Differences in Cardiac Mechanics among Genetically At-Risk First-Degree Relatives: The DCM Precision Medicine Study.

Area of Science:

• Cardiology
• Genetics
• Biomarkers

Background:

• Dilated cardiomyopathy (DCM) risk is high in first-degree relatives (FDRs).
• Early detection of cardiac changes in at-risk FDRs with normal LV size and ejection fraction (LVEF) is crucial.
• The clinical relevance of variants of uncertain significance (VUSs) in DCM remains unclear.

Approach:

• Evaluated LV structure and function using speckle-tracking echocardiography in 124 FDRs of DCM probands.
• Compared LV global longitudinal strain (GLS) across groups: FDRs with pathogenic/likely pathogenic (P/LP) variants, VUSs, and no variants.
• Accounted for age-dependent penetrance in the analysis.

Key Points:

• Older FDRs with P/LP variants or VUSs exhibited significantly lower absolute LV GLS values compared to controls.
• LV GLS reductions were observed even with normal LV size and LVEF.
• These findings suggest that LV GLS can detect subclinical myocardial dysfunction in at-risk individuals.

Conclusions:

• LV GLS is a sensitive marker for identifying a pre-DCM phenotype in genetically at-risk FDRs.
• Some DCM-related VUSs may be clinically relevant and detectable through impaired LV GLS.
• LV GLS has potential utility in risk stratification and early intervention for DCM.