Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study.

backgroundPrevious studies have speculated that a viral infection may act as a trigger in the development of idiopathic dilated cardiomyopathy (DCM) among individuals genetically at risk. This study aims to describe the frequency of patients with DCM who reported experiencing symptoms of flu-like illness before their DCM diagnosis and to examine if this experience modified the association between genetics and DCM.

methodsWe analyzed data from the family-based cross-sectional DCM Study conducted between 2016 and 2021. Self-reported symptoms of flu-like illness proximal to DCM diagnosis were obtained from patient interviews. Exome sequencing identified rare variants (pathogenic, likely pathogenic, or variant of uncertain significance) in DCM genes. In a case-only design, logistic mixed models were used to examine if flu-like illness modified the effect of these rare variants on DCM risk. Firth logistic regression was used to examine if flu-like illness modified the effect of each of 13 400 141 common autosomal variants (minor allele frequency ≥1%) on DCM risk.

resultsOf 1164 patients with DCM, 30.2% reported symptoms of flu-like illness proximal to DCM diagnosis. The percentage of patients with antecedent flu-like illness by variant classification was 30.0% for pathogenic/likely pathogenic, 29.6% for variant of uncertain significance only, and 30.0% for no pathogenic/likely pathogenic/variant of uncertain significance. Antecedent flu-like illness was not found to modify the effect of carrying any pathogenic, likely pathogenic, or variant of uncertain significance variants on DCM risk (interaction relative risk, 0.9 [95% CI, 0.7-1.3]). However, significant modification of the effect of rs2102158 (3q24) by antecedent flu-like illness (

conclusionsApproximately one-third of patients with DCM experienced flu-like illness symptoms before DCM diagnosis. We did not find evidence that a flu-like illness modified the effect of rare variants on DCM risk; however, our genome-wide association study analysis suggested that flu-like illness may modify the effect of a common variant on DCM risk. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.