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Family Screening in Hypertrophic Cardiomyopathy
Quick Takes
- The overall diagnostic yield at baseline screening was 26%, highest in relatives of genotype-positive HCM probands.
- Furthermore, only an additional 4% received a diagnosis during the subsequent 7-year mean follow-up, again with the highest proportion in relatives of genotype-positive probands.
- A baseline maximum wall thickness of ≥10 mm was a strong predictive factor for development of HCM during 7 years of follow-up.
Study Questions:
What is the diagnostic yield of screening relatives of hypertrophic cardiomyopathy (HCM) patients and predictive factors for HCM development during long-term follow-up in relatives from gene-elusive families?
Methods:
The investigators conducted a retrospective cohort study of families screened at clinics for inherited cardiomyopathies in Eastern Denmark, from 2006 to 2023. At the initial consultation of the HCM proband, a three-generation family pedigree was drawn to identify relatives at risk, and cascade screening was commenced. The Kaplan-Meier method was used to estimate the cumulative incidence of developing HCM in relatives both in the overall group and stratified according to defined risk groups, which was compared using a log-rank test and the hazard ratio (HR) from a Cox proportional hazards model.
Results:
The authors included 1,230 relatives (55% female; age, 42 ± 17 years) from 531 families. The combined clinical and genetic yield at baseline was 26% (n = 321). After 7 years (mean) of follow-up (6,762 person-years), 43 (4%) additional relatives developed HCM. The strongest predictors of developing HCM were carrying a likely pathogenic/pathogenic variant (HR, 4.58; 95% confidence interval [CI], 2.50-8.40; p < 0.001) and larger left ventricular maximum wall thickness (MWT) (HR, 2.21 per mm; 95% CI, 1.76-2.77 per mm; p < 0.001). In gene-elusive families, they found that an MWT of ≥10 mm represented the optimal classification threshold for developing HCM (area under the curve, 0.80), with only two (0.4%) relatives from gene-elusive families with an MWT of <10 mm developing HCM during follow-up.
Conclusions:
The authors report that in HCM, the diagnostic yield of a single screening visit was one in four, and the additional yield during 7 years of follow-up was 4%.
Perspective:
This study reports that the overall diagnostic yield at baseline screening was 26%, highest in relatives of genotype-positive HCM probands. Furthermore, only an additional 4% received a diagnosis during the subsequent 7 years of mean follow-up, again with the highest proportion in relatives of genotype-positive probands. A baseline MWT of ≥10 mm was a strong predictive factor for development of HCM during 7 years of follow-up. Importantly, the yield of continued follow-up of relatives from gene-elusive families with an MWT <10 mm at baseline was limited, with only 0.4% developing overt HCM during follow-up, matching the prevalence in the general population. These data suggest the potential for more nuanced tailoring of follow-up protocols of adult relatives based on baseline findings.
Clinical Topics: Arrhythmias and Clinical EP, Genetic Arrhythmic Conditions, Heart Failure and Cardiomyopathies
Keywords: Genetics, Hypertrophic Cardiomyopathy
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