本文選題：心肌致密化不全 + 先天性心臟病　； 參考：《山東大學(xué)》2014年博士論文

【摘要】：背景 心肌致密化不全(Noncompaction of the ventricular myocardium, NVM)是一種罕見(jiàn)的特殊類(lèi)型的先天性心室肌發(fā)育不全性心肌病,目前病因尚不明確,病變主要累及心臟左心室或(和)右心室,主要特征為左心室或(和)右心室腔內(nèi)存在大量粗大突起的肌小梁及深陷隱窩,可合并其他心臟畸形(congenital heart disease, CHD),并導(dǎo)致一系列相關(guān)的臨床癥狀,其癥狀主要為心功能不全、心律失常和各系統(tǒng)栓塞,但其癥狀的首發(fā)年齡差別很大,而且臨床表現(xiàn)各異,預(yù)后差別也較大。到目前為止,國(guó)內(nèi)外僅有少量文獻(xiàn)報(bào)道,且各方面報(bào)道結(jié)果差異較大。 隨著人們對(duì)本病認(rèn)識(shí)的加深和成像技術(shù)的不斷提高,近年來(lái)越來(lái)越多的心肌致密化不全被報(bào)道,文獻(xiàn)主要以個(gè)案報(bào)道為主,少數(shù)病例報(bào)道病例數(shù)在10例-50例之間,50例以上的病例報(bào)道也不過(guò)2-3篇。再加上心肌致密化不全分型復(fù)雜也較為模糊,又使得較大樣本報(bào)道的有效性大大降低,報(bào)道從臨床癥狀、心電圖異常率、栓塞發(fā)生率到死亡率等等差別比較大,譬如死亡率從2%到60%不等,這對(duì)于本病的認(rèn)識(shí)造成非常的不利影響。心肌致密化不全合并先天性心臟發(fā)生率可達(dá)78%,越來(lái)越多的心肌致密化不全合并先天性心臟病患者被發(fā)現(xiàn),其手術(shù)治療和介入治療方法的療效觀察尚不多見(jiàn),主要是個(gè)案報(bào)道。盡管人們對(duì)心肌致密化不全的研究付出了很大的努力,但是目前病因尚不明確,發(fā)病機(jī)制也不是很清楚,治療方法多是對(duì)癥治療和心臟移植。解決以上問(wèn)題,將會(huì)使人們對(duì)本病的認(rèn)識(shí)向前大大推進(jìn)。研究目的 由于心肌致密化不全尚存在以上問(wèn)題,本研究的研究目的就是通過(guò)研究大型心臟中心的病歷資料并對(duì)其進(jìn)行相關(guān)分析,解決以上問(wèn)題。1、明確心肌致密化不全的臨床特點(diǎn)及各分型的特點(diǎn),包括發(fā)病率、癥狀、體征、心電圖、心臟彩超、治療及預(yù)后情況,找出心肌致密化不全不良預(yù)后的危險(xiǎn)因素。2、報(bào)道心肌致密化不全合并先天性心臟病的外科手術(shù)治療和介入治療的效果,明確手術(shù)治療和介入治療是否有效。3、研究心肌致密化不全的發(fā)病機(jī)制和探討治療方法。研究方法 收集2009年4月至2011年10月間山東省立醫(yī)院0-18歲的所有診斷心肌致密化不全的患者的病歷資料,包括住院電子病歷資料、門(mén)診電子病歷資料、隨訪(fǎng)資料,超聲數(shù)據(jù)庫(kù)。 收集內(nèi)容并登記,一般資料：姓名、性別、年齡、診斷、心功能分級(jí),癥狀、體征、治療方法、治療效果等；治療方法包括藥物治療、介入治療和手術(shù)治療。癥狀包括胸悶、憋氣、心慌等；體征包括心臟雜音、呼吸困難、水腫、發(fā)育遲緩、特殊面容等。胸片資料：計(jì)算心胸比率。記錄心電圖和24小時(shí)心電圖資料。心臟彩超資料：左室舒張末內(nèi)徑,心功能指數(shù),縮短分?jǐn)?shù),心肌致密化不全累及部位,合并其他心臟畸形及超聲繼發(fā)改變等情況。隨訪(fǎng)資料：所有病人在首次就診3、6、12月后門(mén)診進(jìn)行隨訪(fǎng),其后每年進(jìn)行隨訪(fǎng)。隨訪(fǎng)內(nèi)容包括：癥狀、體征、病史,體格檢查、心功能分級(jí),胸片、心臟彩超、心電圖和24小時(shí)心電圖。隨訪(fǎng)至2012年4月31日,完成率100%。所有資料收集后錄入Excel表,然后在SPSS16.0建庫(kù)進(jìn)行統(tǒng)計(jì)學(xué)分析。 解決以上三個(gè)問(wèn)題需對(duì)以下6個(gè)方面進(jìn)行研究。1、通過(guò)描述的方法描述全部患兒的整體特征和各個(gè)部分的特征描述,包括：一般性描述、合并先心病特征、心電圖特征、致密化不全分布特點(diǎn)。