{"id":"64f43672e89d","type":"article","url":"https://hartvaat.nl/2026/02/26/cascadescreening-bij-hypertrofische-cardiomyopathie-genotype-positieve-familiele/","title":"Cascadescreening bij hypertrofische cardiomyopathie: genotype-positieve familieleden houden een verhoogd risico","title_en":"Characterising the phenotype and outcomes of cascade-tested relatives of probands with hypertrophic cardiomyopathy","category":"algemeen","category_label":"Algemeen","professions":["cardioloog"],"tags":["cardiovasculaire-genetica","familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening","gedilateerde-cardiomyopathie","gepersonaliseerde-geneeskunde","hypertrofische-cardiomyopathie","iaso-dcm","laminopathie","vrouwen"],"journal":"Open Heart","doi":"http://openheart.bmj.com/cgi/content/short/13/1/e003557?rss=1","source_url":"https://doi.org/http://openheart.bmj.com/cgi/content/short/13/1/e003557?rss=1","authors":["Chaudhry","W. R.","McWilliam","C.","Berg","J.","Choy","A.-M."],"significance":5,"published":"2026-02-26","source_date":"2026-02-26","image":"","kennis":["https://hartvaat.nl/kennis/cardiometabool/diabetes-en-cardiovasculair-risico/","https://hartvaat.nl/kennis/cardiometabool/diabetes-type-1-en-hart/"],"congress":"","summary_en":"In hypertrophic cardiomyopathy (HCM) due to a pathogenic sarcomere variant, cascade screening of relatives is recommended, but outcomes in such relatives are little studied. In this retrospective cohort (64 families, 280 patients, NHS Tayside, 2010-2018), the occurrence of a major adverse cardiac event (MACE) was examined. Asymmetrical septal hypertrophy meeting diagnostic criteria occurred in 35.4% of cascade-tested individuals. The adjusted septal thickness of genotype-positive relatives (13.9 mm) lay between that of probands (22.1 mm) and genotype-negative relatives (12.3 mm). Cardiac event risk was also intermediate: lower than probands but higher than genotype-negative relatives. Genotype-positive cascade-tested relatives thus retain a degree of complication risk, justifying their identification and follow-up.","created":"2026-07-03T10:32:24Z","updated":"2026-07-03T13:31:22Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Bij hypertrofische cardiomyopathie (HCM) door een pathogene sarcomeervariant wordt cascadescreening van familieleden aanbevolen, maar de uitkomsten bij zo geïdentificeerde familieleden zijn weinig onderzocht. In deze retrospectieve cohortstudie (64 families, 280 patiënten, NHS Tayside, 2010-2018) werd gekeken naar het optreden van een majeur cardiaal event (MACE). Asymmetrische septumhypertrofie die aan de diagnostische criteria voldeed, kwam bij 35,4% van de cascade-geteste personen voor. De gecorrigeerde septumdikte van genotype-positieve familieleden (13,9 mm) lag tussen die van de probandi (22,1 mm) en de genotype-negatieve familieleden (12,3 mm) in. Ook het risico op cardiale events was intermediair: lager dan bij de probandi maar hoger dan bij genotype-negatieve familieleden. Genotype-positieve cascade-geteste familieleden houden dus een zeker complicatierisico, wat hun identificatie en follow-up rechtvaardigt.","abstract_original":"<sec><st>Objectives</st>\n<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>\n</sec>\n<sec><st>Methods</st>\n<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>\n</sec>\n<sec><st>Results</st>\n<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>\n</sec>\n<sec><st>Conclusion</st>\n<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>\n</sec>"}