Heart failure & cardiomyopathiesCohort study
Impact of Genotype–Phenotype Associations on Prognosis in Dilated Cardiomyopathy
- Multicentre cohort study
Authors' conclusion
Patients with a genetic form of DCM exhibit clinical and genetic heterogeneity. Genotype-based risk stratification is more accurate compared to a phenotype-first approach
Study context
- Population
- Dilated cardiomyopathy (DCM) patients with a (likely) pathogenic variant
- Participants
- 534 patients
- Exposure
- Genotype-first vs phenotype-first approach for prognosis
Main finding
As reported in the abstract
All-cause mortality, HF hospitalization, heart transplantation, malignant ventricular arrhythmias
- Genotype-first: LMNA, FLNC and BAG3 variants had the highest risk for HF and arrhythmogenic adverse outcomes
- Phenotype-first: clusters 3 (low left ventricular ejection fraction (LVEF)) and 4 (arrhythmias, low LVEF) associated with the worst prognosis
- Overall, genotype was the strongest predictor of outcome
Observational data: associations, not effects.
Further findings
Genotype-phenotype associations
- Significant genotype-phenotype associations for 10 genes
- FLNC, LMNA, DSP and PLN variants linked to arrhythmias
- BAG3, TNNT2, DMD and TTN associated with increased cardiac volumes and decreased LVEF
Phenotypic clustering
- Four phenotypic clusters: (1) young, moderately reduced LVEF; (2) arrhythmias, moderate reduced LVEF; (3) low LVEF; (4) arrhythmias, low LVEF
- No clear correlations between phenotypic clusters and genotype
Original publication
Impact of Genotype–Phenotype Associations on Prognosis in Dilated Cardiomyopathy. Eur J Heart Fail. Published 12 September 2025. doi:10.1002/ejhf.70040
Summarised from the published abstract; every number is checked against it