通過(guò)與其他小兒心肌致密化不全的研究進(jìn)行比較,明確本研究的有效性；通過(guò)與其他成人心肌致密化不全的研究比較,找出小兒心肌致密化不全與成人心肌致密化不全的區(qū)別,結(jié)果采用Fisher's精確檢驗(yàn)或χ2檢驗(yàn)。對(duì)本組合并先心病和孤立性心肌致密化不全進(jìn)行比較,判斷兩種情況的差別,采用Pearson chi-square法或者Fisher's精確檢驗(yàn)。2、相關(guān)死亡和(或)反復(fù)心衰的危險(xiǎn)因素分析,采用Kaplan-Meier曲線(xiàn)及Log Rank檢驗(yàn)。包括以下幾個(gè)方面的檢驗(yàn)：致密化不全累及部位數(shù)量、性別、年齡(1歲)、有無(wú)癥狀、有無(wú)嚴(yán)重心律失常、EF(50%)。3各治療組治療效果的觀察,包括手術(shù)組治療效果觀察(手術(shù)方法及病人特征、心臟彩超結(jié)果、心電圖發(fā)現(xiàn)、胸部x-線(xiàn)發(fā)現(xiàn)、臨床數(shù)據(jù)、手術(shù)結(jié)果、術(shù)后早期結(jié)果、術(shù)后6月結(jié)果、術(shù)后遠(yuǎn)期結(jié)果、手術(shù)組危險(xiǎn)因素篩選),介入組治療結(jié)果(病人特征、術(shù)后6月患兒的EF,CTR和NYHA分級(jí)),孤立性NVM的藥物治療加心律治療結(jié)果。4三個(gè)治療組免除死亡和反復(fù)心衰的生存情況。5手術(shù)效果進(jìn)一步評(píng)價(jià)。6合并先天性心臟病與致密化不全部位的關(guān)系。使用SPSS16.0進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差表示,分類(lèi)變量使用計(jì)數(shù)和百分比表示,全部47例患者危險(xiǎn)因素分析采用Kaplan-Meier曲線(xiàn)配合Log Rank檢驗(yàn)逐個(gè)因素檢驗(yàn)進(jìn)行直觀表達(dá),部分變量采用單因素分析。時(shí)間和時(shí)間相關(guān)事件使用圖標(biāo)和Kaplan-Meier曲線(xiàn)表示,在首診6個(gè)月時(shí)心功能指數(shù)、心胸比率、心功能分級(jí)結(jié)果采用t檢驗(yàn),分析挑選出來(lái)的危險(xiǎn)因素使用Fisher's精確檢驗(yàn),與其他組進(jìn)行比較使用Fisher's精確檢驗(yàn)或胞檢驗(yàn)。P值0.05為有統(tǒng)計(jì)學(xué)意義。 [結(jié)果] 結(jié)果1：2009年4月至2011年10月,確診NVM患兒47例,占同期超聲心動(dòng)圖檢查患兒的0.17%,占心肌病的12.2%,占先天性心臟病的1.1%。診斷時(shí)年齡3.88±3.76歲(1月-12歲),小于1歲19例,占總病例的40.43%,合并其他先天性心臟畸形37例,占NVM的78.72%,孤立性NVM10例,男性略多于女性55.3%：44.7%；《1LV：BV：RV比例為34：9：4(72.3%：19.1%：8.6%)：所有患者平均LVEF為58.94%(20%-78%)其中LVEF500%34例,占72.34%,LVEF≤50%者13例,占27.66%；心胸比率大于55%占76.6%：其中心臟重度擴(kuò)大17例,占36.2%。心電圖異常38例,占80.9%；合并嚴(yán)重心律失常10例,占21.3%；有自覺(jué)癥狀病例24例,占51.1%,23例無(wú)癥狀,占總數(shù)的48.9%。特殊面容2例,無(wú)嚴(yán)重栓塞病史,病歷未記載家族特性。外科手術(shù)治療16例,介入治療18例,藥物治療13例。隨訪(fǎng)1.83±0.90年,恢復(fù)良好30例(62.5%),心衰復(fù)發(fā)4例(8.3%),反復(fù)心衰5例(10.4%),死亡8例(16.7%)。心肌致密化不全幾乎可合并所有類(lèi)型先天性心臟病動(dòng)脈,導(dǎo)管未閉和室間隔缺損是最常見(jiàn)的心臟畸形,發(fā)生率分別為59.4%和27%。心電圖異常發(fā)生率80.9%,主要為ST-T改變,異常Q波；嚴(yán)重心律失常發(fā)生率為21.3%。 心肌致密化不全最常見(jiàn)發(fā)生部位為左室尖,發(fā)生率為76.6%,其他部位依次為左室中段后壁48.9%,左室中段側(cè)壁34.0%,室間隔中段25.5%,右室尖23.4%,右室側(cè)壁6.4%。與其他小兒NVM研究的比較結(jié)果顯示：小兒心肌致密化不全臨床特征相對(duì)穩(wěn)定；與成人NVM在心電圖改變方面存在差異。