扩张型心肌病患者经心肌活检联合评估心肌炎症和纤维化的临床影响：一项多中心回顾性队列研究
Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study.
作者信息
Nakayama Takafumi, Ogo Keiko Ohta, Sugano Yasuo, Yokokawa Tetsuro, Kanamori Hiromitsu, Ikeda Yoshihiko, Hiroe Michiaki, Hatakeyama Kinta, Ishibashi-Ueda Hatsue, Nakamura Kazufumi, Dohi Kaoru, Anzai Toshihisa, Seo Yoshihiro, Imanaka-Yoshida Kyoko
机构信息
Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Japan.
出版信息
Open Heart. 2025 Mar 12;12(1):e003250. doi: 10.1136/openhrt-2025-003250.
BACKGROUND
Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.
METHODS
This retrospective and multicentre study included patients with DCM-defined as LVEF of ≤45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson's Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3 T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of>5.9% by the Youden's index. The primary endpoint was cardiac death or left ventricular assist device implantation.
RESULTS
A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3 cell count was 8.3/mm. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3 cell count and CAF were independent determinants of the primary endpoint. Kaplan-Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm² (low); 13 of 13.1-23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was >5.9%.
CONCLUSIONS
Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM.
背景
在扩张型心肌病（DCM）患者中，心肌炎症和纤维化是临床预后不良的危险因素。在此，我们研究了使用心肌活检样本评估的这两个因素的联合预后价值。
方法
这项回顾性多中心研究纳入了DCM患者，定义为左心室射血分数（LVEF）≤45%且左心室舒张直径>预测值的112%，无继发性或缺血性心肌病证据。在心肌活检样本中，使用免疫组织化学计数炎性细胞，并进行Masson三色染色以将心肌纤维化定量为胶原面积分数（CAF）。较高的心肌炎症定义为白细胞≥14/mm²，包括≤4个单核细胞/mm²，CD3 T淋巴细胞≥7/mm²。更大的心肌纤维化定义为根据约登指数CAF>5.9%。主要终点是心源性死亡或植入左心室辅助装置。
结果
共纳入了255例DCM患者（平均年龄53.1岁；78%为男性）。在该队列中，平均LVEF为28.0%，平均CAF为10.7%，CD3细胞计数中位数为8.3/mm。在2688天的中位随访期内，46例患者达到主要终点。多变量Cox比例风险分析显示，CD3细胞计数和CAF是主要终点的独立决定因素。Kaplan-Meier分析表明，心肌炎症较高且纤维化程度较大的患者预后最差（对数秩检验p<0.001）。当心肌炎症分为三个等级之一：T淋巴细胞<13/mm²（低）；13至13.1-23.9/mm²（中）；以及T淋巴细胞≥24/mm²（高）时，炎症程度为中度的患者在CAF≤5.9%时生存率较高，但在CAF>5.9%时生存率较低。
结论
经活检证实心肌炎症较高且纤维化程度较大预示着DCM患者的临床预后最差。
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