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oai:repisalud.isciii.es:20.500.12105/259032025-12-18T13:00:56Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Stroeks, Sophie L V M author Henkens, Michiel T H M author Dominguez, Fernando author Merlo, Marco author Hellebrekers, Debby M E I author Gonzalez-Lopez, Esther author Dal Ferro, Matteo author Ochoa, Juan Pablo author Venturelli, Francesco author Claes, Godelieve R F author Venner, Max F G H M author Krapels, Ingrid P C author Vanhoutte, Els K author van Paassen, Pieter author van den Wijngaard, Arthur author Sikking, Maurits A author van Leeuwen, Rick author Abdul Hamid, Myrurgia author Li, Xiaofei author Brunner, Han G author Sinagra, Gianfranco author Garcia-Pavia, Pablo author Heymans, Stephane R B author Verdonschot, Job A J author 2024-10-05 Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors. This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID. Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias. The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: -68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years). One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals. JACC Heart Fail. 2024 Oct 5:S2213-1779(24)00617-6. 39425739 https://hdl.handle.net/20.500.12105/25903 autoimmunity dilated cardiomyopathy genetics heart failure systemic immune-mediated disease titin Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease.