Noncompaction Of Ventricular Myocardium Research Articles

A case report of isolated right ventricular noncompaction with mutation of ACVRL1: a new cause of noncompaction of ventricular myocardium?

BackgroundNoncompaction of ventricular myocardium(NVM) is a rare kind of cardiomyopathy associated with genetic mutations and nongenetic factors, among which the isolated right ventricular noncompaction (iRVNC) is the most rare type. ACVRL1 is the pathogenic gene of type 2 hereditary hemorrhagic telangiectasia (HHT2), and there’s no NVM reported to be associated with ACVRL1 mutation.Case presentationThis is a rare case diagnosed as iRVNC and pulmonary hypertention with ACVRL1 mutation detected.ConclusioniRVNC in this case may be due to ACVRL1 mutation, secondary to pulmonary hypertention and right ventricular failure caused by ACVRL1 mutation, or they happened in the same case coincidently.

Multiple subtypes of coxsackievirus group B can cause congenital heart disease.

Different serotypes of coxsackievirus B (CVB), which is the most common cause of viral myocarditis, target cardiomyocytes through Coxsackie and Adenovirus Receptor and Decay-Accelerating Factor. Both receptors are expressed in the fetal heart. We hypothesized that infection with different serotypes of CVB during early pregnancy plays a role in pathogenesis of congenital heart defect (CHD). In this study, we use a murine model to infect with CVB1, CVB4, and combination of CVB3 + CVB4 during a critical period in gestation. We examined offspring of pregnant mice for fetal death and heart defects following viral infection. Fetuses from uninfected control dams showed normal heart development, while maternal CVB infection precipitates CHD: majorly ventricular septal defects (VSD) and non-compaction of ventricular myocardium (NC), with some infrequent cases of double outlet right ventricle, left ventricle wall rupture, right ventricle hypertrophy, and thickened/dysplastic semilunar valves. Infection of pregnant dams with CVB1 leads to 44% VSD and 41.2% NC cases, while with CVB4 leads to 31.7% VSD and 13.3% NC cases. Co-infection with CVB3 + CVB4 increases fetal pathology to 51.3% VSD and 41% NC cases. Infection can also result in fetal death, with higher incidences with CVB3 + CVB4 with 46.2% cases, compared to 33.3% by CVB1 and 21.7% by CVB4. Male fetuses were more susceptible to all phenotypes. Our report shows that prenatal CVB infections can lead to pathogenesis of certain heart defects in mouse model, particularly exacerbated with co-infections. This data confirms a link between prenatal CVB infection and CHD development and highlights it is not unique to just one serotype of CVB.

Left ventricular non-compaction with symptomatic coronary artery disease

Left ventricular (LV) non-compaction of ventricular myocardium (NCVM) is a form of genetic cardiomyopathy resulting in failure of trabecular compaction of the developing myocardium. Patients with NCVM can be asymptomatic or present with progressive LV systolic dysfunction and/or ventricular arrhythmias.

Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium

SummaryThe serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5−/−) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5−/− mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development.

Splicing Factor SRSF5 Deletion Disrupts Alternative Splicing and Causes Noncompaction of Ventricular Myocardium

Splicing Factor SRSF5 Deletion Disrupts Alternative Splicing and Causes Noncompaction of Ventricular Myocardium

Analysis of Clinical Characteristics of Patients with Heart Failure and Intracardiac Thrombosis

Aims Our study summarized and analyzed the clinical characteristics and thrombosis distribution of patients diagnosed with both Heart failure(HF) and intracardiac thrombosis, and explored the clinical characteristics of this kind of patients. Methods Patients who were diagnosed HF combined with intracardiac thrombosis and admitted in Fuwai Hospital from October 2008 to May 2018 were enrolled in this study. Demographics characteristics, vital signs, complications, laboratory tests, data about thrombosis, echocardiography data and medication usage were collected. The relationship between the baseline characteristics, basic heart disease, cardiac function and thrombosis distribution were analyzed. At the same time, the application of anticoagulant drugs in this population was analyzed and summarized. Results A total of 1248 patients were enrolled in this study, of which 72.2% were male. The incidence of left ventricular thrombosis is the highest (66.8%). Besides, thrombi located in the left heart were more common than that in right heart. And there were more ventricular thrombi than atrial thrombi. The most common complications were coronary atherosclerotic heart disease (57.5%), followed by hypertension (39.4%), non-ischemic heart disease (36.2%), and atrial fibrillation/atrial flutter (35%). Transthoracic cardiac ultrasound was the main way to diagnose HF combined with intracardiac thrombosis (75.1%). The rate of anticoagulant usage in these patients was 56.8%, and warfarin was the most commonly used (45.1%). The location of thrombosis was related to the basic heart disease and cardiac function. In the HF patients with coronary heart disease, noncompaction of ventricular myocardium and dilated cardiomyopathy, intracardiac thrombosis mostly occurred in the left ventricle. In the HF patients with atrial fibrillation/atrial flutter, hypertrophic cardiomyopathy, restrictive cardiomyopathy and valvular heart disease, the main site of intracardiac thrombosis was the left atrium. Patients with HF and restrictive cardiomyopathy had the highest incidence of right atrial thrombosis. The lower the LVEF, the higher the incidence of left ventricular and left atrium thrombosis (p Conclusion It is common in patients with HF to develop intracardiac thrombosis, and the distribution characteristics of intracardiac thrombosis have certain rules. The left ventricle is the most common site of thrombosis in patients with HF, and should be paid more attention to in clinical work practice.

Non-compaction of ventricular myocardium in children

Non-compaction of ventricular myocardium (NVM), a rare congenital and inherited cardiomyopathy, is characterized by prominent trabeculations and deep intertrabecular recesses in communication with the ventricular cavity.NVM has diverse clinical presentations without specificity, of which the major characteristics are cardiac insufficiency, arrhythmias and thrombosis.Echocardiography and cardiac magnetic resonance imaging are necessary technologies to diagnose NVM.Symptomatic therapy is the only choice for most patients.Furthermore, if medical treatment fails, the heart transplantation could be performed.As a whole, NVM has a high mortality and entirely different prognosis, however, the prognosis of asymptomatic patients is relatively good. Key words: Non-compaction of ventricular myocardium; Cardiac insufficiency; Arrhythmia; Thrombosis

Left Ventricular Noncompaction with Bicuspid Aortic Valve: A Case Report with a Comprehensive Cardiac MRI Approach

: Noncompaction of ventricular myocardium, once thought to represent a rare cardiomyopathy, is being diagnosed with increased frequency. It is often accompanied by various congenital heart diseases. Coexisting valvular anomalies are an emerging issue that requires further investigation in patients with noncompaction cardiomyopathy, because they can increase the potential for adverse clinical events. This article describes the case of a 45-year-old male diagnosed with left ventricular noncompaction (LVNC) with a bicuspid aortic valve. Progressive deterioration of cardiac function in this patient could be explained by myocardial fibrosis and accompanying valvular anomalies on cardiac magnetic resonance imaging (MRI). The clinical implications of cardiac MRI in noncompaction cardiomyopathy are discussed based on its ability to depict both morphological and functional features. Considering the potential for coexisting congenital heart disease to declines in cardiac function, patients with LVNC should be comprehensively evaluated for concurrent cardiac anomalies and myocardial fibrosis.

A de novo Mutation in the MTUS1 Gene Decreases the Risk of Non-compaction of Ventricular Myocardium via the Rac1/Cdc42 Pathway.

