Feasibility and Safety of Transthoracic Echocardiography-Guided Transcatheter Closure of Atrial Septal Defects with Deficient Superior-Anterior Rims

Although previous studies showed that transthoracic echocardiography (TTE) can be used to guide transcatheter closure of atrial septal defect (ASD), whether TTE can be used to guide transcatheter closure of secundum ASD with a deficient superior-anterior rim is unknown and this critical issue was addressed in the present study. A total of 280 patients with secundum ASD who underwent transcatheter ASD closure were recruited and divided into groups A and B depending on ASD superior-anterior rim>4 mm (n = 118) or ≤4 mm (n = 162). TTE was used to guide Amplatzer-type septal occluder (ASO) positioning and assess residual shunt. Procedure success was defined as no, trivial and small residual shunt immediately after the procedure as assessed by color Doppler flow imaging. Group A and group B did not differ in complication rate (8.55% vs.7.55%), procedure success rate (98.3% vs. 95.0%) or complete closure rate immediately after the procedure (89.7% vs. 89.3%) or at 6-month follow-up (98.3% vs. 96.8%). The mean procedure and fluoroscopy time in group B were much longer than those in group A. In conclusion, the absence of a sufficient superior-anterior rim in patients undergoing percutaneous closure of secundum-type ASDs using fluoroscopic and TTE guidance is associated with slightly greater device malposition and migration as well as increased procedural and fluoroscopic times, but the overall complication rate did not differ with TTE guidance when compared to historical controls that used TEE guidance.     

Atrial septostomy benefits severe pulmonary hypertension patients by increase of left ventricular preload reserve

At present, it is unknown why patients suffering from severe pulmonary hypertension (PH) benefit from atrial septostomy (AS). Suggested mechanisms include enhanced filling of the left ventricle, reduction of right ventricular preload, increased oxygen availability in the peripheral tissue, or a combination. A multiscale computational model of the cardiovascular system was used to assess the effects of AS in PH. Our model simulates beat-to-beat dynamics of the four cardiac chambers with valves and the systemic and pulmonary circulations, including an atrial septal defect (ASD). Oxygen saturation was computed for each model compartment. The acute effect of AS on systemic flow and oxygen delivery in PH was assessed by a series of simulations with combinations of different ASD diameters, pulmonary flows, and degrees of PH. In addition, blood pressures at rest and during exercise were compared between circulations with PH before and after AS. If PH did not result in a right atrial pressure exceeding the left one, AS caused a left-to-right shunt flow that resulted in decreased oxygenation and a further increase of right ventricular pump load. Only in the case of severe PH a right-to-left shunt flow occurred during exercise, which improved left ventricular preload reserve and maintained blood pressure but did not improve oxygenation. AS only improves symptoms of right heart failure in patients with severe PH if net right-to-left shunt flow occurs during exercise. This flow enhances left ventricular filling, allows blood pressure maintenance, but does not increase oxygen availability in the peripheral tissue.     

国产房缺封堵器治疗多孔型房缺

目的：评估国产封堵器治疗多孔型房缺的可行性及安全性。方法：在X线及超声引导下对19例多孔型房缺植入国产房缺封堵器,术后常规进行心电图及经胸心脏超声随访半年。结果：所有患者均成功进行了房缺封堵,其中5例放置1枚国产普通型房缺封堵器,7例放置2枚国产普通型房缺封堵器,另7例则分别放置1枚细腰大边型房缺封堵器,术后即刻超声检查1例仍有少许分流,术后1月时随访分流消失,所有患者随访半年未出现明显并发症。结论：国产房缺封堵器可安全应用于多孔型房缺患者的封堵治疗,在经验丰富的先心病介入治疗专科中心,封堵治疗可做为部分多孔型房缺患者的首选治疗。     

