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Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases.
Dai, Zhehao; Ko, Toshiyuki; Fujita, Kanna; Nomura, Seitaro; Uemura, Yukari; Onoue, Kenji; Hamano, Momoko; Katoh, Manami; Yamada, Shintaro; Katagiri, Mikako; Zhang, Bo; Hatsuse, Satoshi; Yamada, Takanobu; Inoue, Shunsuke; Kubota, Masayuki; Sawami, Kosuke; Heryed, Tuolisi; Ito, Masamichi; Amiya, Eisuke; Hatano, Masaru; Takeda, Norifumi; Morita, Hiroyuki; Yamanishi, Yoshihiro; Saito, Yoshihiko; Komuro, Issei.
Afiliação
  • Dai Z; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: https://twitter.com/ZhehaoDai_Cards.
  • 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.
  • Fujita K; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • 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.
  • Uemura Y; Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
  • Onoue K; Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan.
  • Hamano M; Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Japan.
  • Katoh M; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Yamada S; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Katagiri M; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Zhang B; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Hatsuse S; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Yamada T; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Inoue S; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Kubota M; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Sawami K; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Heryed T; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Ito M; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • 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.
  • 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.
  • Takeda N; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Morita H; Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • 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.
  • Saito Y; Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan; Nara Prefectural Seiwa Medical Center, Nara Prefectural Hospital Organization, Nara, Japan.
  • 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: komu
JACC Heart Fail ; 12(4): 648-661, 2024 Apr.
Article em En | MEDLINE | ID: mdl-37930291
ABSTRACT

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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Insuficiência Cardíaca Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Insuficiência Cardíaca Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article