The extent of the raphe in bicuspid aortic valves is associated with aortic regurgitation and aortic root dilatation

Background

The clinical course of bicuspid aortic valves (BAVs) is variable. Data on predictors of aortopathy and valvular dysfunction mainly focus on valve morphology.

Aim

To determine whether the presence and extent of the raphe (fusion site of valve leaflets) is associated with the degree of aortopathy and valvular dysfunction in patients with isolated BAV and associated aortic coarctation (CoA).

Methods

Valve morphology and aortic dimensions of 255 BAV patients were evaluated retrospectively by echocardiography.

Results

BAVs with a complete raphe had a significantly higher prevalence of valve dysfunction (especially aortic regurgitation) than BAVs with incomplete raphes (82.9 vs. 66.7 %, p = 0.01). Type 1A BAVs (fusion of right and left coronary leaflets) and complete raphe had larger aortic sinus diameters compared with the rest of the population (37.74 vs. 36.01, p = 0.031). Patients with CoA and type 1A BAV had significantly less valve regurgitation (13.6 vs. 55.8 %, p < 0.001) and smaller diameters of the ascending aorta (33.7 vs. 37.8 mm, p < 0.001) and aortic arch (25.8 vs. 30.2 mm, p < 0.001) than patients with isolated BAV.

Conclusions

Type 1A BAV with complete raphe is associated with more aortic regurgitation and root dilatation. The majority of CoA patients have incomplete raphes, associated with smaller aortic root diameters and less valve regurgitation.     

Family screening in patients with isolated bicuspid aortic valve: Restriction to those with aortic dilatation is not justified

AimTo determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only.MethodsDuring follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening.ResultsFrom 2012–2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4–83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62–8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16–1.66).ConclusionScreening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.     

Maternal uniparental disomy 14 dissection of the phenotype with respect to rare autosomal recessively inherited traits, trisomy mosaicism, and genomic imprinting

The phenotype of maternal uniparental disomy of chromosome 14 (upd(14)mat) is characterized by pre and postnatal growth retardation, early onset of puberty, joint laxity, motor delay, and minor dysmorphic features of the face, hands, and feet. Based on a clinical analysis of 24 cases extracted from the literature the phenotype of upd(14)mat was dissected with respect to each symptom's most likely primary causative: trisomy mosaicism, rare autosomal recessively inherited traits, and the impact of known imprinted genes located on chromosome 14q32. As a result, primary factors are confined placental mosaicism for prenatal growth retardation and one or more imprinted genes, which contribute to the reduced final height by accelerated skeletal maturation. As a secondary effect the latter might also cause early onset of puberty. Other secondary effects might be postnatal adaptation problems associated with neurological deficits such as muscular hypotonia due to premature delivery and reduced birthweight and most dysmorphic features as a consequence of subtle skeletal abnormalities and muscular hypotonia. Considering the rarity of traits such as cleft palate, trisomy mosaicism in the fetus is more likely causative than homozygosity of autosomal recessively inherited mutations. Totally, the variable phenotype of upd(14)mat is mainly the consequence of trisomy mosaicism and genomic imprinting. Rare traits might be due to homozygosity of autosomal recessively inherited mutations.     

Prosthetic valves in adult patients with congenital heart disease: Rationale and design of the Dutch PROSTAVA study

Background

Data on long-term complications in adult patients with congenital heart disease (ACHD) and a prosthetic valve are scarce. Moreover, the influence of prosthetic valves on quality of life (QoL) and functional outcome in ACHD patients with prosthetic valves has not been studied.

Objectives

The primary objective of the PROSTAVA study is to investigate the relation between prosthetic valve characteristics (type, size and location) and functional outcome as well as QoL in ACHD patients. The secondary objectives are to investigate the prevalence and predictors of prosthesis-related complications including prosthesis-patient mismatch.

Methods

The PROSTAVA study, a multicentre cross-sectional observational study, will include approximately 550 ACHD patients with prosthetic valves. Primary outcome measures are maximum oxygen uptake during cardiopulmonary exercise testing and QoL. Secondary outcomes are the prevalence and incidence of valve-related complications including prosthesis-patient mismatch. Other evaluations are medical history, physical examination, echocardiography, MRI, rhythm monitoring and laboratory evaluation (including NT-proBNP).

