Cascadescreening bij hypertrofische cardiomyopathie: genotype-positieve familieleden houden een verhoogd risico

<sec><st>Objectives</st> <p>Cascade-tested relatives of individuals with pathogenic genetic variants in sarcomere genes causing hypertrophic cardiomyopathy are recommended. Little is known about the outcomes in cascade-identified relatives. We aimed to characterise the endpoints for these individuals.</p> </sec> <sec><st>Methods</st> <p>A retrospective cohort case note evaluation of 64 families reviewed by NHS Tayside Clinical Genetics between January 2010 and December 2018 was conducted, identifying 280 patients. The primary endpoint of the study was the composite endpoint of the onset of a repeat major adverse cardiac event (MACE). Analysis of covariance was used to model marginal mean estimates for baseline interventricular size. Cox proportional hazards model was used to depict time to MACEs.</p> </sec> <sec><st>Results</st> <p>Asymmetrical septal hypertrophy fulfilling diagnostic criteria on echocardiography was noted in 35.4% of cascade-tested individuals. Adjusted interventricular septal size for cascade-tested individuals with a positive genotype (13.9 mm; 95% CI (12.1 to 15.8)) was lower than that of probands with a pathogenic variant (22.1 mm; 95% CI (19.7 to 24.4); p&lt;0.001) but higher than that of cascade-tested individuals with no genotype (12.3 mm; 95% CI (10.2 to 14.4); p&lt;0.001). Adjusted multivariate event analysis demonstrated decreased risk of adverse cardiac events in cascade-identified individuals compared with probands with a genotype (HR 4.0; 95% CI (1.9 to 8.5); p&lt;0.001) and increased risk compared with cascade-identified relatives without a genotype (HR 3.3 (1.2 to 9.1); p&lt;0.001).</p> </sec> <sec><st>Conclusion</st> <p>Our results demonstrate that cascade-tested individuals carrying a pathogenic sarcomere variant retain a degree of complication justifying their identification and follow-up.</p> </sec>