Background: The MTUS1 gene encodes a microtubule-associated protein involved in multiple processes including cell polarity and microtubule balance during myocardial development.Aims: To investigate the association between a de novo c. 2617A->C mutation in MTUS1 (NM_001001924.2) and non-compaction of ventricular myocardium (NVM) and explore the potential mechanisms.Methods: A de novo mutation in MTUS1 was identified for a familial pedigree with NVM. Lentiviral vectors containing MTUS1 wild type or the mutation MTUS1 were constructed and co-infected into HEK-293 cells. MTUS1, Rac1/Cdc42, α-tubulin, α/β-tubulin, polarity protein (PAR6), and the morphology of daughter cells were measured by real-time PCR, Western blot, and immunofluorescence assays, respectively.Results: The lentiviral vectors were constructed successfully. Immunofluorescence assays revealed the fluorescence intensity of α-tubulin to be decreased and α/β-tubulin to be increased in the mutation MTUS1 group. The fluorescence intensity of PAR6 was higher and morphology of the daughter cells in the mutation group was different from the wild type group. The phosphorylation of Rac1/Cdc42 in the mutation group was significantly lower than in the wild type group.Conclusions: A de novo mutation in MTUS1 decreased the stability of microtubules and increased cell polarity via the Rac1/Cdc42 pathway, which may partly elucidate the mechanism underlying cellular protection in NVM.

A fetal mouse model of ventricular non-compaction using retinoic acid

ObjectiveTo develop a fetal mouse model of non-compaction of ventricular myocardium (NVM) using All-trans retinoic acid (ATRA). MethodsPregnant mice were divided into blank control group, dimethyl sulfoxide (DMSO) control group and ATRA group. The pregnant mice at 8.5 days after pregnancy were given 70 mg/kg ATRA in DMSO to induce fetal mouse model of NVM in ATRA group. All the hearts were acquired and sliced in short axis from the neonatal mice sacrificed after delivery. Pathological changes were visualized under 40- and 100-fold magnification with Hematoxylin-eosin (HE) staining at different ventricular levels. The criteria for pathological diagnosis of classical NVM were: prominent trabeculations on the endocardial surface and deep intertrabecular recesses communicating with the ventricular cavity and the thickness ratio of non-compacted layer (N) to compact myocardium layer (C) N/C > 1.4. Analysis of variance (ANOVA) and least significant difference (LSD) were used to analyze the differences of three groups, with P < 0.05 considered as significant. ResultsThe typical characteristics of NVM histopathological findings of ATRA fetal mouse were confirmed: compared to the hearts of blank control group (n = 20) and DMSO control group (n = 15), all the hearts of ATRA group (n = 17) showed the obviously thinner compacted layer and the much thicker non-compacted layer. The N/C ratio of left ventricles (LVs) in ATRA group was 2.735 ± 1.634, higher than those in DMSO control group 0.178 ± 0.119 and blank control group 0.195 ± 0.118 with significant difference (F = 32.550, P <0. 0001); N/C ratios of right ventricles (RVs) in the ATRA group were (6.068 ± 4.394), higher than those in the DMSO control group 0.459 ± 0.24 and in the blank control group 0.248 ± 0.182 with significant difference (F = 20.069, P <0.0001). LSD of LVs and RVs showed a significant difference between ATRA and blank control group (P < 0.0001), and between ATRA and DMSO control group (P < 0.0001). LSD showed no significant difference in two control groups of LVs (P = 0.963) and of RVs (P = 0.848) . ConclusionExcess ATRA could be used to induce NVM of fetal mice heart. This animal model might provide a platform for fundamental research of NVM pathogenesis and potential targeting treatment.

Placental P-glycoprotein inhibition enhances susceptibility to Di-(2-ethylhexyl)-phthalate induced cardiac malformations in mice: A possibly promising target for congenital heart defects prevention.

