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- W4380795245 abstract "Introduction: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous etiology and diverse clinical outcomes. Hypothesis: We hypothesized that the genotype of RODCM might correlate with left ventricular reverse remodeling (LVRR) and long-term clinical outcomes. Methods: A total of 386 RODCM patients (pts) [age 44±12 years, 277 males (72%), familial in 98 pts (25%)] with a history of symptoms less than six months underwent whole-exome sequencing (WES) where likely-pathogenic and pathogenic (class 4-5) disease-causing variants were identified. LVRR was defined as an improvement in left ventricular ejection fraction to >50% or ≥10% absolute increase, with left ventricular end-diastolic diameter ≤33 mm/m2 or ≥10% relative decrease. In this prospective study, the primary outcome was the first event of all-cause death, heart transplantation or ventricular assist device. The secondary outcome included sudden cardiac death, resuscitated cardiac arrest or treated ventricular tachyarrhythmias. Results: WES detected class 4-5 titin truncated variants ( TTNtv ) in 69 pts (19%), class 4-5 non-titin variants (non- TTN ) (Figure) in 56 pts (14%), variants of unknown significance only in 103 pts (27%) and a negative result in 158 pts (40%). At 12 months, LVRR was assessed in 359 pts and was present in 171 pts (48%). Carriers of class 4-5 non- TTN variants developed LVRR less frequently than subjects with other genetic testing results (28% vs. 51%, p˂0.01). During a median follow-up of 55 months, the primary and secondary outcomes occurred in 79 pts (20%) and 50 pts (13%), respectively. Carriers of class 4-5 non- TTN variants had an increased risk of both primary [HR 2.36 (95% CI 1.32-4.20), p˂0.01] and secondary [HR 3.08 (95% CI 1.42-6.67), p˂0.01] outcomes as compared with genotype-negative pts. In multivariable models, genotype remained a strong predictor of both types of outcome. Conclusions: Among RODCM patients, carriers of class 4-5 non- TTN variants have an increased risk of death and progressive heart failure, and a higher long-term burden of life-threatening ventricular arrhythmias compared to genotype-negative subjects. Funding: Supported by the research grant of the Ministry of Health, Czech Republic: [NV19-08-00122] and IPO 00023001." @default.
- W4380795245 created "2023-06-16" @default.
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- W4380795245 date "2022-11-08" @default.
- W4380795245 modified "2023-10-07" @default.
- W4380795245 title "Abstract 13730: Genotype-Phenotype Correlates in Recent-Onset Dilated Cardiomyopathy and Their Prognostic Implications" @default.
- W4380795245 doi "https://doi.org/10.1161/circ.146.suppl_1.13730" @default.
- W4380795245 hasPublicationYear "2022" @default.
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