Implications

Identification of the relation between prosthetic valve characteristics in ACHD patients on one hand and functional outcome, QoL, the prevalence and predictors of prosthesis-related complications on the other hand may influence the choice of valve prosthesis, the indication for more extensive surgery and the indication for re-operation.     

The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome

The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (GH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of Ox, at a conventional and low dosage, on behavior, aggression, romantic and sexual interest, mood, and gender role in GH-treated girls with TS, a randomized, placebo-controlled, double-blind study was conducted. 133 patients were treated with GH (1.33 mg/m²/d) from baseline, combined with placebo (Pl), Ox 0.03 mg/kg/d, or Ox 0.06 mg/kg/d from the age of eight, and with estrogens from the age of 12. The child behavior checklist (CBCL), Junior Dutch Personality Questionnaire (DPQ-J), State-subscale of the Spielberger's State-Trait Anger Scale, Romantic and Sexual Interest Questionnaire, Mood Questionnaire, and Gender Role Questionnaire were filled out before, during, and after discontinuing Ox/Pl. The changes during Ox/Pl therapy were not significantly different between the dosage groups. In untreated patients, the mean CBCL total (P = 0.002) and internalizing (P = 0.003) T scores, as well as the mean DPQ-J social inadequacy SD score (SDS) (P = 0.004) were higher than in reference girls, but decreased during GH + Ox/Pl therapy (P < 0.001, P = 0.05, P < 0.001, respectively). Whereas the mean total (P = 0.01) and internalizing (P < 0.001) T score remained relatively high, the mean social inadequacy SDS became comparable with reference values. We conclude that in GH-treated girls with TS, Ox 0.03 mg/kg/d or 0.06 mg/kg/d does not cause evident psychological virilizing side effects. Problem behavior, frequently present in untreated girls with TS, decreases during therapy, but total and internalizing problem behavior remain increased.     

DSCR1 gene expression is dependent on NFATc1 during cardiac valve formation and colocalizes with anomalous organ development in trisomy 16 mice

The Down syndrome critical region 1 (DSCR1) gene is present in the region of human chromosome 21 and the syntenic region of mouse chromosome 16, trisomy of which is associated with congenital heart defects observed in Down syndrome. DSCR1 encodes a regulatory protein in the calcineurin/NFAT signal transduction pathway. During valvuloseptal development in the heart, DSCR1 is expressed in the endocardium of the developing atrioventricular and semilunar valves, the muscular interventricular septum, and the ventricular myocardium. Human DSCR1 contains an NFAT-rich calcineurin-responsive element adjacent to exon 4. Transgenic mice generated with a homologous regulatory region of the mouse DSCR1 gene linked to lacZ (DSCR1(e4)/lacZ) show gene activation in the endocardium of the developing valves and aorticopulmonary septum of the heart, recapitulating a specific subdomain of endogenous DSCR1 cardiac expression. DSCR1(e4)/lacZ expression in the developing valve endocardium colocalizes with NFATc1 and, endocardial DSCR1(e4)/lacZ, is notably reduced or absent in NFATc1(-/-) embryos. Furthermore, expression of the endogenous DSCR1(e4) isoform is decreased in the outflow tract of NFATc1(-/-) hearts, and the DSCR1(e4) intragenic element is trans-activated by NFATc1 in cell culture. In trisomy 16 (Ts16) mice, expression of endogenous DSCR1 and DSCR1(e4)/lacZ colocalizes with anomalous valvuloseptal development, and transgenic Ts16 hearts have increased beta-galactosidase activity. DSCR1 and DSCR1(e4)/lacZ also are expressed in other organ systems affected by trisomy 16 in mice or trisomy 21 in humans including the brain, eye, ear, face, and limbs. Together, these results show that DSCR1(e4) expression in the developing valve endocardium is dependent on NFATc1 and support a role for DSCR1 in normal cardiac valvuloseptal formation as well as the abnormal development of several organ systems affected in individuals with Down syndrome.     