经胸超声心动图引导下行房间隔缺损封堵术治疗先天性房间隔缺损的临床研究

目的:探讨经胸超声心动图引导下行房间隔缺损封堵术治疗先天性房间隔缺损(Atrial septal defect,ASD)的临床疗效。方法:比较先天性ASD患者行超声心动图组(49例)或介入组(53例),患者的疗效及心脏功能的变化。结果:超声心动图组并发症发生率显著低于介入组(P0.05);术后4周,两组患者的心率、舒张期室间隔厚度(Interventricular septal thickness,IVST)、左室后壁厚度(Left ventricular posterior wall thickness,LVPWT)、左心室心肌重量(Left ventricular mass,LVM)和左心室心肌重量指数(Left ventricular mass index,LVMI)明显降低(P0.05),左心室射血分数(Left ventricular ejection fraction,LVEF)和左心室高峰充盈率(Left ventricular peak filling rate,LVPFR)均显著升高(P0.05),其余指标则无明显变化(P0.05);但术后1周超声心动图组的LVEF、IVST和LVMI即显著高于术前(P0.05)。结论:胸超声心动图引导下行ASD封堵术与X线介入封堵术疗效相当,但前者可能对ASD患者的心脏功能的改善更为显著。     

Shunt dynamics in experimental atrial septal defects.

Inorder to study the hemodynamic variables involving the magnitude, direction, and timing of phasic shunt flow, both the interatrial pressure gradient and blood flow along with other pertinent hemodynamic variables were measured instantaneously across a surgically created atrial septal defect (ASD) in seven awake dogs. Atrial and ventricular pacing and infusion of phenylephrine and isoproterenol were used to alter hemodynamic conditions. The wave form of phasic ASD flow was similar both in configuration and timing to the interatrial pressure gradient. During the cardiac cycle, both left-to-right (L-R) and right-to-left (R-L) shunting occurred: atrial contraction augmented L-R flow; the onset of ventricular contraction was associated with R-L flow; during the latter part of ventricular contraction, flow returned to L-R with the maximum L-R shunting occurring in early diastole. Tachycardia, infusion of phenylephrine and isoproterenol did not alter the phasic flow pattern. Both spontaneous and positive pressure respiration decreased net L-R shunting.     

Atrial ERK1/2 activation in the embryo leads to incomplete Septal closure: a novel mouse model of atrial Septal defect

Background

MEK1 mutation and activated MAPK signaling has been found in patients with RASopathies and abnormal cardiac development. Previous studies have suggested that regulation of fetal MAPK signaling is essential for normal cardiac development. We investigated the effect of active MEK1 overexpression on fetal atrial septal development.

Methods and results

An inducible double transgenic (DTg) mouse model was developed in which cardiac-specific fetal expression of a constitutively active form of human MEK1 (aMEK1) was induced primarily in the atrium via the withdrawal of doxycycline from the drinking water of pregnant mice. Atrial septal defect (ASD) was found in 51% (23/45) of DTg mice. Fifty-two percent (12/23) of ASD mice died before weaning, and surviving ASD mice exhibited hypertrophic hearts with enlarged right atria and decreased fractional shorting (40?±?2% vs. 48?±?0%, p?<?0.05). The model mimicked human ASD in several key clinical features: severe ASD was associated with growth impairment; ASD-specific mortality was highest within the early postnatal period; despite an even distribution of ASD among the sexes, early mortality was significantly higher in males. The expression of aMEK1 and increased phosphorylation of ERK1/2 was documented via Western blot in DTg fetal hearts, with the largest increases seen in atrial tissue. In an alternative transgenic aMEK1 model with elevated atrial MKP3 expression and corresponding suppression of increases in ERK1/2 phosphorylation, animals did not develop ASD.

Conclusion

This new model of ASD suggests that enhanced atrial MEK1-ERK1/2 signaling during fetal development disrupts normal atrial septation, possibly regulated by the balance of ERK1/2 phosphorylation.

     

Haemodynamic and functional consequences of the iatrogenic atrial septal defect following Mitraclip therapy

Percutaneous MitraClip placement for treatment of severe mitral regurgitation in high surgical risk patients is a commonly performed procedure and requires a transseptal puncture to reach the left atrium. The resulting iatrogenic atrial septal defect (iASD) is not routinely closed, yet the haemodynamic and functional consequences of a persisting defect are not fully understood. Despite positive effects such as acute left atrial pressure relief, persisting iASDs are associated with negative consequences, namely significant bidirectional shunting and subsequent worse clinical outcome. Percutaneous closure of the iASD may therefore be desirable in selected cases. In this review we discuss the available literature on this matter.     