BackgroundsReducing toxicants transplacental rates could contribute to the prevention of congenital heart defects (CHDs). Placental P-glycoprotein (P-gp) plays a vital role in fetal toxicants exposure and subsequently affects the risk of toxicants-induced birth defects. However, data on the role of placental P-gp in decreasing toxicants-induced cardiac anomalies is extremely limited. This study aimed to explore the protective role of placental P-gp in reducing the risk of Di-(2-ethylhexyl)-phthalate (DEHP) induced cardiac anomalies in mice.MethodsThe C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 500mg/Kg DEHP group (n = 15), 3mg/Kg verapamil group (n = 10) and 500mg/Kg DEHP & 3mg/Kg verapamil group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from E6.5–14.5. Maternal weights were monitored every day and samples were collected at E15.5. HE staining was used to examine fetal cardiac malformations. Real-time quantitative PCR (RT-qPCR) and Western-Blot were applied to detect Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. The mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) was also determined using RT-qPCR.ResultsCo-administration of verapamil and DEHP significantly elevated fetal cardiac malformation rates, in comparison with the DEHP group, the verapamil group and the vehicle group. Different phenotypes of cardiac anomalies, including septal defects and ventricular myocardium noncompaction, were noted both in the DEHP group and the DEHP & verapamil group. The ventricular myocardium noncompaction appeared to be more severe in the DEHP & verapamil group. Fetal cardiac PPARγ mRNA expression was notably increased and Gata4/Mef2c/Chf1 expression was markedly decreased in the DEHP & verapamil group.ConclusionPlacental P-gp inhibition enhances susceptibility to DEHP induced cardiac malformations in mice.

Thickness and Ratio of Noncompacted and Compacted Layers of the Left Ventricular Myocardium Evaluated in 56 Normal Fetuses by Two-Dimensional Echocardiography.

The thickness and ratio of noncompacted and compacted layers of the left ventricular (LV) myocardium in the normal fetus were investigated by fetal echocardiography. We aimed to investigate the compaction process of the LV myocardium during the normal gestation period and provide reference for echocardiographic diagnosis of a fetus with ventricular myocardium noncompaction. A total of 56 pregnant women in the gestational period of 23–30 weeks were included. Complete fetal echocardiography was performed with system ultrasonographic examination to exclude congenital heart malformation or extracardiac malformation. All 56 fetuses showed normal development. In the short-axis view of the fetal heart, the LV wall was divided into an upper and lower section at the level of the papillary muscle. Each section was then further divided into four segments, namely, anterior, posterior, lateral, and inferior wall. Thus, the LV wall was divided into eight segments. The thickness of the ventricular noncompacted and compacted layers and the ratio of the ventricular noncompacted to compacted layers of these segments at end-systole were measured and calculated. In echocardiography, the fetal LV myocardium is a two-layered structure: the endocardial noncompact myocardium (NC) with higher echo and the epicardium compact myocardium (C) with lower echo. The noncompacted layer is thinner than the compacted layer in the anterior wall, but thicker than the compacted layers in the posterior, lateral, and inferior wall. With respect to the upper and lower sections of the LV myocardium, the noncompacted layer in each segment of the upper section is thinner than that in each segment of the lower section, whereas the compacted layer of the upper section is thicker than that of the lower section. This study suggests that the densification of the fetal LV myocardium occurs gradually from base to apex and from the anterior to lateral, posterior, and inferior walls. This finding aids in further understanding the process of myocardial densification and provides a diagnostic reference for noncompaction of noncompaction cardiomyopathy (NCCM).

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy.

Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy.Methods:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy.Results:A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.Conclusions:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

Differentiation of patients with two-dimensional echocardiography false positive non-compaction of ventricular myocardium by contrast echocardiography.

