Heart transplantation in adults with congenital heart disease: experience with 15 patients

End-stage congenital heart disease (CHD) is an important indication for pediatric heart transplantation (HTx) as well as transplantation in adult populations. The purpose of this retrospective analysis was to compare the survival rate of adults who underwent HTx for end-stage CHD with those who underwent HTx for other causes. To find out whether HTx is a viable therapeutic option for adult patients with preoperated CHD, data from 15 adult patients with different forms of CHD, who had previously undergone different corrective and palliative procedures, were retrospectively analyzed and compared with the HTx data of 1400 adult patients (>15 years old) whose indications for HTx were other than end-stage CHD. From 1989 to 2005, 15 adult patients (eight men/seven women) were given transplantation for end-stage CHD. Ten patients had been preoperated once, five patients twice. Their mean age was 34.06 +/- 3.9 years. In five cases, patients had development of acute renal failure. One female patient died 40 days after surgery, after having a cerebral infarction; one male patient died 4 years after HTx for OKT 3 monoclonal antibody-resistant rejection; and two patients died as the result of multiple organ failure at 4 days and 30 days after HTx, respectively; 11 patients are still alive. The cumulative survival rate at 1 year is 80% versus 80% in patients given transplantation for noncongenital indications. Heart transplantation in adults with end-stage CHD can be performed with a good long-term prognosis. Previous palliative operations do not affect outcome after HTx.     

应用Yagel式快速心脏检查法产前筛查先心病的价值研究

目的探讨Yagel式胎儿心脏快速扫描法在胎儿心脏产前诊断中的价值。方法病例选自2002年以来在中国医科大学附属盛京医院、沈阳市妇婴医院、大连妇产医院和锦州市妇婴医院就诊的孕妇7394例,均为单胎妊娠,其中先天性心脏畸形（CHD）高危患者1276例。应用Yagel5个心脏横面检查方法进行胎儿心脏快速检查,并对引产胎儿进行尸体解剖核对产前诊断的正确性;对产前诊断未发现明显异常胎儿进行临床随访,胎儿出生后进行新生儿或婴儿心脏超声检查,判定产前诊断的正确性。结果 1.7394例孕妇中,检查发现胎儿心脏结构异常为79例（1.07%）,其中31例（39.2%）患者来自于CHD高危人群。2.79例产前诊断为CHD患者中,72例选择了终止妊娠放弃胎儿,其中56例进行尸体解剖,其中1例患者病理诊断为永存动脉干畸形,产前诊断为法洛四联症;1例右心室双流出道,产前诊断为大动脉转位;1例为部分型肺静脉异位引流,产前诊断为左心发育不良;1例为主动脉缩窄,产前诊断为左心发育不良。3.79例产前诊断为CHD患者中,7例选择继续妊娠,其中室间隔缺损（VSD）3例,法洛四联症1例,永存动脉干1例,右心室占位病变（0.8cm×0.8cm）1例,轻度肺动脉狭窄伴三尖瓣返流1例。4.6118例产前诊断为正常胎儿心脏患者,新生儿或婴儿心脏超声检查发现室间隔缺损2例（0.03%）;动脉导管未闭2例;房间隔缺损1例;部分肺静脉异位引流1例,主动脉轻度狭窄1例,肺动脉轻度狭窄1例。5.应用Yagel胎儿心脏检查方法诊断胎儿心脏异常的敏感性为90.8%,特异性为100%。结论 1.Yagel式胎儿心脏快速扫描法是产前诊断胎儿心脏畸形的安全、简单和有效方法。2.对所有人群进行胎儿心脏结构产前检查,减少严重心脏病患儿的出生,具有重大的社会和经济意义。     

