Beyond Nature vs Nurture: Modifiers of Genetically Mediated Dilated Cardiomyopathy

Dr Eleanor Rye, University of New South Wales

Postgraduate Scholarship

Years funded: 2025 - 2027

Investigating modifiers of genetic dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure, affecting approximately one in 2500 people and resulting in significant morbidity and mortality. The importance of genetic variants is increasingly recognized, with recent estimates highlighting that up to a quarter of all DCM patients have an underlying genetic basis of disease.

Observational studies have, however, demonstrated significant phenotypic heterogeneity, suggesting that additional factors may modify disease course and that our understanding of inherited cardiomyopathies is incomplete. Several environmental and lifestyle factors have been suggested to modify phenotypic expression, however high-quality evidence is lacking, leaving clinicians and affected patients with little guidance as to how to manage the condition. Further clinical and experimental studies are needed to clarify these gene-environment interactions and better understand how they may exacerbate or attenuate genetic risk.

Exploring early intervention for inherited heart failure

Treatment for DCM is currently limited to generic heart failure therapies, with a focus on symptom control once the disease occurs. This approach disregards the fundamentally different disease mechanism in inherited cardiomyopathies and restricts intervention to late in the disease course when ventricular dysfunction is established. Evidence is lacking regarding the optimal timing and type of therapeutic intervention in high-risk genotypes.

The proposed project will use a combination of clinical and experimental studies to examine gene-environment interactions in high-risk inherited DCM models. Building upon earlier work within our research group, the project will utilise novel preclinical imaging tools to examine the effects of environmental factors in zebrafish cardiomyopathy models and explore the role of early intervention on disease severity. Long term, the translation of project outcomes is expected to guide innovative approaches to the treatment and prevention of heart failure in at-risk individuals.