Association of Titin Variations With Late-Onset Dilated Cardiomyopathy

• DOI: 10.1001/jamacardio.2021.5890
• Publication Date: 2022-02-09T16:07:54Z
• Authors: Antonio Cannatà; Marco Merlo; Matteo Dal Ferro; Giulia Barbati; Paolo Manca; Alessia Paldino; Sharon Graw; Marta Gigli; Davide Stolfo; Renee Johnson; Darius Roy; Kevin Tharratt; Daniel I. Bromage; Jean Jirikowic; Antonio Abbate; Allison Goodwin; Krishnasree Rao; Amr Marawan; Gerry Carr-White; Leema Robert; Victoria Parikh; Euan Ashley; Theresa McDonagh; Neal K. Lakdawala; Diane Fatkin; Matthew R. G. Taylor; Luisa Mestroni; Gianfranco Sinagra
• Keywords: Interquartile range; Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little known about the underpinnings of growing numbers patients with DCM who are diagnosed when they older than 60 years (ie, late-onset DCM).To investigate prevalence, type, prognostic impact disease-associated in DCM.A population had undergone testing 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as presence pathogenic or likely (P/LP) variants.The study outcome all-cause mortality.A total 184 (103 female [56%]; mean [SD] age, 67 [6] years; left ventricular ejection fraction, 32% [10%]) studied. Sixty-six (36%) carriers a P/LP variant. Titin-truncating most prevalent (present 46 [25%] accounting for [69%] all genotype-positive patients). During median (interquartile range) follow-up 42 (10-115) months, 23 (13%) died; 17 (25%) these variants, while 6 (5.1%) genotype-negative.Late-onset might represent distinct subgroup characterized high variation burden, largely due titin-truncating variants. Patients test higher mortality genotype-negative patients. These findings support extended use also