查通过家族级联检测在亲属中检测到的携带致病性/可能致病性（P/LP）基因变异的个体中肥厚型心肌病（HCM）的患病率，以及（ii）评估随访期间基因型阳性表型阴性（G+/P-）个体的表型进展。
2000年至2023年，273名个体在通过家族筛查检测到P/LP变异后接受了心脏评估。初次评估时，128名（47%）个体被诊断为HCM。与145名G+/P-个体相比，HCM患者年龄更大（48岁对38岁，p<0.001），男性比例更高（57%对34%，p<0.001）。在随访期间（中位时间11年），14名（11%）HCM患者死亡（2例死于心源性猝死），4名（3%）接受了心肌切除术，15名（12%）发生了心房颤动，17名（13%）需要植入式心律转复除颤器植入（15例一级预防，88%）。HCM相关不良结局与诊断年龄较小相关。在145名G+/P-受试者中的118名（至少随访1年）的随访期间（中位时间8年），7名（6%）个体（71%为女性，诊断年龄39 - 77岁，中位随访6年后）发展为HCM（平均最大壁厚从10.2毫米增加到13.3毫米）。在这个G+/P-队列中，从基线到最后一次就诊的显著超声心动图变化可忽略不计。超过一半（56%）的个体最大壁厚变化<1毫米。未发生不良心脏结局。
初次评估的检出率很高，47%的G+个体被诊断为HCM，在老年男性中更常见。在中位8年的随访中，6%的G+/P-个体发展为轻度HCM，未出现不良心脏结局。这些数据支持对所有一级亲属进行初次筛查，但此后对G+/P-个体进行（非常）低频的心脏评估。
