The genetic architecture of Late-Onset Dilated Cardiomyopathy: an emerging and distinct subtype

Dilated cardiomyopathy (DCM) is a heterogeneous condition defined by left ventricular dilatation and systolic dysfunction¹.  Genetic characterisation of DCM plays an important role in risk stratification and prognosis decisions². There is an emerging cohort of older DCM patients, diagnosed over the age of 60, which may represent a distinct subtype of the condition³. Cannatà et al evaluated the genotype-phenotype relationships of this new demographic in their epidemiological study published in JAMA Cardiology last month.

This retrospective, multi-centre population study investigated 184 DCM patients (56% female, 98% European Ancestry, mean age of diagnosis 67 years) across 7 tertiary centres from Italy, USA, UK and Australia. A high genetic burden (36%) of pathogenic and likely-pathogenic cardiomyopathy genes was identified with significant enrichment of Titin truncating variants (25% of total cases). Gene-positivity predicted poorer outcomes in the primary end point of all-cause mortality: 25% in gene-positive patients Vs 5% negative genetic test (p<0.02).

This study characterises the genetic architecture of late-onset DCM as a distinct subtype with higher prevalence of female sex and increased enrichment of Titin truncating variants. It highlights that in an ageing population, despite accounting for a presumed higher burden of degenerative conditions and comorbidity, genetic aetiologies play an important role and predicts poorer outcomes. This work paves the way for further multi-omic analyses of the late-onset DCM cohort with drive towards a personalised-medicine approach.