尼可地尔联合冠状动脉心脏介入治疗冠心病合并肾功能不全的疗效及对NGAL、Cys-C的影响

摘要 目的：探析冠心病（CHD）合并肾功能不全（RI）应用冠状动脉心脏介入治疗（PCI）联合尼可地尔的临床疗效及对胱抑素C（Cys-C）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）影响。方法：选择本院2019年6月~2021年6月就诊的86例CHD合并RI患者,随机数字表法分为两组各43例。 两组均实施PCI治疗,对照组实施常规静脉水化处理,观察组联合尼可地尔治疗。对比两组PCI治疗前后24 h肾功能指标（Cys-C、NGAL）、血清炎性因子指标（高敏C反应蛋白 (hs-CRP)、白细胞介素 6 (IL-6)）、心肌损伤指标（心肌肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB））、并发症发生率。结果：观察组CIN发生率（2.33%）、MACE率（2.33%）均明显低于对照组（16.28%、13.95%）,有统计学差异（P<0.05）。两组PCI治疗前Cys-C、NGAL、hs-CRP、IL-6、cTnI、CK- MB无统计学差异（P<0.05）。治疗后观察组Cys-C、NGAL、hs-CRP、IL-6升高幅度、组cTnI、CK- MB明显低于对照组（P<0.05）。结论：PCI 联合尼可地尔应用于CHD合并RI临床治疗效果显著,可有效改善患者肾功能,降低炎症反应、心肌损伤,预防CIN发生。     

Early N-terminal pro-B-type natriuretic peptide is associated with cardiac complications and function during pregnancy in congenital heart disease

Netherlands Heart Journal - Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 20&nbsp;weeks’ gestation predict adverse cardiovascular (CV) complications during...     

先天性心脏病患儿围术期输血与术后肺损伤的相关性研究

目的:研究先天性心脏病患儿围术期输血与术后发生肺损伤的相关性。方法:选择我院诊治的120例先天性心脏病患儿,均在体外循环下进行手术矫治。根据患儿术后是否出现肺损伤分为无肺损伤组(n=97例)与肺损伤组(n=23例)。比较两组一般资料,比较不同围术期输血浆量及输血量患儿的术后肺损伤发病率;采用多因素logistic回归对术后肺损伤与围术期输血浆量、围术期输血量、最低红细胞压积(30%)、体外循环时间(80 min)、年龄(≤1岁)以及最低温度之间的相关性进行分析。结果:无肺损伤组与肺损伤组患儿性别间无显著差异(P0.05);肺损伤组患儿年龄、体质量均显著低于无肺损伤组患儿(P0.05),而围术期输血浆量、围术期输血量、最低血红积压、体外循环时间均显著高于无肺损伤组患儿(P0.05)。随着患儿围术期输血浆量及输血量的增加,患儿术后肺损伤的发病率越高(P0.05);多因素logistic回归分析显示围术期输血浆量、围术期输血量、最低红细胞压积(30%)、体外循环时间(80 min)以及年龄(≤1岁)是患儿发生术后肺损伤的独立危险因素(P0.05)。结论:围术期输血浆量以及输血量与先天性心脏病患儿术后肺损伤的发生紧密相关,围术期输血浆量以及输血量越多,肺损伤的发生风险就越高,建议临床上开展多种节约用血措施。     

Age-dependent mobilization of circulating endothelial progenitor cells in infants and young children undergoing cardiac surgery with cardiopulmonary bypass

This study was designed to find the effects of age on circulating endothelial progenitor cells (EPCs) and their mobilization in infants and young children following surgical correction of congenital heart defects. In 60 consecutive infants and young children (1 month to 3 years old) undergoing repair of atrial/ventricular septal defect, the numbers of EPCs and plasma levels of IL-6, -8, -10, TNF-α, VEGF and G-CSF were determined preoperatively, at the end of cardiopulmonary bypass (CPB), as well as 6, 12, 24, 48, 72 and 96 h following surgery. Preoperative EPCs were reduced with increased age, similar to changes in plasma VEGF and G-CSF levels. Rapid mobilizations of EPCs and plasma VEGF, G-CSF were induced by cardiac surgery with CPB in all infants and young children, and the increased volumes of EPCs, VEGF and G-CSF decreased with age decreasing. The increased volumes of IL-6, -8, -10 and TNF-α were similar in different age groups. However, mobilization of EPCs, plasma VEGF and G-CSF were limited in infants <6 months old, which did not correlate with change in inflammatory IL activation. Preoperative EPCs and plasma levels of VEGF and G-CSF were reduced with increasing age in infants and young children. Although a significant increase in EPCs and release of cytochemokines were observed in infants undergoing CPB, the mobilization of EPCs of the infants <6 months old are limited.     