早期先天性心脏病彩超的筛查

目的及早诊断先天性心脏病（先心病）,降低先心病的发病率及病死率。方法随机选取在大兴妇幼保健院定期检查的孕妇2164例,利用多普勒彩色超声心动图（简称心脏彩超）,常规宫内及生后三天检查,对可疑及确诊先心病定期随访。结果宫内筛查心脏彩超显示复杂先心有19例（此19例胎儿全部被引产）,生后确诊先心病有82例,先心病患病率为4．67％,婴儿期因先心病死亡两例,先心病病死率为2．44％。结论利用心脏彩超进行宫内及早期新生儿心脏检查,并定期随访,可以降低先心病死亡率及病死率。     

Heart transplantation in pediatric patients: twelve-year experience of the Asan Medical Center

Heart transplantation is a standard treatment for end-stage heart disease. Pediatric heart transplantation, however, is not frequently performed due to the shortage of pediatric heart donors. This is the first report of pediatric heart transplantation in Korea. Our retrospective study included 37 patients younger than 18 yr of age who underwent heart transplantation at Asan Medical Center between August 1997 and April 2009. Preoperative diagnosis was either cardiomyopathy (n = 29, 78.3%) or congenital heart disease (n = 8, 22.7%). Mean follow up period was 56.9 ± 44.6 months. There were no early death, but 7 late deaths (7/37, 18.9%) due to rejection after 11, 15, 41 months (n = 3), infection after 5, 8, 10 months (n = 3), suspicious ventricular arrhythmia after 50 months (n = 1). There was no significant risk factor for survival. There were 25 rejections (25/37, 67.6%); less than grade II occurred in 17 patients (17/25, 68%) and more than grade II occurred in 8 patients (8/25, 32%). Actuarial 1, 5, and 10 yr survival was 88.6%, 76.8%, and 76.8%. Our midterm survival of pediatric heart transplantation showed excellent results. We hope this result could be an encouraging message to do more pediatric heart transplantation in Korean society.     

Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi

To examine the role of endogenous proteases in limiting the bronchodilating effects of vasoactive intestinal peptide (VIP) in human airway, we studied precontracted bronchial rings from five nonsmokers undergoing heart-lung transplantation for pulmonary hypertension, either primary or secondary to congenital heart disease. The protease inhibitors aprotinin, leupeptin, phosphoramidon, and soybean trypsin inhibitors significantly potentiated the bronchodilator response to VIP. Even in the presence of the four protease inhibitors, VIP-induced bronchodilation reversed spontaneously in some tissues. These studies show that degradation by endogenous airway proteases is an important determinant of the bronchodilating potency of VIP in isolated human airway.     

Spectrum of congenital heart disease in a tropical environment: an echocardiography study

Echocardiography is a major mode of cardiovascular imaging with versatile applications. Modern two-dimensional echocordiographic techniques provide a comprehensive means for evaluating virtually all forms of congenital heart disease (CHD) found in both adults and children. CHD is an abnormality in cardiocirculatory structure or function that is present at birth, even if it is discovered much later. We set out to describe the spectrum of CHD using echocardiography in two centers in Kano, northern Nigeria. In this retrospective study, transthoracic echocardiography (TTE) data collected from two echocardiography laboratories in Kano over a period of 48 months (June 2002 to May 2006) were reviewed. Patients with diagnosis of congenital heart disease were selected. Information obtained from the records included the age, gender, clinical diagnosis and echocardiographic findings. One-hundred-twenty-two patients had CHD, making 9.3% of the 1312 patients with abnormal echocardiograms. There were 73 males and 49 females (ratio 1.5:1); and their ages ranged from nine days to 35 years. Forty-one (33.6%) children presented for echocardiography before the age of one year, and 69% presented before the age of five years. Thirteen (10.6%) were > or =18 years. Ventricular septal defect (VSD) was the most common echocardiographic diagnosis present in 56 patients (45.9%). Thirty-two (26.2%) had tetralogy of Fallot, and 15 (12.3%) had atrial septal defect (ASD). Ten (8.2%) had endocardial cushion defect, and nine (7.4%) had other congenital heart abnormalities. Coarctation of the aorta and aortic stenosis were rare. CHD is a common cardiovascular problem in our setting, and a number of patients were diagnosed in adulthood. With increasing availability of echocardiographic facilities, more cases of CHD are likely to be identified early.     