Although echocardiography can be used to detect patients with non-compaction of the ventricular myocardium, it is often difficult to diagnose. In this study, the endocardium may be clearly visualized by contrast echocardiography to improve the diagnostic accuracy of patients with noncompaction of the ventricular myocardium. Twenty-four patients (n = 24) suspected with non-compaction of the ventricular myocardium Underwent transthoracic echocardiography including an intracardiac contrast echocardiography. The clinical data, Left ventricular opacification, and contrast echocardiography results were analyzed retrospectively. Twenty-four patients (n = 24) suspected with non-compaction of the ventricular myocardium were classified with transthoracic echocardiography and contrast echocardiography results into two groups: false positive and true positive. There were no significant differences in age, predisposing segments, Left Ventricular End-Diastolic Diameter, Left Ventricular End-Diastolic Volume, Left Ventricular End-Systolic Diameter, Left Ventricular End-Systolic Volume and ejection fraction between the two groups (P>0.05). The thickness ratio of noncompacted to compacted myocardium (N/C) in the true positive group was significantly higher than that in the false positive group (3.47 ± 1.31 vs. 4.96 ± 1.28; P<0.05). The range of noncompact myocardium in non-compaction of the ventricular myocardium patients can be observed clearly by Left ventricular opacification. Contrast medium in trabecular space and crypt is plentiful and ultrasonic contrast is more objective in measuring the thickness of dense myocardium. Two-dimensional echocardiography plays a characteristic role in the diagnosis of non-compaction of the ventricular myocardium; however, some suspected patients were observed to be false positive. Left ventricular opacification can greatly improve the clarity and accuracy of the endocardial margin by enhancing left ventricular imaging, displaying the true dense and non-dense layers, and improve the accuracy of ultrasonic diagnosis of non-compaction of the ventricular myocardium. The purpose of this paper was to explore the applied value of contrast echocardiography for heart diagnosis.

Abstract 565: Coxsackievirus Infection During the First Trimester of Pregnancy Suppresses Cardiomyocyte Proliferation Leading to Congenital Heart Defects

Purpose: Coxsackievirus B (CVB), known to be the most common cause of myocarditis, target cardiomyocytes through Coxsackie and Adenovirus Receptor, which is highly expressed in the fetal heart. We hypothesized that CVB infection during early pregnancy may play a role in the pathogenesis of congenital heart disease (CHD). Methods: Pregnant C57Bl/6J mice were infected with varying doses of CVB3 (Nancy strain), 1x10 6 , 2.5x10 6 , and 5x10 6 TCID50, between embryonic days (E) 5-11. Presence of the virus was confirmed by RT-PCR and infectivity assay. Fetal heart phenotype was assessed by histology. RNA collected from fetal hearts using laser microdissection was analyzed by RNA-Seq to understand changes at the molecular level after infection. Results were confirmed by immunohistochemistry and qPCR. To determine if virus serotype alters the outcome, CVB1, CVB4, and a combination of CVB3 and CVB4 were used for infection. To assess the clinical significance serum from pregnant human subjects, grouped based on outcome of pregnancy (healthy baby vs babies with CHD), was checked for the presence of CVB serotypes. Results: Fetuses developed spectrum of CHD (38.2%, n=78/204): ventricular septal defect, double outlet right ventricle, and non-compaction of ventricular myocardium after CVB3 infection. Approximately one third of the fetuses were resorbed (38.7%, n=129/333). Infection at E9 led to the highest incidence of VSD with female fetuses being more susceptible to the phenotype. Transcripts found to be differentially expressed in hearts with VSDs were mediators of the Transforming growth factor β and Extracellular matrix signaling pathways. Consistent with the former, expression levels of BMP2 and Smad1/5/9 mRNA were elevated in fetal hearts with VSDs. This correlated with suppressed proliferation of cardiomyocytes in these mice. In pregnant human subjects who had babies with CHD elevated titers of antibodies against CVB3, CVB4, and CVB3+CVB4 were seen. In mice, infection with CVB1, CVB4, or CVB3+4 showed that CVB3 in combination with CVB4 induces more VSDs than infection with any one serotype. Conclusion: There is a critical window during pregnancy where CVB infection leads to abnormal cardiac development likely through reduction of cardiomyocyte proliferation.

The effect of maternal exposure to di-(2-ethylhexyl)-phthalate on fetal cardiac development in mice.

Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)-phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250mg kg-1 DEHP group (n = 15), 500mg kg-1 DEHP group (n = 20) and 1g kg-1 DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real-time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator-activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500mg kg-1 and 1g kg-1 ) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation.

Noncompaction of Ventricular Myocardium Involving the Right Ventricle.

Noncompaction ventricular myocardium is an unusual cause of cardiomyopathy. It is association with congenital heart defects, most often with outflow obstructive lesions or coronary anomalies. However, no factor could explain the arrest of development of myocardial structure (isolated form). The pathogenesis of isolated noncompaction is thought to be an arrest in endomyocardial morphogenesis. It has been reported that myocardial noncompaction could present as acquired disease. The most common site of involvement is the left ventricle, with right ventricular involvement being reported in a few cases. In this report, we present a case with noncompaction of the right ventricle (RV). Cardiac computed tomography angiography and magnetic resonance imaging demonstrated morphological abnormalities of the RV.

Clinical and prognosis of the children with noncompaction of ventricular myocardium

Noncompaction of ventricular myocardium (NVM) is reported as a genetic disease characterized by excessively prominent trabeculations and deep intertrabecular recesses.The etiology and pathogenesis are unclear.NVM is a rare disease with poor prognosis.The purpose of this areide is to review NVM manifestations and prognosis,to enhance the awareness of NVM,to improve the diagnosis and treatment,to ensure a better life quality and to increase the lifetime of NVM patients. Key words: Noncompaction of ventricular myocardium; Manifestation; Prognosis; Children

Clinical manifestations of non-compaction of ventricular myocardium in children

Objective To study the clinical characteristics and curing methods of non-compaction of ventricular myocardium(NVM)in children with a view to improve its diagnosis and treatment. Methods From Jan.2009 to Dec.2012, the clinical data, treatment and follow-up of 22 patients with NVM in Beijing Children's Hospital Affiliated to Capital Medical University were analyzed. Results The 22 patients included 13 boys and 9 girls aged from 4 months to 13 years and 3 months with an average age of 3 years and 7 months.Five of them had a family history of cardiac diease.Twenty patients suffered from ventricular dysfunction, with 2 cases at level Ⅰ, 5 cases at level Ⅱ, 7 cases at le-vel Ⅲ and 6 cases at level Ⅳ.Asymptomatic heart murmur was heard in 6 patients and creatine kinase car-diac isoenzymes raise was found in 6 patients.X-ray indicated that heart shadow enlargement and electrocardiographic abnormalities in all 22 patients.Echocardiography features of all cases indicated left ventricular enlargement, and 20 cases of the children had ventricular systolic dysfunction.Left ventricle was detected in 21 patients, while double ventricle dysfunction detected in 1 patient.Thrombus was found in none of the patients.Magnetic resonance imaging was performed in 8 cases of the patients and CT was performed in 14 cases, all of them showed abnormalities.Anti-heart failure medications were administered to 20 patients and aspirin to all of the children.The patients were followed up for 0.5 to 3.0 years.Two patients died from heart failure during the follow-up.In 2 cases whose cardiac ejection fraction was more than 60% had little change of the internal diameter of left ventricle and cardiac function.In 3 cases, the left ventricular diameter narrowed by 3 to 5 millimeter and ejection fraction increased by 5% to 10% over the previous.In 5 cases, the left ventricular diameter expanded by 5 to 7 millimeter and ejection fraction decreased by 3% to 5%.In 10 cases, the left ventricular diameter and heart function had no significant change. Conclusions The main clinical manifestions of NVM in children are cardiac dysfunction, and the prognosis is usually poor.Echocardiography is the principal means of diagnosis.Magnetic resonance imaging can contribute to the diagnosis. Key words: Non-compaction of ventricular myocardium; Cardiac dysfunction; Echocardiography; Child

TACE in perinatal mouse lung epithelial cells promotes lung saccular formation

Tumor necrosis factor-α converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyocytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.