Complex Heart Defects Research Articles

Preoperative Extracorporeal Membrane Oxygenation as a Bridge to Cardiac Surgery in Children With Congenital Heart Disease

The efficacy of extracorporeal membrane oxygenation (ECMO) in bridging children with unrepaired heart defects to a definitive or palliative surgical procedure has been rarely reported. The goal of this study is to report our institutional experience with ECMO used to provide preoperative stabilization after acute cardiac or respiratory failure in patients with congenital heart disease before cardiac surgery. A retrospective review of the ECMO database at Children's Hospital Boston was undertaken. Children with unrepaired congenital heart disease supported with ECMO for acute cardiac or respiratory failure as bridge to a definitive or palliative cardiac surgical procedure were identified. Data collection included patient demographics, indication for ECMO, details regarding ECMO course and complications, and survival to hospital discharge. Twenty-six patients (18 male, 8 female) with congenital heart disease were bridged to surgical palliation or anatomic repair with ECMO. Median age and weight at ECMO cannulation were, respectively, 0.12 months (range, 0 to 193) and 4 kg (range, 1.8 to 67 kg). Sixteen patients (62%) survived to hospital discharge. Variables associated with mortality included inability to decannulate from ECMO after surgery (p = 0.02) and longer total duration of ECMO (p = 0.02). No difference in outcomes was found between patients with single and biventricular anatomy. Extracorporeal membrane oxygenation, used as a bridge to surgery, represents a useful modality to rescue patients with failing circulation and unrepaired complex heart defects.

Anomalous Left Anterior Descending Coronary Artery from the Pulmonary Artery, Unroofed Coronary Sinus, Patent Foramen Ovale, and a Persistent Left-sided SVC in a Single Patient: A Harmonious Quartet of Defects

Unroofing of the coronary sinus without complex structural heart defects is a rare congenital defect often seen in conjunction with a persistent left-sided superior vena cava. Anomalous origin of the left anterior descending artery from the pulmonary artery with normal origin of the left circumflex coronary artery is an even rarer congenital cardiac defect. We report a case of a 54-year-old woman presenting with mild dyspnea on exertion who was found on invasive and noninvasive evaluations to have a unique combination of defects—unroofed coronary sinus, persistent left-sided superior vena cava, patent foramen ovale, and anomalous origin of the left anterior descending artery from the pulmonary artery without evidence of previous coronary ischemia.

‘Big‐eyed frog’ sign on spatiotemporal image correlation (STIC) in the antenatal diagnosis of transposition of the great arteries

To determine the value of simultaneous visualization of the cross-sectional view of both atrioventricular (AV) valves, the pulmonary artery and the aorta (en-face view of the AV valves and great vessels) in the identification of fetuses with transposition of the great arteries (TGA). This was a retrospective analysis of volume datasets obtained with the spatiotemporal image correlation (STIC) technique from 56 fetuses with and 30 fetuses without congenital heart defects. Volume datasets were reviewed offline to compare the en-face view of the AV valves and great vessels between fetuses with normal echocardiography and those with TGA. The en-face view of both AV valves and great vessels in fetuses with TGA displayed the main pulmonary artery situated side-by-side with the aorta ('big-eyed frog' sign). In contrast, fetuses with normal hearts did not have this characteristic sonographic sign. This novel sonographic sign also helped to identify additional cases of TGA in 17 fetuses with complex heart defects. The big-eyed frog sign may prove helpful in the prenatal diagnosis of TGA.

Initial Development of the Pediatric Camp Outcome Measure

The objective of this pilot study was to develop the Pediatric Camp Outcome Measure (PCOM), an instrument designed to assess children's perception of the pediatric camp experience. Fifty-one children completed the PCOM at the end of a 1-week pediatric summer camp for individuals with complex heart defects. Participants also completed measures of anxiety, depression, and quality of life to provide support for the dimensions measured in the PCOM. The resultant 27-item, multidimensional instrument demonstrated strong internal consistency estimates for the total scale (α = .93) and each subscale (self-esteem, α = .84; emotional functioning, α = .84; socialization, α = .89; physical activity, α = .80). Initial support for the utility of the PCOM and the subscales was provided by significant correlations with concurrent measures of depression, anxiety, and general and cardiac-related quality of life. This study provides initial data and support for the use of the PCOM to measure children's responses to pediatric specialty camps.

