{"id":"8fff077cd386","type":"article","url":"https://hartvaat.nl/2026/03/31/titine-cardiomyopathie-meestal-dcm-of-linksdominante-acm-met-blijvend-ritmestoor/","title":"Titine-cardiomyopathie: meestal DCM of linksdominante ACM, met blijvend ritmestoornisrisico","title_en":"Genotype-phenotype correlations in patients with pathogenic/likely pathogenic titin variants from the Swiss Arrhythmogenic Cardiomyopathy Registry","category":"algemeen","category_label":"Algemeen","professions":["cardioloog"],"tags":["aficamten","aritmogene-cardiomyopathie","cardiomyopathie-gerichte-therapie","gedilateerde-cardiomyopathie","hypertrofische-cardiomyopathie","iaso-dcm","immunoadsorptie","inflammatoire-cardiomyopathie","laminopathie"],"journal":"Open Heart","doi":"http://openheart.bmj.com/cgi/content/short/13/1/e003750?rss=1","source_url":"https://doi.org/http://openheart.bmj.com/cgi/content/short/13/1/e003750?rss=1","authors":["Scha&#x0308;tti","N. A.","Fokstuen","S.","Medeiros-Domingo","A.","Maccio","U.","Na&#x0308;gele","M. P.","Mikulicic","F.","Flammer","A. J.","Sazgary","L.","Manka","R.","Wilzeck","V. C.","Tanner","F.","Grebmer","C.","Vischer","A. S.","Odening","K. E.","Rieder","M.","Ruschitzka","F.","Brunckhorst","C.","Duru","F.","Saguner","A. M.","Bonetti","N. R."],"significance":5,"published":"2026-03-31","source_date":"2026-03-31","image":"","kennis":["https://hartvaat.nl/kennis/cardiometabool/diabetes-en-cardiovasculair-risico/","https://hartvaat.nl/kennis/coronairlijden/stemi/"],"congress":"","summary_en":"Truncating variants in the titin gene (TTNtv) are associated with cardiomyopathy, mainly dilated cardiomyopathy (DCM); arrhythmogenic phenotypes are scarcely studied. In this Swiss study (46 cardiomyopathy patients with a pathogenic/likely-pathogenic TTNtv; 63% male, median age 47), at baseline 89% met DCM criteria and 17% the revised Padua criteria for arrhythmogenic cardiomyopathy (ACM) — exclusively the left-dominant type, never the ARVC type. Most variants were in the A-band (74%). Under optimal medical therapy, left and right ventricular function improved, yet ventricular arrhythmias in the primary-prevention group still increased over time. Late gadolinium enhancement was usually in the basal septum and was not associated with more arrhythmias; high-grade AV block, unlike in sarcoidosis, did not occur. TTN cardiomyopathy thus presents as DCM or left-dominant ACM, with a persistently high arrhythmia risk despite favourable remodelling.","created":"2026-07-03T10:32:20Z","updated":"2026-07-03T13:31:18Z","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":"Afkappende varianten in het titinegen (TTNtv) zijn geassocieerd met cardiomyopathie, vooral gedilateerde cardiomyopathie (DCM); de aritmogene fenotypes zijn nauwelijks onderzocht. In deze Zwitserse studie (46 cardiomyopathiepatiënten met een (waarschijnlijk) pathogene TTNtv; 63% man, mediane leeftijd 47 jaar) voldeed bij aanvang 89% aan de DCM-criteria en 17% aan de herziene paduacriteria voor aritmogene cardiomyopathie (ACM) — uitsluitend het linksdominante type, nooit het ARVC-type. De meeste varianten lagen in de A-band (74%). Onder optimale medicamenteuze therapie verbeterden de linker- en rechterventrikelfunctie, maar het aantal ventriculaire ritmestoornissen in de primaire-preventiegroep nam toch toe. Late gadolinium-aankleuring zat meestal in het basale septum en hing niet samen met meer ritmestoornissen; hooggradig AV-blok kwam, anders dan bij sarcoïdose, niet voor. TTN-cardiomyopathie presenteert zich dus als DCM of linksdominante ACM, met een blijvend hoog ritmestoornisrisico ondanks gunstige remodellering.","abstract_original":"<sec><st>Background</st>\n<p>Truncating variants in the titin gene (<I>TTNtv</I>) are associated with cardiomyopathy, mainly dilated cardiomyopathy (DCM). The clinical presentation and outcomes of arrhythmogenic phenotypes in these patients are scarcely studied.</p>\n</sec>\n<sec><st>Methods and results</st>\n<p>This was a retrospective Swiss national study including 46 cardiomyopathy patients with pathogenic/likely pathogenic (P/LP) <I>TTNtv</I>. 63% were male and median age at diagnosis was 47 years. At baseline, 89% patients formally fulfilled current DCM criteria and 17% the 2024 revised Padua criteria for diagnosis of ACM, of which all were of the left-dominant phenotype (arrhythmogenic left ventricular cardiomyopathy). No patient fulfilled arrhythmogenic right ventricular cardiomyopathy (ARVC) criteria. Most <I>TTNtv</I> were located on the A-band (74%). Median time to last follow-up (FU) was 63 months. Ventricular arrhythmia (VA) events in the primary prevention group significantly increased over time; although, under optimal guideline-directed medical therapy, mean left ventricular ejection fraction and right ventricular function significantly improved during time to last FU. At the time to last FU, 50% fulfilled DCM criteria, whereas 27% fulfilled the criteria for left-dominant ACM. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) was most commonly in the basal septum, but no patient had higher degree atrioventricular block (AVB). LGE on CMR was not associated with higher rates of VAs.</p>\n</sec>\n<sec><st>Conclusions</st>\n<p>Patients with P/LP <I>TTNtv</I> most frequently present as DCM or left-dominant ACM, whereas <I>TTN</I> is not a classical ARVC-causing gene. The risk of VA remains high despite favourable remodelling. Left ventricular LGE is frequent and often involves the septum. In contrast to sarcoidosis, high degree AVB seems not to be a typical feature of <I>TTN</I> cardiomyopathy.</p>\n</sec>"}