{"id":"80cce10a60a2","type":"article","url":"https://hartvaat.nl/2025/09/09/pathogene-cardiomyopathie-genvarianten-en-prognose-bij-af/","title":"Pathogene cardiomyopathie-genvarianten en prognose bij AF","title_en":"Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation: Results in 18,000 Clinical Trial Participants.","category":"atriumfibrilleren","category_label":"Atriumfibrilleren","professions":["cardioloog"],"tags":["cardiovasculaire-genetica","gepersonaliseerde-geneeskunde","laminopathie"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2025.06.052","source_url":"https://doi.org/10.1016/j.jacc.2025.06.052","authors":["Sean J Jurgens","Giorgio E M Melloni","Shinwan Kany","Larissa Fabritz","Joel T Rämö","Andreas Goette","Frederick K Kamanu","David D Berg","Christina Magnussen","Seung Hoan Choi","Marc P Bonaca","Robert P Giugliano","Benjamin M Scirica","Stephen D Wiviott","Deepak L Bhatt","Philippe Gabriel Steg","Itamar Raz","Eugene Braunwald","James P Pirruccello","Marc S Sabatine","Nicholas A Marston","Paulus Kirchhof","Patrick T Ellinor","Christian T Ruff"],"significance":6,"published":"2025-09-09","source_date":"2025-09-09","image":"","kennis":[],"congress":"","summary_en":"This study of 18,000 AF patients showed that pathogenic cardiomyopathy gene variants are present in a significant proportion and associated with worse prognosis, supporting genetic testing in the AF population for risk stratification.","created":"2026-07-03T10:31:51Z","updated":"2026-07-03T13:30:51Z","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":"Studie onderzocht de prevalentie en prognostische impact van pathogene cardiomyopathie-genvarianten bij AF-patiënten. Genvarianten zijn geassocieerd met slechtere uitkomsten en kunnen genetische screening informeren.","abstract_original":"BACKGROUND: Genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), although data on clinical outcomes for AF patients with such variants remain sparse. OBJECTIVES: We aimed to study the prognostic implication of rare cardiomyopathy-associated pathogenic variants (CMP-PLP) in AF patients from large, well-phenotyped clinical trials. METHODS: CMP-PLP carriers were identified using exome sequencing in 5 multinational trials from the Thrombolysis in Myocardial Infarction study group (ENGAGE AF, FOURIER, SAVOR, PEGASUS, and DECLARE), with replication in the EAST-AFNET-4 trial. Associations with centrally adjudicated outcomes were assessed using logistic and Cox regression, among patients with AF. RESULTS: In 17,190 patients with a history of AF, we identified 421 (2.4%) CMP-PLP carriers. CMP-PLP variants were associated with a history of heart failure (HF) (OR: 1.66; P < 0.0001), most notably for dilated cardiomyopathy-associated variants. CMP-PLP variants were also associated with incident HF hospitalizations (HR: 1.75; 95% CI: 1.34-2.29; P < 0.0001), most notably for hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy variants. CMP-PLP variants were nominally associated with increased risk of cardiovascular death (HR: 1.46; 95% CI: 1.06-2.02; P = 0.02), driven mainly by dilated cardiomyopathy-associated variants. In contrast, CMP-PLP variants were not associated with prevalent (OR: 0.99; P = 0.96) or incident (HR: 0.95; P = 0.84) ischemic stroke, although anticoagulation use was high. In replication, among 1,479 EAST-AFNET-4 participants, CMP-PLP variants were also associated with prevalent HF and incident HF hospitalizations. CONCLUSIONS: In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF hospitalizations and cardiovascular death, but not stroke. These results, collected from large well-phenotyped clinical trials, demonstrate important prognostic implications for cardiomyopathy-associated genetic variants in AF patients."}