无创检查方法对心肌淀粉样变诊断及预后价值研究

发布时间：2018-04-04 13:23

  本文选题：淀粉样变性　切入点：心肌疾病　出处：《北京协和医学院》2017年博士论文

【摘要】：[研究目的]心肌淀粉样变(cardiac amyloidosis,CA)是由于错误折叠成β片层的前体蛋白,如轻链免疫球蛋白,突变的遗传性甲状腺素运载蛋白,野生型甲状腺素运载蛋白,突变的载脂蛋白,血清淀粉样A蛋白等,异常聚集在胞外基质,不断浸润损伤心肌细胞,最终导致以进行性收缩性和舒张性心力衰竭为主要表现的心脏疾病。由于缺乏特异的临床表现和敏感的无创诊断方法,该病的诊断率低,病死率高,预后差。因此,本研究的目的是总结近五年在本单位诊断为CA患者的临床表现、心电图、超声心动图、心脏核磁共振成像(cardiacmagnetic resonance imaging,CMR)和放射性核素示踪技术等检查的特点,并探讨实验室检查、心电图、超声心动图以及CMR在CA的诊断和评价患者预后的价值。[研究方法]回顾性分析选取2010年1月至2015年2月在北京协和医院住院期间诊断为CA患者的临床症状体征、实验室检查、心电图、超声心动图和CMR、放射性核素示踪检查和病理组织活检的结果,总结CA的临床特点。同时对患者进行电话随访,分别探讨血清游离轻链检测、心电图中假性心肌梗死波形、超声心动图检测的左心房大小和室间隔厚度对CA患者预后的影响,同时通过系统综述和meta分析总结CMR在CA的诊断价值。[研究结果]1.研究纳入128例CA患者,发病年龄较晚,平均(55 ± 12)岁,且多见于男性(79例,61.7%)。患者入院症状各异,以胸闷憋气(44.5%),下肢水肿(36.7%),气短(14.1%),乏力(10.9%),腹泻(9.4%)表现多见。临床分型中轻链型117例(91.4%),其中原发性系统性淀粉样变性84例(65.6%),多发性骨髓瘤伴发32例(25%),其他轻链病相关1例(0.8%),家族性甲状腺素运载蛋白淀粉样变3例(2.3%),不明类型8例(6.3%)。患者心电图以肢体导联低电压(62例,48.4%)、胸导R波递增不良(61例,47.7%)、假性心肌梗死波(57例,44.5%)、ST-T改变(98例,76.6%)为主要表现。超声心动图结果示左心房前后内径增大,室间隔厚度超过12mm的患者共有76例(59.4%),44例(34.4%)患者左心室射血分数小于50%,60例(46.9%)患者E/A比值大于2。左室收缩功能减低50例(39.1%),左室限制性舒张功能减低64例(50%)。24例(18.8%)患者超声心动图出现典型心内膜毛玻璃样改变及颗粒样强回声。15例患者进行了 CMR检查,其中14例均有不同程度的延迟强化。6例CA患者接受了 18F-FDG PET/CT检查,其心肌均未出现放射性摄取增高。2例CA患者进行了 99mTc-MIBI腺苷负荷显像,其中1例心肌可见放射性缺损及减低区。21例99mTc-MDP显像结果中,2例患者软组织摄取增加。诊断淀粉样变性敏感度较高的活检组织部位为肾脏(100%)、舌体(82.6%)、心脏(80%)和齿龈(71.4%)。2.纳入经过血清游离轻链检测的27例CA患者,研究发现无论是采用血清游离轻链浓度差还是克隆性免疫球蛋白轻链κ、λ比值进行分组,高浓度血清游离轻链的患者其生存时间明显短于低浓度血清游离轻链患者。3.研究中36.4%患者心电图中出现心肌梗死波形,并且假性心肌梗死波形与CA预后不良相关,伴有假性心肌梗死波患者的生存时间明显短于缺如的患者(中位生存时间 4 months vs.17 months,p0.001)。4.研究发现左心房增大常见于淀粉样变性出现心脏受累的患者,特别是出现严重心力衰竭、心功能较差的患者。左心房增大可以评价患者预后,是患者进展为严重心力衰竭的危险因素之一。5.22.4%CA患者不伴有室间隔增厚,但是这部分患者的预后与伴有室间隔增厚的患者相同。尽管室间隔厚度不能提供整个队列的预后信息,但是对于不伴有严重心功能不全的患者来说,室间隔厚度增加反而提示患者预后不良。多因素Cox风险比例模型中,NYHA、E/A比值和假性心肌梗死波可以评价预后。6.通过系统综述和meta分析发现CMR延迟钆强化(late gadolinium enhancement,LGE)的诊断敏感性达85%,特异性92%。并且LGE可以区别CA患者和健康对照(阳性似然比为7.481,95%CI:2.835-19.739)。诊断优势比为71.945(95%CI:23.552-219.77)表明CMR鉴别诊断的准确度较高。[结论]临床上心肌淀粉样变患者主要以胸闷憋气、下肢水肿等为临床表现,心电图示肢体导联低电压、胸导R波递增不良和假性心肌梗死波,超声心动图示心室壁增厚伴毛玻璃改变,CMR提示延迟强化。无创检查方法,如血清游离轻链、心电图中假性心肌梗死波形和超声心动图检测的左心房大小能够评价患者预后,同时CMR诊断心肌淀粉样变准确度较高。
[Abstract]:[Objective] cardiac amyloidosis (cardiac amyloidosis CA) is due to misfolded protein precursor beta sheets, such as light chain immunoglobulin, mutation of hereditary transthyretin, wild-type transthyretin mutation, apolipoprotein, serum A protein and starch, abnormal aggregation in the extracellular matrix, continuous infiltration of myocardial injury, resulting in progressive systolic and diastolic heart failure as the main manifestation of heart disease. Because of the lack of specific clinical manifestations and noninvasive diagnostic method is sensitive, the diagnosis rate is low, high mortality rate and poor prognosis. Therefore, the purpose of this study is to summary of recent five years in this unit for the diagnosis of CA patients with clinical manifestations, ECG, echocardiography, cardiac magnetic resonance imaging (cardiacmagnetic resonance, imaging, CMR) and radionuclide tracer technique examination, and to explore the real Laboratory examination, electrocardiogram, echocardiography and CMR in the diagnosis and evaluation of prognosis of patients with CA. The value of research methods] analysis from January 2010 to February 2015 in Peking Union Medical College Hospital during the period of hospitalization for the diagnosis of CA patients with clinical symptoms and signs, laboratory examination, review, electrocardiogram, echocardiography and CMR, radionuclide tracer examination and histopathology biopsy results, summarize the clinical features of CA. At the same time, telephone follow-up of patients, respectively to investigate the serum free light chain detection, pseudo myocardial infarction, electrocardiogram, echocardiography of left atrial size and ventricular septal thickness detection on the prognosis of patients with CA, and through a systematic review and summary of meta CMR CA in the diagnostic value. The results of the study included 128 patients with CA]1. analysis, the late age of onset, the average (55 + 12) years old, and is more common in men (79 cases, 61.7%). The symptoms of the patients on admission 寮，

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