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

Toshiyuki Ko; Kanna Fujita; Seitaro Nomura; Yukari Uemura; Shintaro Yamada; Takashige Tobita; Manami Katoh; Masahiro Satoh; Masamichi Ito; Yukako Domoto; Yumiko Hosoya; Eisuke Amiya; Masaru Hatano; Hiroyuki Morita; Masashi Fukayama; Hiroyuki Aburatani; Issei Komuro

doi:10.1016/j.jacbts.2019.05.010

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

JACC Basic Transl Sci. 2019 Sep 25;4(6):670-680. doi: 10.1016/j.jacbts.2019.05.010. eCollection 2019 Oct.

Authors

Toshiyuki Ko¹, Kanna Fujita¹, Seitaro Nomura¹, Yukari Uemura², Shintaro Yamada¹, Takashige Tobita³, Manami Katoh⁴, Masahiro Satoh⁵, Masamichi Ito¹, Yukako Domoto⁶, Yumiko Hosoya¹, Eisuke Amiya¹, Masaru Hatano¹, Hiroyuki Morita¹, Masashi Fukayama⁶, Hiroyuki Aburatani⁴, Issei Komuro¹

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
² Biostatistics Division, Clinical Research Support Center, University of Tokyo Hospital, Tokyo, Japan.
³ Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.
⁴ Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
⁵ Department of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁶ Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Abstract

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.

Keywords: BMI, body mass index; BNP, B-type natriuretic peptide; CI, confidence interval; DAPI, 4′,6-diamidino-2-phenylindole; DCM, dilated cardiomyopathy; DNA damage; IQR, interquartile range; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; LVRR, left ventricular reverse remodeling; NYHA, New York Heart Association; PAR, poly(ADP-ribose); ROC, receiver-operating characteristic; WGA, wheat germ agglutinin; dilated cardiomyopathy; left ventricular reverse remodeling; poly ADP-ribose.