先天性心脏病"双期三步法"筛查诊断流程推广应用初探

摘要 目的：分析"双期三步法"筛查诊断流程在西安咸阳地区新生儿先天性心脏病筛查中的推广与应用价值。方法：选取2021年1月1日-2021年12月31日在医院产检的胎儿和出生的新生儿作为研究对象，收集胎儿期、新生儿期和婴儿期的先心筛查数据，将新生儿分为杂音组、经皮氧饱和度阳性组、双阳性组，评价"双期三步法"筛查方法的使用价值。结果：共对12318例新生儿进行了筛查，筛查阳性497例。确诊126例，实际发病率为10.23‰。在确诊的例先心病患儿中，位于前3位的疾病类型分别为房间隔缺损66例（52.38%），室间隔缺损41例（32.54%），动脉导管未闭11例（8.73%）。杂音组184例，单纯心脏杂音筛查检出率1.49%，灵敏度为82.5%，特异度为99.3%。经皮氧饱和度阳性组147例，单纯经皮氧饱和度阳性筛查检出率1.19%，灵敏度为58.7%，特异度为99.4%。双阳性组166例，两项指标联合筛查检出率1.35%，灵敏度为94.4%，特异度为99.6%。结论："双期三步法"筛查诊断流程特别是心脏听诊和经皮氧饱和度联合筛查有利于早期发现新生儿CHD，值得推广应用。     

平衡超滤技术对小儿先心病术后炎症因子、凝血功能及肺功能的影响

目的:探讨平衡超滤技术对小儿先心病术后炎症因子、凝血功能及肺功能的影响。方法:选择2014年9月至2017年9月我院接诊的100例先天性心脏病患儿进行研究,通过随机数表法分为观察组55例和对照组45例,两组均于体外循环下实施心内直视手术,观察组在体外循环启动后患儿复温时开始平衡超滤,并于体外循环结束后即刻进行改良超滤,对照组仅在体外循环结束后即刻进行改良超滤。比较两组不同时间点炎症因子、凝血功能及肺功能的变化、术后恢复情况及并发症。结果:于体外循环结束后(术后)20 min(T1)、术后2 h(T2)、术后6 h(T3)各时点,观察组血清肿瘤坏死因子(TNF)-α、白介素(IL)-6、IL-10均明显比对照组低(P<0.05);观察组各时点活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)均明显低于对照组(P<0.05);观察组各时点肺静脉顺应性(Cstat)、氧合指数(OI)在各时点均明显高于对照组,肺泡-动脉氧分压梯度(AaDO2)明显低于对照组(P<0.05);观察组血管活性药使用时间、呼吸机使用时间和ICU住院时间均明显比对照组短(P<0.05),观察组感染、弥散性血管性凝血、肺功能损伤等发生率明显低于对照组(P<0.05)。结论:在改良超滤技术上,联合平衡超滤更有助于减轻小儿先心病术后炎症因子的释放,具有较好的凝血功能、肺功能保护作用,可有效促进术后恢复,减少围术期并发症。     

The 105-kDa protein component of Bacillus cereus non-haemolytic enterotoxin (Nhe) is a metalloprotease with gelatinolytic and collagenolytic activity

The integration site(s) of the IncJ element, R391, was localised to a specific region of the Escherichia coli chromosome, between the uxuA and serB loci (98.0-99.5 min), using classical Hfr mapping techniques. F-prime plasmid hosts, diploid for regions spanning the E. coli chromosome, were used as recipients in R391 and R997 conjugal transfer assays. Analysis of transconjugants revealed the integration of R391 and R997 into specific F-primes that contain the uxuA to serB region, but not F-primes that contain other regions of the chromosome. A comparison of the electrophoretic mobility of the original F-primes with those containing inserts demonstrated the integration of large elements, in excess of 85 kb. Linear integration of the IncJ elements into chromosomal DNA was demonstrated in recombination-deficient (recA) backgrounds in the absence of detectable autonomous stages. These observations account for the inability to isolate plasmid DNA from IncJ hosts, and suggests that the elements exhibit a conjugative transposon-like biology in E. coli.     

