A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.
A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.
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DOI：
10.1371/journal.pone.0148209
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sakata Y
中科院分区：
文献类型：
--
作者：
Kanzaki M;Asano Y;Ishibashi-Ueda H;Oiki E;Nishida T;Asanuma H;Kato H;Oka T;Ohtani T;Tsukamoto O;Higo S;Kioka H;Matsuoka K;Sawa Y;Komuro I;Kitakaze M;Takashima S;Sakata Y
准确预测死亡率和发病率是非常重要的，但它是具有挑战性的严重心力衰竭患者。特别难以检测在此类患者中植入机械循环支持装置的最佳时间。我们的目的是通过发展一种新颖的临床组织病理学方法来分析心肌细胞核染色质的形态计量学超微结构。使用这种方法，我们开发了一种生物标志物来预测扩张型心肌病（DCM）患者的不良结局。作为诊断评估的一部分，171名患者接受了心内膜心肌活检（EMB）。其中，63例诊断为DCM的患者纳入本研究。我们使用心肌细胞核的电子显微镜成像和自动图像分析软件程序来评估是否有可能检测到核周边的不连续性。EMB后12个月，所有核周边不连续的患者（A组，n = 11）死于心力衰竭或接受左心室辅助装置（VAD）植入术。相反，在具有连续核周边的患者（N组，n = 52）中，仅7例患者（13%）接受了VAD植入，并且没有死亡（p<0.01）。然后，我们评估了N组患者的核周围染色质颗粒密度（Nuc-CS）和染色质厚度（Per-CS）;这些新参数能够识别预后不良的患者。我们开发了新的基于心肌细胞核染色质的形态计量学方法，可能为DCM患者预后不良的早期预测提供关键信息。
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). 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. 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.