The Yield of Clinical Screening in Pediatric Relatives of Hypertrophic Cardiomyopathy With Negative Genetic Testing.

BACKGROUND

Serial clinical screening of first-degree relatives of individuals with hypertrophic cardiomyopathy (HCM) is recommended. A lower yield of screening in adult relatives with genotype-negative disease might mean a one-off assessment is appropriate, but it is unknown if these findings can be extrapolated to pediatric relatives.

OBJECTIVES

This study aims to determine the yield of clinical screening in pediatric relatives of genotype-negative families.

METHODS

Clinical and outcome data were collected from 404 children (≤18 years) from 227 genotype-positive (G+) families and 292 children from 170 genotype-negative (G-) families referred for family screening.

RESULTS

Individuals from G- families were less likely to have a family history of childhood disease or sudden cardiac death. Over a follow-up of 68.9 ± 49.7 months, a diagnosis was made in 66 (9.5%) individuals with a higher 5-year cumulative incidence in individuals from G+ families than in those from G- families (11.1 [95% CI: 8.3-15.0] vs 4.0 [95% CI: 1.7-9.1]; P = 0.010). A diagnosis was made in 41 (18.1%) G+ families screened compared with 14 (8.2%) G- families (P < 0.001). The age and clinical features at diagnosis did not differ. Over a follow-up of 8.6 ± 4.1 years, there was no difference in the incidence of death or arrhythmic events, but symptoms (19 [36.5%] vs 2 [14.3%]; P = 0.034) and implantable cardioverter-defibrillator implantation (22 [42.3%] vs 1 [7.1%]; P = 0.014) were more common in the G+ group.

CONCLUSIONS

The 5-year cumulative diagnostic yield of screening childhood relatives is twofold higher in G+ families, but a childhood diagnosis was still made in 8% of G- families. These results support the need for universal screening of first-degree childhood relatives with HCM irrespective of genotype status. Further work to determine whether the frequency or timing of screening can be modified is required.