Titin-related familial dilated cardiomyopathy: factors associated with disease onset

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dc.contributor.authorJohnson, R.
dc.contributor.authorFletcher, R.A.
dc.contributor.authorPeters, S.
dc.contributor.authorOhanian, M.
dc.contributor.authorSoka, M.
dc.contributor.authorSmolnikov, A.
dc.contributor.authorAbihider, K.E.
dc.contributor.authorAckerman, M.J.
dc.contributor.authorAder, F.
dc.contributor.authorAkhtar, M.M.
dc.contributor.authorAmin, A.S.
dc.contributor.authorAshley, E.A.
dc.contributor.authorAtherton, J.J.
dc.contributor.authorAustin, R.
dc.contributor.authorBaas, A.F.
dc.contributor.authorBagnall, R.D.
dc.contributor.authorRoss, S.B.
dc.contributor.authorBlouin, J.-L.
dc.contributor.authorBrown, E.E.
dc.contributor.authorBundgaard, H.
dc.contributor.authoret al.
dc.date.issued2025
dc.descriptionAvailable online 11 August 2025. OnlinePubl
dc.description.abstractBackground and Aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results: A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions: Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.
dc.description.statementofresponsibilityRenee Johnson ... Eric Haan ... Nicola Poplawski ... et al.
dc.identifier.citationEuropean Heart Journal, 2025; ehaf380-1-ehaf380-18
dc.identifier.doi10.1093/eurheartj/ehaf380
dc.identifier.issn0195-668X
dc.identifier.issn1522-9645
dc.identifier.orcidHaan, E. [0000-0002-7310-5124]
dc.identifier.orcidPoplawski, N. [0000-0002-9372-3325]
dc.identifier.urihttps://hdl.handle.net/2440/147802
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2016822
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1113531
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT2000001
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT2035846
dc.rights© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
dc.source.urihttps://doi.org/10.1093/eurheartj/ehaf380
dc.subjectDilated cardiomyopathy; Titin; Genetics; Risk factors; Prevention
dc.titleTitin-related familial dilated cardiomyopathy: factors associated with disease onset
dc.typeJournal article
pubs.publication-statusPublished online

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