Peters, Stacey A. and Wright, Leah and Yao, Jess and McCall, Lauren and Thompson, Tina and Thompson, Bryony and Johnson, Renee and Huynh, Quan and Santiago, Celine F. and Trainer, Alison and Perrin, Mark and James, Paul and Zentner, Dominica and Kalman, Jon and Marwick, Thomas H. and Fatkin, Diane (2025) Environmental Risk Factors Are Associated With the Natural History of Familial Dilated Cardiomyopathy. Journal of the American Heart Association, 14 (9). ISSN 2047-9980
Full text not available from this repository.Abstract
Background
Familial dilated cardiomyopathy (DCM) is characterized by marked variability in phenotypic penetrance. The extent to which this is determined by patient‐specific environmental factors is unknown.
Methods and Results
A retrospective longitudinal cohort study was performed in families with DCM‐causing genetic variants. Environmental factors were classified into 2 subsets based on evidence for a causal link to depressed myocardial contractility, termed (1) DCM‐promoting factors and (2) heart failure comorbidities. These factors were correlated with DCM diagnosis and disease trajectory after accounting for relevant confounders and familial relatedness. A total of 105 probands and family members were recruited: 51 genotype positive, phenotype positive, 24 genotype positive, phenotype negative, and 30 genotype negative, phenotype negative. Demographic characteristics were similar between the 3 genotype groups. DCM‐promoting environmental factors (eg, alcohol excess) were enriched in genotype‐positive, phenotype‐positive individuals compared with genotype‐positive, phenotype‐negative ( P <0.001) and genotype‐negative, phenotype‐negative ( P =0.003) individuals and were significantly associated with age at DCM onset (hazard ratio, 2.01; P =0.014). Heart failure comorbidities (eg, diabetes) had a similar prevalence in genotype‐positive, phenotype‐positive and genotype‐negative, phenotype‐negative individuals but were significantly reduced in the genotype‐positive, phenotype‐negative group. Fluctuations in left ventricular ejection fraction during follow‐up were linked to changes in environmental factors in 35 of 45 (78%) of instances: 32 (91%) of these were DCM‐promoting factors.
Conclusions
We identified distinct subsets of environmental factors that affect DCM penetrance and trajectory. Our data highlight DCM‐promoting environmental factors as key determinants of penetrance and natural history. Collectively, these findings provide a new framework for risk factor assessment in familial DCM and have important implications for clinical management.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Oct 2025 04:49 |
| Last Modified: | 31 Oct 2025 04:49 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1720 |
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