The influence of age on the diagnostic yield of genetic testing in dilated cardiomyopathy

Abstract

Abstract Background Dilated cardiomyopathy (DCM) has an estimated population prevalence of 1/250 and is the underlying diagnosis in a third of heart failure patients. A substantial proportion of patients have familial disease caused by dominant mutations in one of more than 50 genes, but clinical practice guidelines recommend genetic testing in young patients with idiopathic DCM. There is an absence of robust data on the influence of age on the diagnostic yield of genetic testing. Methods The study cohort comprised 825 consecutive and unrelated patients (524 male (63.5%)) with DCM who underwent genetic testing from 2015 to 2019. Genetic variants were classified using American College of Medical Genetics (ACMG) criteria. Analyses were stratified by age and sex. Results 173 (20.1%) patients had a positive genetic test (“pathogenic” or “likely pathogenic” variant); 292 (34.4%) had a variant of unknown significance. Mean age at genetic testing was 49.9±14.4 years. Mean age of patients with a positive test was 47.6±13.6 years. 99 (18.9%) men and 67 (22.3%) women had a positive test (p=0.246). Mutations in the TTN gene, encoding for titin, accounted for 46.1% of positive results. 13.8% of mutations were in DSP, 8.4% in RBM20, 6% in FLNC, 4.2% in LMNA, 3.6% in BAG3 and 3.6% in MYH7. There was a trend to declining yield with age (likelihood ratio chi-square p value = 0.047). The yield was 17.2% in the 56–65 year age group and 11.5% above 66 years of age (figure 1). Conclusions Approximately 1 in 5 patients with DCM had a positive genetic test. The yield declined in patients over 66 years but remained above 11%, suggesting that genetic testing should not be confined to younger patients with DCM. Figure 1. Yield of Genetic Testing by Age Funding Acknowledgement Type of funding source: None