RNT4 3'-UTR insertion/deletion polymorphisms are not associated with atrial septal defect in Chinese Han population: a brief communication

Atrial septal defect (ASD) is a common type of congenital heart disease, which is defined as any communication through atrial septum. Several studies have revealed that genetic factors may influence the susceptibility of ASD. Recent studies have shown that reticulon 4 (RTN4) gene might be involved in some processes relevant to heart development, such as regulation of cell migration and vascular remodeling. This study aimed to evaluate RTN4 gene polymorphisms of CAA and TATC insertion/deletion in relation to the risk of ASD in Chinese Han population. A total of 175 ASD patients and 308 unrelated healthy controls were successfully investigated. The polymorphisms of patients were determined by polymerase chain reaction-polyacrylamide gel electrophoresis. There was no significant difference in the allele frequencies of CAA and TATC insertion/deletion in RNT4 gene between ASD patients and controls. The same results were seen in their genotypes. The present study suggests that CAA and TATC insertion/deletion polymorphisms of RNT4 gene may not be a useful marker to predict the susceptibility of ASD in Chinese Han population.     

Autosomal dominant atrial septal defect of ostium secundum type. Report of three families

The authors report on three Sicilian families with 17 individuals (10 females and 7 males) in successive generations affected by atrial septal defect of ostium secundum type (S-ASD) without conduction defect. The anomaly was inherited as an autosomal dominant trait. Cytoplasmic inheritance could be excluded, the anomaly being transmitted also by fathers. Familial S-ASD is probably more frequent than commonly reported since cardiological examination of the relatives is not routinely performed in every case of apparently sporadic ASD.     

Molecular signatures of cardiac defects in down syndrome lymphoblastoid cell lines suggest altered ciliome and hedgehog pathways

Forty percent of people with Down syndrome exhibit heart defects, most often an atrioventricular septal defect (AVSD) and less frequently a ventricular septal defect (VSD) or atrial septal defect (ASD). Lymphoblastoid cell lines (LCLs) were established from lymphocytes of individuals with trisomy 21, the chromosomal abnormality causing Down syndrome. Gene expression profiles generated from DNA microarrays of LCLs from individuals without heart defects (CHD(-); n?=?22) were compared with those of LCLs from patients with cardiac malformations (CHD(+); n?=?21). After quantile normalization, principal component analysis revealed that AVSD carriers could be distinguished from a combined group of ASD or VSD (ASD+VSD) carriers. From 9,758 expressed genes, we identified 889 and 1,016 genes differentially expressed between CHD(-) and AVSD and CHD(-) and ASD+VSD, respectively, with only 119 genes in common. A specific chromosomal enrichment was found in each group of affected genes. Among the differentially expressed genes, more than 65% are expressed in human or mouse fetal heart tissues (GEO dataset). Additional LCLs from new groups of AVSD and ASD+VSD patients were analyzed by quantitative PCR; observed expression ratios were similar to microarray results. Analysis of GO categories revealed enrichment of genes from pathways regulating clathrin-mediated endocytosis in patients with AVSD and of genes involved in semaphorin-plexin-driven cardiogenesis and the formation of cytoplasmic microtubules in patients with ASD-VSD. A pathway-oriented search revealed enrichment in the ciliome for both groups and a specific enrichment in Hedgehog and Jak-stat pathways among ASD+VSD patients. These genes or related pathways are therefore potentially involved in normal cardiogenesis as well as in cardiac malformations observed in individuals with trisomy 21.     

