# Pathogene cardiomyopathie-genvarianten en prognose bij AF

*geplaatst 2025-09-09 · Atriumfibrilleren · Journal of the American College of Cardiology · doi 10.1016/j.jacc.2025.06.052 · https://hartvaat.nl/2025/09/09/pathogene-cardiomyopathie-genvarianten-en-prognose-bij-af/*

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.

## English: Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation: Results in 18,000 Clinical Trial Participants.

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.

## Abstract (original, from the publication)

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.

Auteurs: 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

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Bron: Journal of the American College of Cardiology, https://doi.org/10.1016/j.jacc.2025.06.052. Bijgewerkt 2026-07-03T13:30:51Z. 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.