Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardiomyopathy

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Highlights • Patients with dilated cardiomyopathy who achieved LVRR have a favorable prognosis, but it is still difficult to precisely predict LVRR in the clinical setting. • Immunostaining of DNA damage markers such as PAR in biopsy specimens from patients with dilated cardiomyopathy revealed that patients with LVRR showed a significantly smaller proportion of PAR-positive nuclei compared with those without LVRR. • The high proportion of PAR-positive nuclei was an independent prognostic factor for LVRR. Besides, it can predict clinical prognosis (death, heart transplantation, and ventricular assist device implantation) with good sensitivity and specificity.
Summary This study evaluated myocardial nuclear staining for the DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in 58 patients with dilated cardiomyopathy. Patients with left ventricular reverse remodeling (LVRR) showed a significantly smaller proportion of PAR-positive nuclei and γ-H2A.X–positive nuclei in biopsy specimens compared with those without LVRR. Propensity analysis showed that the proportion of both PAR-positive and γ-H2A.X–positive nuclei were independent prognostic factors for LVRR. In conclusion, we showed the utility of DNA damage-marker staining to predict the probability of LVRR, thus revealing a novel prognostic predictor of medical therapy for dilated cardiomyopathy.