先天性心脏病患儿术后并发医院感染的危险因素及其病原菌分布和药敏实验分析

目的:统计先天性心脏病(CHD)患儿术后医院感染的病原菌分布及细菌耐药性情况,分析影响CHD患儿术后医院感染的危险因素。方法:回顾性选取2010年3月-2017年10月我院行CHD手术治疗的患儿3800例,收集临床标本进行致病菌培养并进行药敏试验,统计CHD术后医院感染患儿病原菌种类及主要致病菌的耐药情况,分析影响CHD患儿术后医院感染的危险因素。结果:3800例CHD患儿术后医院感染率为3.13%(119/3800),共分离出菌株172株,G^-菌、G⁺菌、真菌分别占55.81%(96/172)、26.74%(46/172)、17.44%(30/172)。肺炎克伯雷菌、大肠杆菌对头孢类抗生素高度耐药,鲍曼不动杆菌检出率逐年增高,且仅对多黏菌素B保持敏感;肺炎链球菌、凝固酶阴性葡萄球菌、金黄色葡萄球菌对大环内脂类抗生素、克林霉素、青霉素高度耐药,对万古霉素和替加环素保持敏感。术后医院感染与年龄、体重、病程、手术时间、体外循环时间、机械通气时间、ICU停留时间、住院时间、合并肺动脉高压、吸痰次数、静脉营养、应用丙种球蛋白或白蛋白有关(P<0.05),且合并肺动脉高压、体外循环时间≥100 min、机械通气时间≥120 h、吸痰次数≥5次/d是CHD患儿术后医院感染的危险因素(P<0.05)。结论:G^-菌、G⁺菌是CHD患儿术后医院感染的主要致病菌,且对常用抗生素高度耐药,此外鲍曼不动杆菌的检出率和耐药性上升极为明显,合并肺动脉高压、体外循环时间及机械通气时间过长、吸痰次数多的CHD患儿医院感染风险升高。     

Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome

Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal forebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons has been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain. The present study examined the interrelationship between reductions in CBF/trkA-containing neurons and the overexpression of galaninergic fibers within the nucleus basalis in DS. Within the nucleus basalis stereologic evaluation revealed a 46% reduction in the number of trkA-immunopositive neurons, whereas optical density measurements displayed a nonsignificant 18% reduction in neuronal trkA immunoreactivity in DS as compared with age-matched controls. Western blot analysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleus basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant reduction in trkA within the nucleus basalis and cortex with only a moderate hypertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD basal forebrain.     

The effect of disease on human cardiac protein expression profiles in paired samples from right and left ventricles

Background

Cardiac diseases (e.g. coronary and valve) are associated with ventricular cellular remodeling. However, ventricular biopsies from left and right ventricles from patients with different pathologies are rare and thus little is known about disease-induced cellular remodeling in both sides of the heart and between different diseases. We hypothesized that the protein expression profiles between right and left ventricles of patients with aortic valve stenosis (AVS) and patients with coronary artery disease (CAD) are different and that the protein profile is different between the two diseases. Left and right ventricular biopsies were collected from patients with either CAD or AVS. The biopsies were processed for proteomic analysis using isobaric tandem mass tagging and analyzed by reverse phase nano-LC-MS/MS. Western blot for selected proteins showed strong correlation with proteomic analysis.

Results

Proteomic analysis between ventricles of the same disease (intra-disease) and between ventricles of different diseases (inter-disease) identified more than 500 proteins detected in all relevant ventricular biopsies. Comparison between ventricles and disease state was focused on proteins with relatively high fold (±1.2 fold difference) and significant (P < 0.05) differences. Intra-disease protein expression differences between left and right ventricles were largely structural for AVS patients and largely signaling/metabolism for CAD. Proteins commonly associated with hypertrophy were also different in the AVS group but with lower fold difference. Inter-disease differences between left ventricles of AVS and CAD were detected in 9 proteins. However, inter-disease differences between the right ventricles of CAD and AVS patients were associated with differences in 73 proteins. The majority of proteins which had a significant difference in one ventricle compared to the other pathology also had a similar trend in the adjacent ventricle.

Conclusions

This work demonstrates for the first time that left and right ventricles have a different proteome and that the difference is dependent on the type of disease. Inter-disease differential expression was more prominent for right ventricles. The finding that a protein change in one ventricle was often associated with a similar trend in the adjacent ventricle for a large number of proteins suggests cross-talk proteome remodeling between adjacent ventricles.