Cannatà, Antonio and Merlo, Marco and Dal Ferro, Matteo and Barbati, Giulia and Manca, Paolo and Paldino, Alessia and Graw, Sharon and Gigli, Marta and Stolfo, Davide and Johnson, Renee and Roy, Darius and Tharratt, Kevin and Bromage, Daniel I. and Jirikowic, Jean and Abbate, Antonio and Goodwin, Allison and Rao, Krishnasree and Marawan, Amr and Carr-White, Gerry and Robert, Leema and Parikh, Victoria and Ashley, Euan and McDonagh, Theresa and Lakdawala, Neal K. and Fatkin, Diane and Taylor, Matthew R. G. and Mestroni, Luisa and Sinagra, Gianfranco (2022) Association of Titin Variations With Late-Onset Dilated Cardiomyopathy. JAMA Cardiology, 7 (4). p. 371. ISSN 2380-6583
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Abstract
Importance: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). Objective: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. Design, Setting, and Participants: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. Main Outcomes and Measures: The study outcome was all-cause mortality. Results: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. Conclusions and Relevance: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 07 Jun 2022 00:15 |
| Last Modified: | 14 Mar 2023 02:17 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1232 |
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