Family Screening for Hypertrophic Cardiomyopathy

Study Questions:

Are current guidelines for screening family members of patients with hypertrophic cardiomyopathy (HCM) adequate to detect early-onset disease?


In a single-center retrospective study, data were analyzed from children <18 years of age who underwent echocardiography for purposes of family screening for HCM. First-degree relatives typically were screened independent of age, although echocardiography sometimes was delayed until 3 years of age to avoid sedation for echocardiography. Phenotype-positive status was defined as echocardiographic maximal left ventricular posterior wall or interventricular septal diameter z-score >2. A major cardiac event (MaCE) was defined as death, sudden cardiac death (SCD), or major cardiac interventions (myectomy, implantable cardioverter-defibrillator [ICD] insertion, cardiac transplantation).


Of 524 children screened, 331 were under 10 years of age; 52 (9.9%) had echocardiographic evidence of HCM and 6 (1.1%) were symptomatic at first screening. The median (interquartile range) age at HCM onset was 8.9 (4.7-13.4) years, and at MaCE was 10.9 (8.5-14.3) years, with a median time from HCM onset to MaCE of 1.5 (0.5-4.1) years. About 52.5% phenotype-positive children and 41% with a MaCE were <10 years old. Only 69% of children with early HCM met guideline-directed early screening criteria. Cox regression identified male gender, family history of SCD, and pathogenic variants in MYH7 or MYBPC3 as a predictor of early-onset HCM and of MaCE.


A third of children not eligible for early screening based on current guidelines had phenotype-positive HCM. MYH7 and MYBC3 mutation-positive patients were at highest risk for developing early HCM and for experiencing a MaCE. The authors concluded that these findings support consideration for earlier clinical and genetic screening in younger family members to identify the subset who might benefit from closer monitoring and intervention.


American College of Cardiology/American Heart Association guidelines recommend starting screening first-degree relatives of patients with HCM at age 12 years, with earlier screening only in the setting of an early growth spurt, family history of SCD, or prior to competitive sports participation; European Society of Cardiology guidelines recommend offering clinical and/or genetic screening from age 10 years, with consideration for earlier screening in families with early-onset malignant disease, the presence of cardiac symptoms, or prior to involvement in demanding physical activity. This single-center, retrospective study suggests that earlier screening identifies a substantial number of children with echocardiographic evidence of HCM, and identifies children at risk for adverse clinical events (although most events were cardiac interventions such as myectomy or ICD implantation, potentially affected by practitioner bias). If these data are reproduced in larger populations involving multiple geographic locations, then consideration should be given to earlier screening of at least some first-degree relatives of patients with HCM.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Exercise

Keywords: Cardiomyopathy, Hypertrophic, Death, Sudden, Cardiac, Defibrillators, Implantable, Diagnostic Imaging, Echocardiography, Exercise, Genetic Testing, Heart Failure, Heart Transplantation, Mutation, Pediatrics, Phenotype

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