Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases.

DNA damage heart failure poly(ADP-ribose) reverse remodeling γ-H2A.X

Journal

JACC. Heart failure
ISSN: 2213-1787
Titre abrégé: JACC Heart Fail
Pays: United States
ID NLM: 101598241

Informations de publication

Date de publication:
28 Oct 2023
Historique:
received: 22 06 2023
revised: 27 09 2023
accepted: 28 09 2023
medline: 6 11 2023
pubmed: 6 11 2023
entrez: 6 11 2023
Statut: aheadofprint

Résumé

Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure. The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure. 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. 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]). 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
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 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 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 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.

Identifiants

DOI: 10.1016/j.jchf.2023.09.027 PMID: 37930291
pubmed: 37930291
pii: S2213-1779(23)00680-7
doi: 10.1016/j.jchf.2023.09.027
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures This work was supported by a Japan Society for the Promotion Science (JSPS) Grant-in-Aid for Scientific Research (A) (to Dr Nomura), a JSPS Grant-in-Aid for Scientific Research (S) (to Dr Komuro), a JSPS Grant-in-Aid for JSPS fellows (grant number 23KJ0434 to Dr Dai), the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura), JST FOREST Program (grant number JPMJFR210U to Dr Nomura), Japan Foundation for Applied Enzymology (to Drs Ko and Dai), SENSHIN Medical Research Foundation (to Dr Ko), Merck Sharp & Dohme Life Science Foundation (to Dr Ko), Takeda Science Foundation (to Dr Ko), Japanese Circulation Society (to Dr Ko), Japan Heart Foundation (to Dr Ko), Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), and Japan Agency for Medical Research and Development (AMED) (grant nos. 22ek0109600h0002 to Dr Ko and JP20ek0210141, JP20ek0109487, JP17gm0810013, JP18km0405209, JP19ek0210118, JP21ek0109543, and JP21ek0109569 to Drs Nomura and Komuro). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Zhehao Dai (Z)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: https://twitter.com/ZhehaoDai_Cards.

Toshiyuki Ko (T)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Kanna Fujita (K)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Seitaro Nomura (S)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Frontier Cardiovascular Science, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: senomura-cib@umin.ac.jp.

Yukari Uemura (Y)

Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.

Kenji Onoue (K)

Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan.

Momoko Hamano (M)

Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Japan.

Manami Katoh (M)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Shintaro Yamada (S)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Mikako Katagiri (M)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Bo Zhang (B)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Satoshi Hatsuse (S)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Takanobu Yamada (T)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Shunsuke Inoue (S)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Masayuki Kubota (M)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Kosuke Sawami (K)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Tuolisi Heryed (T)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Masamichi Ito (M)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Eisuke Amiya (E)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Masaru Hatano (M)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Advanced Medical Center for Heart Failure, University of Tokyo Hospital, Tokyo, Japan.

Norifumi Takeda (N)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Hiroyuki Morita (H)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Yoshihiro Yamanishi (Y)

Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Japan; Department of Complex Systems Science, Graduate School of Informatics, Nagoya University, Nagoya, Japan.

Yoshihiko Saito (Y)

Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan; Nara Prefectural Seiwa Medical Center, Nara Prefectural Hospital Organization, Nara, Japan.

Issei Komuro (I)

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Frontier Cardiovascular Science, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; International University of Health and Welfare, Tokyo, Japan. Electronic address: komuro-tky@umin.ac.jp.

Classifications MeSH