Key result
Rare pathogenic variants in DCM genes were associated with an increased risk of death or major adverse cardiac events in individuals with coronary artery disease (HR 1.57; 95% CI 1.22-2.01; p<0.001).
Why the study?
The study was conducted to examine the relevance of genetic and CMR features of dilated cardiomyopathy in individuals with coronary artery disease.
Do rare pathogenic variants in DCM-associated genes increase the risk of death or major adverse cardiac events in patients with coronary artery disease?
Cohort (n=31,607)
Yes
Do rare pathogenic variants in DCM-associated genes increase the risk of death or major adverse cardiac events in patients with coronary artery disease?
Hazard Ratio: 1.57 (95% CI 1.22–2.01)
p-value: p=<0.001
Rare pathogenic variants in DCM-associated genes are associated with adverse left ventricular remodeling and an increased risk of death or MACE in patients with stable coronary artery disease.
May inform CAD risk stratification; leaves open whether genetic screening improves outcomes.
AIMS: To examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD). METHODS AND RESULTS: This study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22-2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4-4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes. CONCLUSION: Rare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.
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Jones et al. (2023) conducted a cohort in Coronary artery disease (n=31,607). Rare pathogenic variants in DCM genes vs. Individuals without rare pathogenic variants in DCM genes was evaluated on Death or major adverse cardiac events (HR 1.57, 95% CI 1.22-2.01, p=<0.001). Rare pathogenic variants in DCM genes were associated with an increased risk of death or major adverse cardiac events in individuals with coronary artery disease (HR 1.57; 95% CI 1.22-2.01; p<0.001).
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