Cardiomyocyte deoxyribonucleic acid damage and cardiac recovery in paediatric dilated cardiomyopathy

Area of Science:

• Cardiology
• Pediatric Cardiology
• Biomarkers

Background:

• Dilated cardiomyopathy (DCM) in pediatric patients often requires mechanical circulatory support.
• The Berlin Heart EXCOR is a ventricular assist device used as a bridge to recovery or transplantation.
• Predicting recovery in low-weight pediatric patients with DCM is clinically significant.

Purpose of the Study:

• To evaluate the clinical significance of the deoxyribonucleic acid (DNA) damage response marker, phosphorylated H2A histone variant X, as a predictor of recovery in pediatric patients with DCM on Berlin Heart EXCOR support.
• To identify factors associated with cardiac functional recovery after EXCOR explant in low-weight pediatric DCM patients.

Main Methods:

• Retrospective review of consecutive pediatric DCM patients who received a Berlin Heart EXCOR between 2013 and 2021.
• Classification of patients into low and high DNA damage groups based on phosphorylated H2A histone variant X expression in cardiomyocytes.
• Comparison of preoperative factors and histological findings between the two groups.

Main Results:

• The incidence of EXCOR explant was 40% at 1-year post-implantation in the study cohort (n=18).
• Significant left ventricular functional recovery was observed at 3 months post-implant in the low DNA damage group.
• Higher percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was significantly associated with improved cardiac recovery and successful EXCOR explant (HR, 0.16; P=0.0096).

Conclusions:

• The degree of DNA damage response to EXCOR implantation may serve as a predictive marker for bridge to recovery in pediatric DCM patients.
• Phosphorylated H2A histone variant X is a potential biomarker for assessing recovery potential in pediatric DCM patients supported by mechanical circulatory support.