Cardiomyocyte deoxyribonucleic acid damage and cardiac recovery in paediatric dilated cardiomyopathy

OBJECTIVES The goal of this study was to identify the clinical significance of the deoxyribonucleic acid (DNA) damage response marker, phosphorylated H2A histone variant X, on the bridge to recovery in low-weight paediatric patients with dilated cardiomyopathy (DCM) after having a Berlin Heart EXCOR implanted.METHODS Consecutive paediatric patients with DCM who had an EXCOR implanted for DCM at our hospital between 2013 and 2021 were reviewed. Patients were classified into 2 groups according to the degree of DNA damage in the left ventricular cardiomyocytes-the low DNA damage group and the high DNA damage group-using the median value as the threshold. We examined and compared the preoperative factors and histologic findings associated with cardiac functional recovery following the explant procedure in the 2 groups.RESULTS Competing outcome analysis of 18 patients (median body weight, 6.1 kg) showed that the incidence of an EXCOR explant was 40% at 1 year after the implant procedure. Serial echocardiography revealed significant left ventricular functional recovery in the low DNA damage group 3 months after the implant. The univariable Cox proportional hazards model revealed that the percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was the significant factor associated with cardiac recovery and the EXCOR explant (hazard ratio, 0.16; 95% confidence interval, 0.027-0.51; P = 0.0096).CONCLUSIONS The degree of DNA damage response to the EXCOR implant may aid in predicting the bridge to recovery with EXCOR among low-weight paediatric patients with DCM.

Automated summary

The clinical significance of phosphorylated H2A histone variant X as a marker for DNA damage response was investigated in low-weight paediatric patients with dilated cardiomyopathy (DCM) after Berlin Heart EXCOR implantation. Patients were classified into low DNA damage and high DNA damage groups based on the degree of DNA damage in left ventricular cardiomyocytes. It was found that the low DNA damage group showed significant left ventricular functional recovery 3 months after implantation. The percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was identified as a significant factor associated with cardiac recovery and EXCOR explant.