本組合并先心病和孤立性NVM在多個(gè)方面存在差異,可能與樣本選擇有關(guān)。結(jié)果2：心肌致密化不全累及范圍(P0.01)、EF(P0.01)、合并嚴(yán)種心律失常(P=0.038)、有臨床癥狀(P0.01)是死亡和反復(fù)心衰的危險(xiǎn)因素,年齡(P=0.27)、性別(P=0.94)不是。 結(jié)果3：手術(shù)組：手術(shù)死亡2(12.5%)例,術(shù)后6月,EF沒(méi)有明顯改善(61.77±12.29%vs64.85±6.07%,P=0.207),但是NYHA心功能分級(jí)改善明顯(2.38±0.89vs1.62±0.65,P=0.009),心胸比率顯示心臟有縮小(P0.001)。EF50%為手術(shù)組危險(xiǎn)因素(P=0.018)。介入組患兒病情輕,效果良好,無(wú)遠(yuǎn)期死亡,隨訪(fǎng)效果良好。孤立性NVM藥物治療組病情重,NVM累及范圍較廣,平均累及2.7個(gè)部位；合并較嚴(yán)重心律失常5例,EF較低,為44.2±14.6%,7(70%)例小于50%；心臟擴(kuò)大明顯,CTR為0.67±0.05,7例≥0.65,70%重度心臟擴(kuò)大。死亡4例,反復(fù)心衰心功能持續(xù)下降2例,心功能無(wú)惡化或改善4例。結(jié)果4：三組生存曲線(xiàn)存在差別。與樣本選擇有關(guān)。結(jié)果5：對(duì)手術(shù)效果進(jìn)一步評(píng)價(jià)發(fā)現(xiàn),手術(shù)能夠有效免除有癥狀的NVM合并先心病的死亡和反復(fù)心衰的發(fā)生率(P=0.037)。結(jié)果6：致密化不全發(fā)生部位與先天性心臟病發(fā)生部位存在關(guān)系。 結(jié)論 小兒心肌致密化不全臨床特征相對(duì)穩(wěn)定,以往報(bào)道差異與樣本選擇有關(guān),小兒心肌致密化不全與成人心肌致密化不全在心電方面存在差異。心肌致密化不全累及范圍、EF50%、合并嚴(yán)種心律失常、有臨床癥狀是死亡和反復(fù)心衰的危險(xiǎn)因素。手術(shù)和介入治療可有效改善預(yù)后,心律失常的治療也可改善預(yù)后。心臟微循環(huán)障礙可能是發(fā)病基礎(chǔ),致密化不全發(fā)生部位與先天性心臟病發(fā)生部位存在關(guān)系。心肌致密化不全的研究還需要各方面進(jìn)一步研究進(jìn)行統(tǒng)一、達(dá)成共識(shí)。
[Abstract]:background
Noncompaction of the ventricular myocardium (NVM) is a rare and special type of congenital cardiomyopathy with congenital ventricular myogenesis. The cause of the disease is not yet clear, and the lesions mainly involve the left ventricle or (and) right ventricle of the heart, mainly characterized by a large number of large projections in the left ventricle or (and) right ventricle. Muscle trabeculae and deep recess can merge with other cardiac malformations (congenital heart disease, CHD) and cause a series of related clinical symptoms. The symptoms are mainly cardiac insufficiency, arrhythmia and systemic embolism. However, the initial age of the symptoms varies greatly, and the clinical manifestations are different and the prognosis is different. So far, domestic There are only a few reports outside, and the results are quite different from each other.
