title: A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.
abstract: BACKGROUND
  Accurate prediction of both mortality and morbidity is of significant importance, but it is challenging in patients with severe heart failure. It is especially difficult to detect the optimal time for implanting mechanical circulatory support devices in such patients. We aimed to analyze the morphometric ultrastructure of nuclear chromatin in cardiomyocytes by developing an original clinical histopathological method. Using this method, we developed a biomarker to predict poor outcome in patients with dilated cardiomyopathy (DCM).
  
  
  RESULTS
  As a part of their diagnostic evaluation, 171 patients underwent endomyocardial biopsy (EMB). Of these, 63 patients diagnosed with DCM were included in this study. We used electron microscopic imaging of cardiomyocyte nuclei and an automated image analysis software program to assess whether it was possible to detect discontinuity of the nuclear periphery. Twelve months after EMB, all patients with a discontinuous nuclear periphery (Group A, n = 11) died from heart failure or underwent left ventricular assist device (VAD) implantation. In contrast, in patients with a continuous nuclear periphery (Group N, n = 52) only 7 patients (13%) underwent VAD implantation and there were no deaths (p<0.01). We then evaluated chromatin particle density (Nuc-CS) and chromatin thickness in the nuclear periphery (Per-CS) in Group N patients; these new parameters were able to identify patients with poor prognosis.
  
  
  CONCLUSIONS
  We developed novel morphometric methods based on cardiomyocyte nuclear chromatin that may provide pivotal information for early prediction of poor prognosis in patients with DCM.
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Machiko
authors: M
authors: Kanzaki
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yoshihiro
authors: Y
authors: Asano
authors: Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Hatsue
authors: H
authors: Ishibashi-Ueda
authors: Center for Medical Research and Education, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Eiji
authors: E
authors: Oiki
authors: Research Center for Ultra-High Voltage Electron Microscopy, Osaka University, Osaka, Japan.
authors: Tomoki
authors: T
authors: Nishida
authors: Department of Cardiovascular Science and Technology, Kyoto Prefectural University School of Medicine, Kyoto, Japan.
authors: Hiroshi
authors: H
authors: Asanuma
authors: Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Hisakazu
authors: H
authors: Kato
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Toru
authors: T
authors: Oka
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Tomohito
authors: T
authors: Ohtani
authors: Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Osamu
authors: O
authors: Tsukamoto
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Shuichiro
authors: S
authors: Higo
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Hidetaka
authors: H
authors: Kioka
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Ken
authors: K
authors: Matsuoka
authors: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yoshiki
authors: Y
authors: Sawa
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Issei
authors: I
authors: Komuro
authors: Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Masafumi
authors: M
authors: Kitakaze
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Seiji
authors: S
authors: Takashima
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yasushi
authors: Y
authors: Sakata
mesh_terms: D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000401:mortality* / Q000601:surgery; D002467:Cell Nucleus / Q000473:pathology*; D002843:Chromatin / Q000648:ultrastructure*; D055032:Electron Microscope Tomography; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality* / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000166:cytology*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002843:Chromatin