Fine Structure of A: Autonomic Nerve Fibers and Terminals in Human Myocardium; and B: Myocardial Changes in Congenital Heart Disease

In a histological and fine structural study of right atrial biopsy specimens from 31 patients with rheumatic heart disease (RHD), aged 7 to 46 years, and 11 patients with congenital heart disease (CHD), aged 3 to 36 years, nerve fibers or endings were seen by electron microscopy in 11 specimens. There was concurrence of ordinary axons along with terminals bearing pale cholinergic or dark adrenergic synaptic vesicles. Smaller and denser cholinergic vesicles suggested proliferation followed by exhaustion of such nerve endings. The closest proximity of nerve terminal to muscle fiber was about 100 nm. In one RHD specimen a “specific terminal cell” was present between a nerve ending and muscle fiber; in another a possible neuromuscular contact was developing at the surface of a regenerating small muscle fiber with a few myofilaments. Unmyelinated axons amidst increased subendocardial and subepicardial collagen, with prominent fibroblasts and depleted muscle fibers, were seen more frequently in specimens of CHD. Loss of myofibrils and accumulation of mitochondria, with infrequent formation of lipofuscin bodies, characterized degenerating muscle fibers in CHD also, although to a lesser degree than in RHD (reported earlier, 1985). The myocardial blood vessels in CHD tended to have pale swollen endothelial cells and narrowed lumen. The most severely affected cases of CHD were those with (1) a very wide atrial septal defect (ASD), (2) ventricular septal defect (VSD) with vegetations near the defect, (3) 1 infundibular pulmonary stenosis, and (4) Fallot's tetralogy.     

microRNA-184在小儿先天性心脏病中的表达及其与心肌细胞的关系

目的：研究先天性心脏病（ congenital heart disease, CHD）患者的心肌组织中microRNA?184表达水平及其与心肌细胞的相关性。方法采用microRNA （ miRNAs）芯片技术和RT?PCR检测40例先天性心脏病患儿和10例心脏正常患儿心肌组织中microRNA?184的表达,同时应用原位TUNEL观察心肌细胞的凋亡情况。结果先天性心脏病患儿的心肌组织中的microRNA?184表达下调, RT?PCR的验证结果与microR?NA芯片技术的实验结果一致;伴随着microRNA?184的低表达,先天性心脏病患儿的心肌细胞凋亡增加。结论在先天性心脏病患儿的心肌组织中microRNA?184表达下调; microRNA?184的表达与心肌细胞的凋亡情况成负相关,对心肌细胞有保护作用。     

先天性心脏病并发肺动脉高压患者血浆前列腺素E_2的变化及意义

对２７例左向右分流先天性心脏病病人及１２例非癌症普胸病人，用放射免疫分析测定了血浆前列腺素Ｅ２（ＰＧＥ２），结果发现先心病肺高压组病人的血浆ＰＧＥ２（３２．０±５．２ｎｇ／Ｌ），显著高于无肺高压组（２３．０±４．４ｎｇ／Ｌ）及普胸对照组的（１９．１±３．９ｎｇ／Ｌ）；且轻度肺高压组（３０．９±４．８ｎｇ／Ｌ）及中重度肺高压组（３３．０±８．３ｎｇ／Ｌ）血浆ＰＧＥ２均显著高于无肺高压组的，而轻度肺高压组和中重度肺高压组血浆ＰＧＥ２比较，则差异不显著。先心病肺高压病人血浆ＰＧＥ２的增加，可能是对肺动脉压力升高的一种代偿机制，而肺动脉高压的发病是代偿不全及其它因素作用的结果。     

Genetic and Functional Analyses of ZIC3 Variants in Congenital Heart Disease

Mutations in zinc‐finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc‐finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N‐ and C‐terminal mutations has, however, prevented similar analyses in these regions. Notably, an N‐terminal polyalanine expansion was recently identified in a patient with VACTERL, suggesting a potentially distinct function for this domain. Here we report ZIC3 sequencing results from 440 unrelated patients with heterotaxy and CHD, the largest cohort yet examined. Variants were identified in 5.2% of sporadic male cases. This rate exceeds previous estimates of 1% and has important clinical implications for genetic testing and risk‐based counseling. Eight of 11 were novel, including 5 N‐terminal variants. Subsequent functional analyses included four additional reported but untested variants. Aberrant cytoplasmic localization and decreased luciferase transactivation were observed for all zinc‐finger variants, but not for downstream or in‐frame upstream variants, including both analyzed polyalanine expansions. Collectively, these results expand the ZIC3 mutational spectrum, support a higher than expected prevalence in sporadic cases, and suggest alternative functions for terminal mutations, highlighting a need for further study of these domains.     