Pathologic pulmonary alterations in long-term human heart-lung transplantation

Twenty-one patients with end-stage pulmonary hypertension underwent combined allograft heart-lung transplantation after 1980. Almost 80 per cent of these patients survived beyond the immediate postoperative period, with the longest survival period more than 3 1/2 years at the time of this report. Five patients died in the perioperative or immediate postoperative period, and 11 returned to normal lives with essentially normal pulmonary function. In the remaining five allograft recipients recurrent respiratory infections and progressive obstructive airway disease developed, with superimposed restrictive deficits in three of them. Two open lung biopsies, two autopsies, and one retransplantation were performed in these recipients. Morphologically, these allograft recipients showed extensive bronchiolitis obliterans, interstitial and pleural fibrosis, and accelerated arterial and venous arteriosclerosis. Bronchiolitis obliterans may prove to be a significant complication of heart-lung transplantation.     

Prevalence of human parvovirus B19 DNA in cardiac tissues of patients with congenital heart diseases indicated by nested PCR and in situ hybridization.

BACKGROUND: Infection with parvovirus B19 (B19) was reported to be correlated with myocarditis, cardiomyopathy, and kawasaki disease. But no information is available about the relationship between inutero B19 infection and congenital heart disease (CHD). OBJECTIVE: To explore whether there is relationship between B19 infection and CHD. STUDY DESIGN: Retrospective investigation of biopsy samples from CHD patients from January 1996 to December 1998. METHODS: Parvovirus B19 was detected in biopsy samples from 42 cases of CHD patients and 38 cases of biopsy or autopsy samples from patients with other diseases (controls) by nested polymerase chain reaction (PCR) and in situ hybridization (ISH) technique. HE staining was also performed to observe the morphology of these cardiac tissue samples. RESULTS: Nested PCR assay indicated that seven of 42 (16.7%) CHD cardiac tissue were B19 DNA positive, while all the 38 controls were B19 DNA negative, the difference is significant (P = 0.012). ISH assay indicated that five of 42 (11.7%) CHD cardiac tissues were positive for B19 DNA and none of the control cardiac tissue were positive, all B19 DNA positive signals were located in the nucleuses of cardiac cells. HE staining showed that there was no inflammatory change in B19 DNA positive cardiac tissue. CONCLUSIONS: Parvovirus B19 DNA was presented in part of CHD cardiac tissues and located in nucleus, which suggested that inutero B19 infection might be correlated with CHD.     

多重连接依赖的探针扩增技术在检测胎儿先天性心脏病遗传学病因中的应用

目的探讨多重连接依赖的探针扩增技术（MLPA）用于检测胎儿先天性心脏病遗传学病因的可行性。方法 2006年11月至2009年12月间,共收集34例超声发现为先天性心脏病胎儿的脐血进行染色体核型分析,同时提取脐血淋巴细胞DNA后进行MLPA检测。选取先前已进行核型分析及MLPA确诊的32例标本作为对照,其中包括13-三体、16-三体、18-三体、21-三体、21-三体合并22q11微扩增以及不同范围的22q11微扩增或微缺失。结果 66例标本中,本实验所用的MLPA探针共检出3例13-三体、7例18-三体、10例21-三体、1例21-三体合并22q11微扩增。5例22q11微缺失的缺失范围与已知结果吻合。在34例新收集标本的检测中,提示2例为22q11微缺失（3Mb）,随后通过ML-PA-P250探针组进行检测得到进一步验证。所有标本中有5例16-三体、1例三倍体（69,XXX）以及一例平衡易位未被MLPA检出。结论 MLPA-P290可用于检测可导致先天性心脏病的常见非整倍体及微缺失、微扩增异常,且具有高效、价廉等优点,有较好的临床应用价值。     

