Key result
Higher myocardial DNA damage markers predict lower LVRR and ~63% higher long-term event risk.
Why the study?
Reliable predictors of treatment efficacy in heart failure have been long awaited, and DNA damage has been implicated as a cause of heart failure.
Do myocardial DNA damage markers (%PAR and %γ-H2A.X) predict left ventricular reverse remodeling and long-term clinical outcomes in patients with HFrEF?
Observational (n=175)
Do myocardial DNA damage markers (%PAR and %γ-H2A.X) predict left ventricular reverse remodeling and long-term clinical outcomes in patients with HFrEF?
Myocardial DNA damage markers assessed via endomyocardial biopsy strongly predict reverse remodeling and long-term prognosis in patients with HFrEF.
Answers are grounded in this paper and cite their sources.
Markers of myocardial DNA damage were associated with lower LVRR and higher events in HFrEF; leaves open incremental value for biopsy-based stratification.
BACKGROUND: Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure. OBJECTIVES: The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure. METHODS: The authors performed immunostaining of DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in endomyocardial biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. They calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation. RESULTS: Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X. The ROC analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (AUCs: 0.867 and 0.855, respectively). There was a negative correlation between the mean proportion of DNA damage marker-positive nuclei and the probability of LVRR across different underlying diseases. In addition, patients with higher %PAR or %γ-H2A.X had more long-term clinical events (PAR HR: 1.63 [95% CI: 1.31-2.01]; P < 0.001; γ-H2A.X HR: 1.48 [95% CI: 1.27-1.72]; P < 0.001). CONCLUSIONS: DNA damage determines the consequences of human heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of heart failure patients with various underlying etiologies.
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Dai et al. (2023) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=175). Myocardial DNA damage markers (%PAR and %γ-H2A.X) was evaluated on Left ventricular reverse remodeling (LVRR) at 1 year (AUC 0.867 (%PAR), AUC 0.855 (%γ-H2A.X)). Higher myocardial DNA damage markers (%PAR and %γ-H2A.X) predicted lower probability of LVRR (AUCs 0.867 and 0.855) and increased risk of long-term clinical events (PAR HR 1.63; 95% CI 1.31-2.01).
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