Interpretation Bias for Heart Sensations in Congenital Heart Disease and its Relation to Quality of Life

Background: Previous studies have shown that patients with congenital heart disease (ConHD) report a diminished health-related quality of life. Purpose: This study examines the mechanisms by which ConHD affects health-related quality of life. We hypothesize that (1) the relation between trait anxiety and quality of life is mediated by a negative interpretation bias for heart sensations, specifically in ConHD, and that (2) the relation between trait anxiety and interpretation bias is mediated by state anxiety. Method: Sixty-six patients with ConHD and 50 healthy participants read a vignette about a person experiencing ambiguous heart-related sensations. Interpretation bias to these sensations was assessed with the Implicit Models of Illness Questionnaire. Participants completed Spielberger trait and state anxiety questionnaires and the physical subscales of a quality-of-life questionnaire. Results: Path-analysis demonstrated that interpretation bias mediated the relation between trait anxiety and daily functioning. However, trait anxiety and interpretation bias were less influential with respect to gross motor functioning. Moreover, state anxiety mediated the relation between trait anxiety and interpretation bias. Conclusion: These results suggest that patients with ConHD who display both elevated levels of trait and state anxiety exhibit the most pronounced negative interpretation bias for heart sensations and in turn diminished daily functioning. The authors gratefully acknowledge Conor Dolan and Jelte Wicherts for their statistical advice and Kiki Hohnen for her grammatical advice. The report was written as part of a project funded by the Dutch Heart Foundation (99.038).     

42例老年冠心病临床与病理对比分析

对比分析42例老年冠心病的临床与病理资料。结果表明:心电图对心肌缺血的诊断符合率为79.0％,对心肌肥厚的诊断符合率为52.0％。其中31例血脂增高者以甘油三酯更明显。血脂水平与冠状动脉阻塞程度无关。伴有高血压组的心脏重量、左室后壁厚度明显高于非高血压组。多数病人的临床表现与冠脉关系密切,但也有冠脉几乎阻塞而缺乏临床症状者。8例170岁以上心肌梗塞患者的临床及病理特点为:冠脉受累支数多,冠脉阻塞以环形狭窄为主,多伴有斑块出血,可无心绞痛,易伴意识丧失,并发症较多,易发生猝死。     

Major Adverse Cardiovascular Events in Korean Congenital Heart Disease Patients: A Nationwide Age- and Sex-Matched Case-Control Study

PurposeCongenital heart disease (CHD) is a known risk factor for acquired cardiovascular and cerebrovascular diseases. However, available evidence on CHD is limited mostly to Western populations. This study aimed to evaluate the prevalence of vascular events and all-cause mortality in Korean patients with CHD and to further corroborate CHD as a predictor of vascular events and all-cause mortality.Materials and MethodsThe claims data of the Korean National Health Insurance Service (NHIS) were retrospectively reviewed. Information regarding diagnostic codes, comorbidities, medical services, income level, and residential area was also collected. Outcomes of interest included stroke, myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE).ResultsWe included 232203 patients with CHD and 3024633 individuals without CHD as a control group through age- and sex-matched 1:10 random sampling. The prevalences of hypertension, congestive heart failure, ischemic heart disease, hyperlipidemia, and atrial fibrillation were significantly higher in the CHD group, which had a more than two-fold higher incidence of vascular events and all-cause mortality, than in the group without CHD. Multivariable models demonstrated that CHD was a significant risk factor for stroke, MI, all-cause mortality, and MACE.ConclusionIn conclusion, this nationwide study demonstrates that Korean patients with CHD have a high incidence of comorbidities, vascular events, and mortality. CHD has been established as an important predictor of cardiovascular events. Further studies are warranted to identify high-risk patients with CHD and related factors to prevent vascular events.     

心脏特异转录因子NKX2-5、TBX5、GATA4与先天性心脏病的研究进展

许多基因严格时空顺序的表达调控着心脏的正常发育,其中任一个基因的异常都可能导致先天性心脏病的发生。NKX2-5、TBX5、GATA4是心脏早期发育中最重要的3个转录因子,三者质或量的异常均会导致心脏畸形。大量研究提示,三者存在着复杂的相互作用,且位于许多基因的上游,可能以复合体的形式调控着心脏中许多转录因子的正确表达。本文对其特点、功能及可能的作用机制做一综述。     

Association of Chromosome 9p21 Genetic Variants with Risk of Coronary Heart Disease in the East Asian Population: A Meta‐Analysis

Our aim was to evaluate the effect of SNPs in the 9p21 locus on genetic susceptibility of coronary heart disease in the East Asian population. We searched PubMed, EMBASE and CNKI for publications relating to the association between SNPs within the 9p21 locus and coronary heart disease in the East Asian population. This meta‐analysis was assessed by STATA 9.2. Twenty‐one studies from 15 eligible papers composing 25,945 cases and 31,777 control subjects were included in the meta‐analysis. The odds ratio (OR) and 95% confidence interval (CI) for the risk allele was 1.30 (1.25–1.35) with moderate heterogeneity. No publication bias was observed in this study. Sensitivity analysis further strengthened the validity of this association. In conclusion, SNPs within the 9p21 locus were strongly associated with the risk of coronary heart disease in the East Asian population with a similar risk OR to the Caucasian population.