Transcatheter leadless permanent pacemaker in complex congenital heart disease with interrupted inferior vena cava: A challenging implantation

31 years lady with complete atrioventricular canal defect, large primum atrial septal defect (ASD), inlet ventricular septal defect (VSD) and Eisenmenger syndrome, presented with atrial flutter and complete heart block. She was not suitable for corrective cardiac surgery and not yet indicated for heart-lung transplantation. She was advised single chamber permanent pacemaker and eventually Micra VR transcatheter leadless pacemaker was finalised for her. Transcatheter leadless pacemaker was deployed in her RV septum despite some unforeseen technical problems. This patient had intrahepatic interruption of IVC with Azygous continuation draining into SVC but this altered venovascular course was detected only fluoroscopically midway during the pacemaker implantation procedure and this was not detected in the preprocedural transthoracic echocardiography. This abnormal venous course was clearly demonstrated in the cardiac CT which was performed only after completion of the pacemaker implantation procedure in this patient. The technical challenges encountered mainly were mostly during the manipulation of the 27F delivery catheter of Micra through this altered cardiovascular anatomy via transfemoral approach and also due to the presence of septal defects. Thus, transcatheter leadless permanent pacemaker was implanted successfully through transfemoral access in this complex congenital heart disease with interrupted IVC and azygous continuation. Besides transthoracic echocardiography, it may be better to perform transesophageal echocardiography or even preferably radiological imaging like cardiac CT or MRI prior to transcatheter leadless pacemaker implantation in patients with complex congenital heart disease to understand the cardiovascular anatomy and plan the procedure.     

Association of cleft lip and atrial septal defect in mice: a preliminary report.

Newborn A/J and CL/Fr mice with congenital cleft lip usually have an atrial septal defect of the secundum type, often associated with cyanosis. Their littermates without cleft lip rarely have a septal defect. The atrial septal defect results from a delay in growth of the atrial septum primum.     

SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects

In animal models of conotruncal heart defects, an abnormal calcium sensitivity of the contractile apparatus and a depressed L-type calcium current have been described. Sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) is a membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin (SLN), and all these proteins participate in maintaining the normal intracellular calcium handling. Ryanodine receptors (RyRs) are the major SR calcium-release channels required for excitation-contraction coupling in skeletal and cardiac muscle. Our objective was to evaluate SERCA2a (i.e., the SERCA cardiac isoform), PLN, SLN, and RyR2 (i.e., the RyR isoform enriched in the heart) gene expression in myocardial tissue of patients affected by tetralogy of Fallot (TOF), a conotruncal heart defect. The gene expression of target genes was assessed semiquantitatively by RT-PCR using the calsequestrin (CASQ, a housekeeping gene) RNA as internal standard in the atrial myocardium of 23 pediatric patients undergoing surgical correction of TOF, in 10 age-matched patients with ventricular septal defect (VSD) and in 13 age-matched children with atrial septal defect (ASD). We observed a significantly lower expression of PLN and SLN in TOF patients, while there was no difference between the expression of SERCA2a and RyR2 in TOF and VSD. These data suggest a complex mechanism aimed to enhance the intracellular Ca(2+) reserve in children affected by tetralogy of Fallot.     

Left ventricular assist device as a bridge to recovery in a young woman admitted with peripartum cardiomyopathy

Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure patients as a bridge to cardiac transplantation in those who deteriorate despite maximal therapy and when a donor heart is not ready available. In some patients, cardiac recovery has been reported while supported by an LVAD. In this case report, we describe a 29-year-old female who was admitted to our centre because of peripartum cardiomyopathy (PPCM). Despite intensive treatment with intravenous inotropes and intra-aortic balloon counter-pulsation she had a persisting low cardiac index and an LVAD was implanted. In the months following implantation the left ventricular systolic function improved and the left ventricular dimensions normalised. Eventually the LVAD could be ex-planted nine months after implantation. At this moment, three years after explantation, echo-cardiography shows a normal-sized left ventricle and almost completely recovered systolic function. (Neth Heart J 2008;16:426-8).     

