The following is a summary of “Genetic Penetrance in Dilated Cardiomyopathy,” published in the April 2024 issue of Cardiology by Cabrera-Romero et al.

Researchers conducted a prospective study to determine the penetrance of new dilated cardiomyopathy (DCM) diagnosis in genotype-positive (G+) relatives and identify associated factors contributing to DCM development.

They studied 779 genotype-positive (G+) individuals (average age 35.8 ±17.3 years, 59% females, 47% with TTN variants) without DCM at 25 Spanish centers. Time to DCM onset was assessed using Kalpan-Meier analysis, and groups were compared using the log-rank test. Hazard ratios (HRs) were determined using Cox regression for variables associated with DCM development. The proportional hazard assumption was investigated using Schoenfeld residuals. 

The results showed that after a median follow-up of 37.1 months (interquartile range, 16.3-63.8), 85 individuals (10.9%) developed DCM at a rate of 2.9 (95% CI, 2.3-3.5) per 100 person-years. DCM onset and penetrance varied by gene group (log-rank 0.016 and P<0.001). Older age (HR per 1-year increase, 1.02; 95% CI, 1.0-1.04), abnormal electrocardiogram (ECG) (HR, 2.13; 95% CI, 1.38-3.29), sarcomeric gene variants (HR, 1.92, 95% CI, 1.05-3.50), lower LVEF (HR per 1% increase, 0.86; 95% CI, 1.05-3.50), and larger LVEDD (HR per 1 mm increase, 1.10; 95% CI, 1.06-1.13) independently predicted DCM. In those with cardiac magnetic resonance (CMR) and late gadolinium enhancement (LGE) assessment (n=360, 45%), LGE was an additional predictor (HR, 2.52; 95% CI, 1.43-4.45).  

Investigators concluded that almost 11% of G+ relatives developed DCM during a median follow-up of 3 years following a first negative screening. 

Source: acc.org/Latest-in-Cardiology/Journal-Scans/2024/04/24/15/22/penetrance-of-dilated-cardiomyopathy