With the deepening of people's understanding of this disease and the continuous improvement of imaging technology, more and more myocardial densification has been reported in recent years. The main cases are reported mainly by case reports. The number of cases reported in a few cases is between 10 cases of -50 cases, and more than 50 cases reported in more than 2-3 cases. Vagueness, which makes the effectiveness of large sample reports greatly reduced, and reports from clinical symptoms, abnormal rates of electrocardiogram, the incidence of embolism to mortality, and so on, such as mortality from 2% to 60%, which has a very negative impact on the understanding of the disease. The more patients with myocardial densification and congenital heart disease have been found, the effect of surgical treatment and interventional therapy is not much observed, mainly in case reports. Although great efforts have been made in the study of myocardial densification, the etiology is not clear and the pathogenesis is not very clear, treatment is not very clear. Most of these methods are symptomatic treatment and heart transplantation. To solve these problems, we will make people's understanding of this disease advance greatly.
Because of the problems of myocardial densification, the purpose of this study is to study the medical records of large cardiac centers and to analyze them, to solve the above problem.1, to clarify the clinical characteristics and the characteristics of various types of myocardial densification, including the incidence, symptoms, signs, electrocardiogram, cardiac color Doppler, treatment and treatment. To find out the risk factors for the prognosis of myocardial densification,.2, the effect of surgical and interventional therapy on myocardial densification and congenital heart disease is reported. It is clear whether surgical treatment and interventional therapy are effective.3, study the pathogenesis of myocardial densification and study the method of treatment.
The medical records of all patients with myocardial densification at the age of 0-18 in Shangdong Province-owned Hospital from April 2009 to October 2011 were collected, including in-patient electronic medical records, outpatient medical records, follow-up data, and ultrasonic databases.
Collection of contents and registration, general information: name, sex, age, diagnosis, classification of heart function, symptoms, signs, treatment, treatment effect and so on; the treatment includes drug treatment, interventional therapy and surgical treatment. Symptoms include chest distress, suffocation, and palpitation. Symptoms include heart murmur, dyspnea, dropsy, retardation, special facial features, etc. Chest data: computed cardiothoracic ratio, record ECG and 24 hour electrocardiogram data. Cardiac color Doppler data: left ventricular end diastolic diameter, cardiac function index, shortening score, myocardial densification involvement, other cardiac malformation and secondary ultrasound changes. Follow-up information: all patients were in the outpatient for the first time after 3,6,12 months. Follow up, followed up every year, followed up each year, including symptoms, signs, medical history, physical examination, heart function classification, chest film, heart color Doppler, electrocardiogram and 24 hour electrocardiogram. Follow up to April 31, 2012, complete rate of 100%. data collection, Excel form, and then statistical analysis in SPSS16.0 database.
To solve the above three problems, we need to study the following 6 aspects:.1, describing the overall characteristics and the characteristics of all the parts of the children, including the general description, the characteristics of the congenital heart disease, the characteristics of electrocardiogram, and the densification of the children. Comparing with the study of other adult myocardial densification, the difference between the densification of the myocardium in children and the densification of the adult myocardium was compared with that of the adult myocardial densification. The results were compared with the Fisher's test or the chi 2 test. Two cases were judged by the comparison of the combination of congenital heart disease and the densification of isolated cardiac muscle. The difference, using Pearson chi-square or Fisher's accurate test of.2, analysis of risk factors for related death and / or recurrent heart failure, using Kaplan-Meier curve and Log Rank test, including the following tests: densification not involved in the number of parts, sex, age (1 years), symptoms, severe arrhythmia, EF (50%).3 The observation of the therapeutic effect of the treatment group included the observation of the therapeutic effect of the operation group (surgical method and patient characteristics, cardiac color Doppler results, electrocardiogram discovery, chest x- line discovery, clinical data, surgical results, early postoperative results, June results after operation, postoperative long-term results, screening of risk factors in hand group), intervention group treatment results (patient characteristics, operation) The EF, CTR and NYHA classification of children in June, the drug treatment of isolated NVM and the result of cardiac arrhythmia,.4 three treatment groups were relieved of death and the survival of repeated heart failure. The effect of.5 operation was further evaluated in the relationship between.6 combined with congenital heart disease and densification area. Statistical analysis was performed with SPSS16.0, and the measurement data used mean standard deviation. The classification variables were expressed by counting and percentage. The analysis of risk factors in all 47 patients was expressed by Kaplan-Meier curve and Log Rank test by one by one factor test. Some variables were analyzed by single factor analysis. The time and time related events were represented by icons and Kaplan-Meier curves, and the heart function was indicated at the first 6 months of first visit. Number, cardiothoracic ratio, and cardiac function classification results were t test, and the selected risk factors were analyzed by Fisher's accurate test. Compared with other groups, Fisher's accurate test or cell test.P value 0.05 were statistically significant.