Molecular mechanisms of congenital heart disease

BackgroundCongenital heart disease (CHD) is the most common type of birth defect. Despite the many advances in our understanding of cardiac development and many genes related to cardiac development identified, the fundamental etiology for the majority of cases of congenital heart disease remains unknown.MethodsThis review summarizes normal cardiac development, outlines the recent discoveries of the genetic causes of CHD, and provides possible strategies for exploring them.ResultsCHD is a multifactorial complex disease, with environmental and genetic factors playing important roles. A number of causative genes of selected congenital heart defects and genetic syndromes have been found. The molecular mechanisms of CHD may include mutations in components of the cardiac gene network, altered haemodynamics, regulatory pathway of cardiac genes, micro-RNA dysfunction, epigenetics, adult congenital heart diseases, and so on.ConclusionsThe molecular basis of CHD is an exciting and rapidly evolving field. The continuing advances in the understanding of the molecular mechanisms of CHD will hopefully result in improved genetic counseling and care of affected individuals and their families.     

重症婴儿先天性心脏病手术的体外循环策略

目的探讨重症婴儿先天性心脏病外科治疗的体外循环策略。方法回顾性分析接受心内直视手术治疗的354例重症先心病婴儿的临床资料。术前合并有心血管系统、呼吸系统、消化系统等严重并发症患儿318例（89.8%）。根据不同手术方式,术中采用浅度低温（80例,22.6%）、中度低温（191例,54.0%）和深低温低流量灌注（79例,22.3%）以及深低温停循环（4例,1.1%）的体外循环方法;心肌保护措施采用不阻断主动脉心脏不停跳（80例）或阻断主动脉根部间断灌注4∶1冷血停搏液（274例）;复温后行平行超滤与改良超滤联合应用。结果心脏停跳体外循环时间为（112.11±31.37）min,阻断主动脉时间（56.12±22.17）min;心脏不停跳体外循环时间为（79.3±19.1）min,阻断腔静脉时间（39.1±11.8）min;4例采用深低温停循环体外循环下行心内畸形矫治术,体外循环时间为114～161 min,阻断主动脉时间56～116 min,停循环5～16 min。253例开放主动脉后自动复跳,自动复跳率为92.3%（253/274）,全组8例停机困难,术后死亡11例,死亡率为3.1%。结论针对具体患儿制定合理的预充预案、选择高质量的体外循环管道和氧合器,术中选择合理的体外循环方案、常规进行超滤和加强重要脏器保护是重症婴儿先天性心脏病外科治疗成功的保障。     

接受体外循环的先心病患儿认知功能的动态研究

目的: 研究0～4岁行体外循环(Cardiopulmonary bypass,CPB)心脏直视手术的先天性心脏病(Congenital heart disease,CHD)患儿,在术前、术后1周、术后1月神经认知功能的情况.方法: 对110例0～4岁CPB下行心脏直视手术的患儿(紫绀型36例,非紫绀型74例),在术前、术后1周、1月用Gesell发展量表进行神经认知功能测评.结果: 患儿术前神经认知功能处于中下水平,紫绀型患儿的应物能、应人能、运动能、语言能得分均低于非紫绀型患儿[(81.5 ±7.0)vs.(87.7 ±7.3)、(80.7 ±6.8)vs(87.7±8.1)、(79.2±6.4)vs.(87.2 ±8.7)、(80.8±6.1)vs(87.4 ±8.6),P＜0.001或0.01];4个方面得分术后1周均低于术前[如应人能:(82.8 ±7.7)vB.(85.4±8.3),P=0.002],术后1月均高于术前[如应人能:(91.3 ±6.2)vs.(85.4±8.3),P=0.001];年龄与应物能、应人能、运动能、语言能均呈负相关(如术后1周年龄与非紫绀型应人能B=-3.7,与紫绀型应人能β=-0.6);非紫绀型组的ICU停留时间与术后1周应人能、运动及术后1月应人能呈负相关(13=-0.6、-0.4、-0.4);非紫绀型组与紫绀型组的最低鼻咽温与术后1周语言能呈正相关(β=1.7、2.7);紫绀型组主动脉阻断时间与术后1周认知能力的4个方面及术后1月应物、应人呈负相关(β=-9.6、-3.9、-3.4、-4.7、-3.9、-7.8).结论: 接受手术时的年龄越大认知功能水平越低;在短期内,ICU停留时间、最低鼻咽温、主动脉阻断时间对患儿的认知功能有影响,且对紫绀型患儿的影响大于非紫绀型患儿.     