Transcatheter device closure of atrial septal defects in patients aged 40 years and older

Objective. To evaluate the safety and effect of transcatheter device closure in ostium secundum atrial septal defects (ASD II) in patients aged 40 years and older.Methods. Retrospective single-centre study concerning 47 consecutive ASD transcatheter occlusion procedures performed between January 1999 and December 2008. Electrocardiography, echocardiography and clinical assessments of the patients were conducted pre- and post-intervention and at follow-up.Results. Of the 130 patients who were referred for interventional ASD closure, 47 were 40 years and older and all of them actually had the device inserted. There were no major complications during the intervention. Mean follow-up time was 15±15 months. During follow-up, three patients needed surgical reintervention because of device embolisation (n=2) or dislocation (n=1). Of the patients with severe right ventricular (RV) dilatation, more than half (58%) had no or mild dilatation at last follow-up. Reduction of RV dilatation was not related to age. Pulmonary hypertension was present in 63% before the procedure and was reduced to 38% at follow-up. NYHA class improved in all age groups, also in patients over 60 years of age. In two of the three patients who died during follow-up, no cause of death could be established, but both had responded well to treatment regarding the echocardiographic and clinical findings.Conclusion. Transcatheter device closure of ASD is a successful and effective treatment, also for patients aged 40 years and older. Patients showed regression of right ventricular enlargement and an improvement in functional class. (Neth Heart J 2010;18:537–42.)     

The aetiology of hypoxaemia in chickens selected for rapid growth

In comparison to other classes of chickens, broilers selected for rapid growth tend to be hypoxaemic, and many develop congestive heart failure (CHF). In order to explain the physiological mechanisms associated with hypoxaemia in fast-growing broiler chickens (Gallus gallus), this study examined several basic physiological parameters including the blood gas profile in arterial [left atrial (LA)] and mixed venous [right atrial (RA)] blood, systemic oxygen extraction ratio, and intrapulmonary shunt fraction. These parameters were further studied in the context of blood flow in the pulmonary circulation, structural characteristics of the lungs, and cardiac function [measured as cardiac index (CI)]. Overall, broilers had lower arterial and mixed venous blood pO(2) levels and higher pCO(2) levels compared to leghorns. The cardiac index was lower in fast-growing and CHF broilers compared to leghorn chickens or feed-restricted broilers. Systemic oxygen extraction ratio (ER) and intrapulmonary shunt fraction were significantly higher in fast-growing broilers and birds with CHF (all P<0.01). Lungs of all broilers, but not leghorns, contained ectopic, irregular nodular formations located within air spaces. Broilers with clinical signs of hypoxaemia revealed the highest number of these formations in their lung. Taken together, the present findings indicate that key factors associated with the development of hypoxaemia in fast-growing broilers include: (1) high demand for oxygen as evidenced by high oxygen ER; (2) inadequate cardiac output (CO) to fulfill the higher oxygen demands, leading to severe depletion of O(2) in mixed venous blood; and (3) elevated intrapulmonary shunt fraction and possibly dead space associated with specific pathological and anatomical characteristics within the lung.     

Atrial Septal Defect in Infancy

The case histories of seven infants with atrial septal defect are presented to draw attention to certain features and possible dangers of this defect in infancy. Four infants were asymptomatic but one failed to thrive and two died suddenly. Five had ejection murmurs and two, with pulmonary hypertension, had loud pan-systolic murmurs with a thrill. In two infants murmurs were noted at birth, but in five they were first heard between the ages of 1 and 6 months. The second pulmonary sound was initially narrowly split in all, but became widely split between the ages of 12 and 20 months. Electrocardiograms and chest roentgenograms were of little help at the outset but later showed findings characteristic of the defect after one year. All infants were catheterized; a left-to-right atrial shunt was detected in each instance. Pulmonary hypertension was present in two infants, one of whom died.     

Isolation,characterization and genetic analysis of canine <Emphasis Type="Italic">GATA4</Emphasis> gene in a family of Doberman Pinschers with an atrial septal defect

GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the third most common CHD in humans, it is generally rare in dogs and cats. There is also no obvious predilection for ASD in dogs and cats, based on sex or breed. However, among dogs, the incidence rate of ASD is relatively high in Samoyeds and Doberman Pinschers, where its inheritance and genetic aetiology are not well understood. In this study, we identified and investigated the genetic aetiology of an ASD affected family in a pure breed dog population. Although the GATA4 gene was screened, we did not find any mutations that would result in the alteration of the coding sequence and hence, the predicted GATA4 structure and function. Although the aetiology of ASD is multifactorial, our findings indicate that GATA4 may not be responsible for the ASD in the dogs used in this study. However, this does not eliminate GATA4 as a candidate for ASD in other dog breeds.