Author + information
- Received March 7, 2019
- Revision received May 27, 2019
- Accepted May 28, 2019
- Published online October 28, 2019.
- Toshiyuki Ko, MD, PhDa,∗,
- Kanna Fujita, MDa,∗,
- Seitaro Nomura, MD, PhDa,∗,
- Yukari Uemura, PhDb,
- Shintaro Yamada, MDa,
- Takashige Tobita, MDc,
- Manami Katoh, MD, PhDd,
- Masahiro Satoh, MD, PhDe,
- Masamichi Ito, MD, PhDa,
- Yukako Domoto, MD, PhDf,
- Yumiko Hosoya, MD, PhDa,
- Eisuke Amiya, MD, PhDa,
- Masaru Hatano, MD, PhDa,
- Hiroyuki Morita, MD, PhDa,
- Masashi Fukayama, MD, PhDf,
- Hiroyuki Aburatani, MD, PhDd and
- Issei Komuro, MD, PhDa,∗ ()
- aDepartment of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- bBiostatistics Division, Clinical Research Support Center, University of Tokyo Hospital, Tokyo, Japan
- cDepartment of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
- dGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
- eDepartment of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
- fDepartment of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- ↵∗Address for correspondence:
Dr. Issei Komuro, Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
• 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.
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.
↵∗ Drs. Ko, Fujita, and Nomura contributed equally to this paper and are joint first authors.
This work was supported by grants from a Grant-in-Aid for Young Scientists (to Dr. Ko), the Japan Foundation for Applied Enzymology (to Dr. Nomura), the SENSHIN Medical Research Foundation (to Dr. Nomura), the KANAE Foundation for the Promotion of Medical Science (to Dr. Nomura), MSD Life Science Foundation (to Dr. Nomura), The Tokyo Biomedical Research Foundation (to Dr. Nomura), Astellas Foundation for Research on Metabolic Disorders (to Dr. Nomura), The NOVARTIS Foundation (Japan) for the Promotion of Science (to Dr. Nomura), the Japanese Circulation Society (to Dr. Nomura), a Grant-in-Aid for Scientific Research (B) (to Dr. Nomura), a Grant-in-Aid for Scientific Research (A) (to Dr. Komuro), and AMED (JP19ek0210118, JP19gm6210010, JP19bm0804010, JP19gm0810013, JP19km0405209, JP19bm0704026, JP19ek0109406) (to Drs. Ko, Nomura, Aburatani, and Komuro). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 7, 2019.
- Revision received May 27, 2019.
- Accepted May 28, 2019.
- 2019 The Authors