Key result
More phosphorylated H2AX-positive cardiomyocytes linked to ~84% lower rate of cardiac recovery and EXCOR explant.
Why the study?
To identify the clinical significance of the DNA damage response marker, phosphorylated H2A histone variant X, on bridge to recovery in low-weight paediatric patients with DCM after Berlin Heart EXCOR implantation.
Does the degree of cardiomyocyte DNA damage predict cardiac recovery and EXCOR explant in low-weight paediatric patients with dilated cardiomyopathy?
Cohort (n=18)
No
Does the degree of cardiomyocyte DNA damage predict cardiac recovery and EXCOR explant in low-weight paediatric patients with dilated cardiomyopathy?
Hazard Ratio: 0.16 (95% CI 0.027–0.51)
p-value: p=0.0096
The degree of cardiomyocyte DNA damage, measured by phosphorylated H2A histone variant X, may predict cardiac recovery and successful EXCOR explantation in low-weight pediatric patients with 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.
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Tominaga et al. (2023) conducted a cohort in Dilated cardiomyopathy (n=18). High DNA damage (phosphorylated H2A histone variant X) vs. Low DNA damage was evaluated on Cardiac recovery and EXCOR explant (HR 0.16, 95% CI 0.027-0.51, p=0.0096). The percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was significantly associated with cardiac recovery and EXCOR explant (HR 0.16; 95% CI 0.027-0.51; P=0.0096).
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