先天性心脏病心肌活检组织中微小病毒感染的定位

目的 了解人微小病毒Ｂ１９（Ｐａｖｏｖｉｎｕｓ Ｂ１９）感染在先天性心脏病（Ｃｏｎｇｅｎｔｉａｌ ｈｅａｒｔ ｄｉｓｅａｓｅ，ＣＨＤ）心脏组织中的定位。方法 采用巢式聚合酶链反应（ＰＣＲ）和组织原位杂交（ＩＳＨ）技术，对３７例ＣＨＤ患者外周血及手术活检的心肌组织和２８例非先天畸形心肌组织进行Ｂ１９ ＤＮＡ的检测，结果 ３７例ＣＨＤ组中Ｂ１９ ＤＮＡ在血清及心肌组织中阳性率分别为１６．２２％（６／３     

产前超声诊断先天性心脏病合并心外畸形的应用及对优生优育的指导价值

目的探讨产前超声诊断应用于先天心脏病合并心外畸形的临床价值及对优生优育的指导价值。方法选取2017年5月~2018年5月于我院接受产前超声诊断结果异常的132例孕妇作为主要研究对象,所有孕妇均接受产前超声诊断,并产后随访6个月,分析其CHD及合并心外畸形的类型,以及产前超声诊断的临床价值。结果132例参与研究的孕妇中,随访成功108例,随访率为81.82%。随访成功的108例孕妇中,共检出24例CHD胎儿,产前超声诊断检出21例,诊断准确率为87.50%,漏诊率为12.50%。19例仅引产后尸体解剖检查证实为CHD,5例经出生后超声复查证实为CHD。24例CHD胎儿中,单纯先天性心脏病13例,其中4例完全性大动脉移位、3例左心发育不良、1例法洛四联症、5例完全性心内膜垫缺损,合并心外畸形11例,其中1例三尖瓣下移畸形合并肾积水,肺囊腺癌、7例室间隔缺损合并肾积水,内腔反位,脐膨出、1例法洛四联症合并羊水少,脊柱侧弯、1例永存左上腔静脉合并肾积水、1例右室双出口合并马蹄内翻足。对11例CHD合并心外畸形的胎儿进行随访,其中10例选择引产,1例室间隔缺损合并肾积水,内腔反位,脐膨出的孕妇选择继续妊娠,产后随访妊娠结果与产前超声诊断结果基本相同。结论产前超声诊断应用于先天性心脏病合并心外畸形胎儿的临床价值较高,且对优生优育具有一定的指导作用。     

An investigation of the optimal inter-pregnancy interval following pregnancy with a fetus with congenital heart disease

