Carrying a likely pathogenic/pathogenic variant was the strongest predictor of developing hypertrophic cardiomyopathy among relatives (HR 4.58; 95% CI 2.50-8.40; P<0.001).
Cohort (n=1,230)
Yes
Family screening in HCM yields a 26% baseline diagnosis rate, and relatives with a pathogenic variant or baseline maximum wall thickness ≥10 mm are at highest risk of developing HCM during follow-up.
Hazard Ratio: 4.58 (95% CI 2.5–8.4)
p-value: p=<0.001
BACKGROUND Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease, and clinical and genetic family screening is recommended by guidelines. OBJECTIVES This study sought to investigate the diagnostic yield of screening relatives of HCM patients and identify predictive factors for HCM development during long-term follow-up in relatives from gene-elusive families. METHODS This was a retrospective cohort study of families screened at clinics for inherited cardiomyopathies in Eastern Denmark, from 2006 to 2023. RESULTS We 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% 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, we found that an MWT of ≥10 mm represented the optimal classification threshold for developing HCM (area under the curve: 0.80), with only 2 (0.4%) relatives from gene-elusive families with an MWT of <10 mm developing HCM during follow-up. CONCLUSIONS In HCM, the diagnostic yield of a single screening visit was 1 in 4, and the additional yield during 7 years of follow-up was 4%. Gene carriers and relatives from gene-elusive families with a baseline MWT of ≥10 mm were at the highest risk of developing HCM during follow-up. These findings may inform future recommendations on the management of relatives of HCM patients.
“Those who are gene-positive should be followed frequently, as should those who are gene-negative and have an MWT ≥ 10 mm. Those who are gene-negative and have an MWT < 10 mm can be spared follow-up visits or be seen infrequently. The authors suggest that this will decrease healthcare costs and reduce psychological trauma in these relatives.”
Silajdzija et al. (2024) conducted a cohort in Hypertrophic cardiomyopathy (n=1,230). Carrying a likely pathogenic/pathogenic variant vs. Not carrying a pathogenic variant was evaluated on Development of hypertrophic cardiomyopathy (HR 4.58, 95% CI 2.50-8.40, p=<0.001). Carrying a likely pathogenic/pathogenic variant was the strongest predictor of developing hypertrophic cardiomyopathy among relatives (HR 4.58; 95% CI 2.50-8.40; P<0.001).