[results]
Results from April to October 2011 1:2009, 47 children were diagnosed with NVM, accounting for 0.17% of children with echocardiography, accounting for 12.2% of cardiomyopathy, accounting for 3.88 + 3.76 years of age (January -12 years) for congenital heart disease (-12 years in January), 19 cases younger than 1 years old, accounting for 40.43% of the total cases, 37 cases of other congenital heart malformations, 78.72% of NVM, isolated NVM In 10 cases, the male was slightly more than the female 55.3%:44.7%; the proportion of <1LV:BV:RV was 34:9:4 (72.3%:19.1%:8.6%). The average LVEF of all patients was 58.94% (20%-78%) in LVEF500%34 cases, 72.34%, LVEF < 50%, 13, 27.66%, and the heart rate greater than 55%, 76.6%: 38 cases of severe cardiac enlargement, accounting for 38 cases of 36.2%. ECG, 80. .9%, 10 cases with severe arrhythmia, accounted for 21.3%, 24 cases of conscious symptoms, 51.1%, 23 asymptomatic, 2 cases of 48.9%. special face, no history of severe embolism, no family history, 16 cases of surgical treatment, 18 cases of interventional therapy, 13 cases, 1.83 + 0.90 years, recovery of 30 cases (62.5%), heart failure recovery. 4 cases (8.3%), 5 cases of recurrent heart failure (10.4%), 8 cases of death (16.7%). Myocardial densification was almost combined with all types of congenital heart disease. The most common cardiac malformation was ductus arteriosus and ventricular septal defect, the incidence rate was 59.4% and 27%. electrocardiogram was 80.9%, mainly ST-T change, abnormal Q wave, and serious arrhythmia. The incidence is 21.3%.
The most common site of myocardial densification was left ventricular apex, the incidence was 76.6%, the other parts were 48.9% in the posterior wall of the left ventricle, 34% in the middle of the left ventricle, 25.5% in the middle of the ventricular septum, 23.4% in the right ventricular apex, and the comparison between the right ventricular wall 6.4%. and other children NVM showed that the clinical characteristics of the densification of the myocardium were relatively stable in children. There are differences in electrocardiogram changes with adult NVM. There are many differences between this combination, congenital heart disease and isolated NVM, which may be related to the selection of samples. Results 2: myocardial densification is not involved in the range (P0.01), EF (P0.01), combined severe arrhythmia (P=0.038), and the clinical symptoms (P0.01) are the risk factors of death and repeated heart failure. Age (P=0.27), sex (P=0.94) is not.
Results 3: operation group: Operation death 2 (12.5%) cases, after June, EF did not improve (61.77 + 12.29%vs64.85 + 6.07%, P=0.207), but NYHA cardiac function classification improved significantly (2.38 + 0.89vs1.62 + 0.65, P=0.009), cardiac ratio showed that the heart had reduced (P0.001).EF50% as the risk factor of operation group (P=0.018). Good, no long-term death, good follow-up effect. The patients in the isolated NVM treatment group were seriously ill, NVM was involved in a wide range, with an average of 2.7 parts; 5 cases with severe arrhythmia, 44.2 + 14.6%, 7 (70%) less than 50%; the heart enlargement was obvious, CTR was 0.67 + 0.05,7 cases more than 0.65,70% severe heart enlargement. 4 cases died of repeated heart failure. The cardiac function continued to decline in 2 cases, with no deterioration of cardiac function or improvement in 4 cases. Results 4: the survival curve of the three groups was different. The results were related to the selection of samples. Result 5: further evaluation of the effect of the operation showed that the operation could effectively relieve the symptoms of NVM combined with congenital heart disease and the incidence of repeated heart failure (P=0.037). Results 6: densification Location is associated with the site of congenital heart disease.
conclusion
The clinical characteristics of myocardial densification in children are relatively stable. The difference in the previous reports is related to the selection of samples. There is a difference in cardiac densification in children with adult myocardial densification in the field of electrocardiography. Myocardial densification is not involved in the range of myocardial densification, EF50%, combined with severe arrhythmia, and the clinical symptoms are the risk factors of death and repeated heart failure. Surgical and interventional therapy can improve the prognosis effectively, and the treatment of arrhythmia can also improve the prognosis. Cardiac microcirculation may be the basis of the disease. The site of the densification is related to the site of congenital heart disease. The study of myocardial densification need to be unified in all aspects and reach a consensus.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R725.4

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