IntroductionCongenital heart defects (CHD) are one of the most commonly diagnosed congenital malformations in fetuses and newborns. The aim of the study was to determine whether inter-pregnancy interval (IPI), maternal age or number of pregnancies had any influence on the recurrence of congenital heart disease in subsequent pregnancies.Material and methodsWe found in our database 144 women with subsequent pregnancies after CHD in a previous pregnancy. Each woman was selected according to the eligibility and exclusion criteria. Medical history as well as obstetrics history were recorded. Comparisons of groups with and without a recurrence of CHD were performed. We calculated hazard ratios for recurrence of CHD. We also performed analysis of the impact of confounding variables: maternal age and parity. Missing data were excluded from the analysis. Smoking habits as well as socio-demographic characteristics were not evaluated in this study.ResultsA higher risk of recurrence of CHD correlated with a shorter IPI, with a median of 11 months compared with 24 months for the group of healthy fetuses in subsequent pregnancy. The results were statistically significant. Parity was proven to be an important confounder of the study. Multivariable analysis including parity and maternal age did not affect the confidence intervals of hazard ratios for IPI.ConclusionsThe optimal IPI to reduce the risk of recurrence of CHD is 24 months. Shorter intervals are related to a higher risk of recurrence of CHD in the next pregnancy and are independent on the age of the woman and parity.     

同种异体带瓣管道在小儿复杂先天性心脏病中的应用

目的 探讨同种异体带瓣管(VHC)在复杂先天性心脏病（先心病）中的临床应用价值。方法 1993年－2000年共应用VHC重建右心室流了道治疗各种复杂先心病9年。VHC均采用同种异体带瓣主动脉；术后常规监测心肺功能，呼吸机辅助呼吸，应用正性肌力药物和血管扩张剂等辅助心功能。结果 8例成活，1例死亡，死亡率11．1％，死亡原因急性右心衰竭，合并纵隔感染2例，经清创引流治愈。随访3－6年，患儿生长发育良好，能正常上学；无远期死亡。结论 VHC对某些复杂先心病有广泛的应用前景。     

产前超声诊断胎儿先天性心脏病中染色体核型异常的分析

目的调查分析产前超声筛查后确诊先天性心脏病胎儿中染色体异常的分布,探讨先天性心脏病的病因,提高产前诊断率。方法对2011年1月至2013年6月在本院产前诊断中心产科门诊B超诊断的先天性心脏病胎儿进行羊水或脐带血的染色体核型检查,并综合分析先天性心脏病畸形分类和染色体异常的关系。结果确诊的70例先天性心脏病病例中,伴染色体异常者18例,占25.71%（18/70）,其中21-三体7例,18-三体7例,13-三体2例,X单体2例。先天性心脏病合并心外畸形的胎儿22例,其中有14例（63.64%）染色体检查发现异常,仅有先天性心脏病的胎儿核型分析发现4例染色体异常,占单纯先天性心脏病的8.33%（4/48）。CHD胎儿中,100%的13-三体、85.71%的18-三体、71.43%的21-三体和50%的X单体均不同程度的伴有心外器官的畸形。结论染色体异常是产前B超诊断的先天性心脏病,尤其是复杂型先天性心脏病或有合并其他心外畸形的主要病因。对于B超筛查出的复杂型先天性心脏病或有合并其他心外畸形的胎儿,应重视其染色体的检查。     

Heart failure in congenital heart disease: the role of genes and hemodynamics

Heart failure can be a consequence of insufficient palliation of structural malformations in patients with congenital heart disease (CHD) or genetic perturbations resulting in cardiomyopathies. Although CHD is traditionally considered a pediatric clinical problem, there is a rapidly increasing population of patients surviving into adulthood with CHD and a corresponding increase in the rate of hospital admissions for adult CHD patients with heart failure. Therefore, there is recognition of the clinical importance in translating conventional heart failure pharmacotherapies to patients with CHD, improving management of heart failure in the context of structural consequences of CHD, and understanding the underlying genetic abnormalities which impact myocardial performance. Heart failure in CHD typically involves complex interactions between primary structural defects, the consequences of interventions (i.e., residual lesions), and the heart’s response to enhanced myocardial mechanical stress which depends on many other genetic factors (i.e., gene modifiers). In this review, we will examine how altered genes and hemodynamic loading contribute to heart failure seen in congenital heart patients. Understanding mechanisms of myocardial response and remodeling within the congenital population can provide insight into physiological principles and improve our understanding of heart failure.