本文選題：淀粉樣變性　切入點(diǎn)：心肌疾病　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文

【摘要】：[研究目的]心肌淀粉樣變(cardiac amyloidosis,CA)是由于錯(cuò)誤折疊成β片層的前體蛋白,如輕鏈免疫球蛋白,突變的遺傳性甲狀腺素運(yùn)載蛋白,野生型甲狀腺素運(yùn)載蛋白,突變的載脂蛋白,血清淀粉樣A蛋白等,異常聚集在胞外基質(zhì),不斷浸潤(rùn)損傷心肌細(xì)胞,最終導(dǎo)致以進(jìn)行性收縮性和舒張性心力衰竭為主要表現(xiàn)的心臟疾病。由于缺乏特異的臨床表現(xiàn)和敏感的無(wú)創(chuàng)診斷方法,該病的診斷率低,病死率高,預(yù)后差。因此,本研究的目的是總結(jié)近五年在本單位診斷為CA患者的臨床表現(xiàn)、心電圖、超聲心動(dòng)圖、心臟核磁共振成像(cardiacmagnetic resonance imaging,CMR)和放射性核素示蹤技術(shù)等檢查的特點(diǎn),并探討實(shí)驗(yàn)室檢查、心電圖、超聲心動(dòng)圖以及CMR在CA的診斷和評(píng)價(jià)患者預(yù)后的價(jià)值。[研究方法]回顧性分析選取2010年1月至2015年2月在北京協(xié)和醫(yī)院住院期間診斷為CA患者的臨床癥狀體征、實(shí)驗(yàn)室檢查、心電圖、超聲心動(dòng)圖和CMR、放射性核素示蹤檢查和病理組織活檢的結(jié)果,總結(jié)CA的臨床特點(diǎn)。同時(shí)對(duì)患者進(jìn)行電話隨訪,分別探討血清游離輕鏈檢測(cè)、心電圖中假性心肌梗死波形、超聲心動(dòng)圖檢測(cè)的左心房大小和室間隔厚度對(duì)CA患者預(yù)后的影響,同時(shí)通過(guò)系統(tǒng)綜述和meta分析總結(jié)CMR在CA的診斷價(jià)值。[研究結(jié)果]1.研究納入128例CA患者,發(fā)病年齡較晚,平均(55 ± 12)歲,且多見(jiàn)于男性(79例,61.7%)�；颊呷朐喊Y狀各異,以胸悶憋氣(44.5%),下肢水腫(36.7%),氣短(14.1%),乏力(10.9%),腹瀉(9.4%)表現(xiàn)多見(jiàn)。臨床分型中輕鏈型117例(91.4%),其中原發(fā)性系統(tǒng)性淀粉樣變性84例(65.6%),多發(fā)性骨髓瘤伴發(fā)32例(25%),其他輕鏈病相關(guān)1例(0.8%),家族性甲狀腺素運(yùn)載蛋白淀粉樣變3例(2.3%),不明類型8例(6.3%)�；颊咝碾妶D以肢體導(dǎo)聯(lián)低電壓(62例,48.4%)、胸導(dǎo)R波遞增不良(61例,47.7%)、假性心肌梗死波(57例,44.5%)、ST-T改變(98例,76.6%)為主要表現(xiàn)。超聲心動(dòng)圖結(jié)果示左心房前后內(nèi)徑增大,室間隔厚度超過(guò)12mm的患者共有76例(59.4%),44例(34.4%)患者左心室射血分?jǐn)?shù)小于50%,60例(46.9%)患者E/A比值大于2。左室收縮功能減低50例(39.1%),左室限制性舒張功能減低64例(50%)。24例(18.8%)患者超聲心動(dòng)圖出現(xiàn)典型心內(nèi)膜毛玻璃樣改變及顆粒樣強(qiáng)回聲。15例患者進(jìn)行了 CMR檢查,其中14例均有不同程度的延遲強(qiáng)化。6例CA患者接受了 18F-FDG PET/CT檢查,其心肌均未出現(xiàn)放射性攝取增高。2例CA患者進(jìn)行了 99mTc-MIBI腺苷負(fù)荷顯像,其中1例心肌可見(jiàn)放射性缺損及減低區(qū)。21例99mTc-MDP顯像結(jié)果中,2例患者軟組織攝取增加。診斷淀粉樣變性敏感度較高的活檢組織部位為腎臟(100%)、舌體(82.6%)、心臟(80%)和齒齦(71.4%)。2.納入經(jīng)過(guò)血清游離輕鏈檢測(cè)的27例CA患者,研究發(fā)現(xiàn)無(wú)論是采用血清游離輕鏈濃度差還是克隆性免疫球蛋白輕鏈κ、λ比值進(jìn)行分組,高濃度血清游離輕鏈的患者其生存時(shí)間明顯短于低濃度血清游離輕鏈患者。3.研究中36.4%患者心電圖中出現(xiàn)心肌梗死波形,并且假性心肌梗死波形與CA預(yù)后不良相關(guān),伴有假性心肌梗死波患者的生存時(shí)間明顯短于缺如的患者(中位生存時(shí)間 4 months vs.17 months,p0.001)。4.研究發(fā)現(xiàn)左心房增大常見(jiàn)于淀粉樣變性出現(xiàn)心臟受累的患者,特別是出現(xiàn)嚴(yán)重心力衰竭、心功能較差的患者。左心房增大可以評(píng)價(jià)患者預(yù)后,是患者進(jìn)展為嚴(yán)重心力衰竭的危險(xiǎn)因素之一。5.22.4%CA患者不伴有室間隔增厚,但是這部分患者的預(yù)后與伴有室間隔增厚的患者相同。盡管室間隔厚度不能提供整個(gè)隊(duì)列的預(yù)后信息,但是對(duì)于不伴有嚴(yán)重心功能不全的患者來(lái)說(shuō),室間隔厚度增加反而提示患者預(yù)后不良。多因素Cox風(fēng)險(xiǎn)比例模型中,NYHA、E/A比值和假性心肌梗死波可以評(píng)價(jià)預(yù)后。6.通過(guò)系統(tǒng)綜述和meta分析發(fā)現(xiàn)CMR延遲釓強(qiáng)化(late gadolinium enhancement,LGE)的診斷敏感性達(dá)85%,特異性92%。并且LGE可以區(qū)別CA患者和健康對(duì)照(陽(yáng)性似然比為7.481,95%CI:2.835-19.739)。診斷優(yōu)勢(shì)比為71.945(95%CI:23.552-219.77)表明CMR鑒別診斷的準(zhǔn)確度較高。[結(jié)論]臨床上心肌淀粉樣變患者主要以胸悶憋氣、下肢水腫等為臨床表現(xiàn),心電圖示肢體導(dǎo)聯(lián)低電壓、胸導(dǎo)R波遞增不良和假性心肌梗死波,超聲心動(dòng)圖示心室壁增厚伴毛玻璃改變,CMR提示延遲強(qiáng)化。無(wú)創(chuàng)檢查方法,如血清游離輕鏈、心電圖中假性心肌梗死波形和超聲心動(dòng)圖檢測(cè)的左心房大小能夠評(píng)價(jià)患者預(yù)后,同時(shí)CMR診斷心肌淀粉樣變準(zhǔn)確度較高。
[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，

本文編號(hào)：1710134