Right ventricular outflow tract reconstruction with valved bovine jugular vein conduit

Objectives: Management for the repair of many congenital complex heart defects may require the implantation of a valved conduit into the right ventricular outflow-tract (RVOT). The Venpro ContegraTM conduit (CVC) is a bovine jugular vein graft, bearing a tri-leaflet venous valve. The aim of this study is to evaluate the short- and medium-term follow-up after implantation. Methods: 5/2000–8/2006: 14 patients (mean age 3.6 years, range 1 month to 9 years), of mean body weight 14.2kg (range 3.4–39.0kg) were operated using a CVC (12–20mm). Nine patients underwent primary repair and five had other previous operations. Mean follow-up: 46 months (14–81 months). Results: There were no hospital deaths. All RVOT reconstructions could be performed without any additional material, utilizing the surplus tissue on both ends of the CVC graft. At 12 months follow-up time all patients were in good clinical condition. However, one patient underwent balloon dilatation 11 months after operation. Freedom from reoperation and intervention at 1 year is 92,9%. Two patients required conduit exchange - 1.- endocarditis with vegetations two years after implantation and 2.- after 26 months, a 12mm CVC graft caused stenosis with gradient 64mmHg – which was replaced with a pulmonary homograft. All other conduits perform well. We have not observed thrombosis or thromboembolism. Conclusions: The readily available Contegra conduit seems to be a suitable alternative to homografts for RVOT-reconstruction in infants and young children. Of special appeal are its pliability and excellent handling-qualities.

Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder associated with ciliary defects and situs inversus totalis, the complete mirror image reversal of internal organ situs (positioning). A variable incidence of heterotaxy, or irregular organ situs, also has been reported in PCD patients, but it is not known whether this is elicited by the PCD-causing genetic lesion. We studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene commonly mutated in PCD. Analysis of homozygous mutant embryos from 18 litters yielded 25% with normal organ situs, 35% with situs inversus totalis, and 40% with heterotaxy. Embryos with heterotaxy had complex structural heart defects that included discordant atrioventricular and ventricular outflow situs and atrial/pulmonary isomerisms. Variable combinations of a distinct set of cardiovascular anomalies were observed, including superior-inferior ventricles, great artery alignment defects, and interrupted inferior vena cava with azygos continuation. The surprisingly high incidence of heterotaxy led us to evaluate the diagnosis of PCD. PCD was confirmed by EM, which revealed missing outer dynein arms in the respiratory cilia. Ciliary dyskinesia was observed by videomicroscopy. These findings show that Dnahc5 is required for the specification of left-right asymmetry and suggest that the PCD-causing Dnahc5 mutation may also be associated with heterotaxy.

Das zyanotische Kind mit kardialer Erkrankung im Notfalldienst

In contrast to the adult population with predominant pulmonary disease like chronic obstructive lung disease, a central cyanosis in the pediatric population is mainly caused by a congenital heart defect. The incidence of cyanotic congenital heart defects is about 13 per 10000 live births. Due to the fact, that nowadays even complex heart defects are successfully palliated, the chance to come across a child with central cyanosis in the emergency setting rises steadily. Reasons for the desaturated blood in the great arteries can either be a reduced lung perfusion or an increased mixture of arterial and venous blood due to a right-to-left shunt. The best indicator to detect a central cyanosis is the tongue since it has a rich vascular supply and is free of pigmentation. Depending on the child’s age, the essential primary rescue therapy is either the application of volume or high oxygen. In other cases no rescue therapy is required. After the preclinical rescue therapy, the child should always be admitted to a hospital, preferably to a pediatric intensive care unit or pediatric cardiology.

Familial CHARGE syndrome because of CHD7 mutation: clinical intra‐ and interfamilial variability

CHARGE syndrome (OMIM #214800) is a multiple malformation syndrome with distinctive diagnostic criteria, usually because of CHD7 (chromodomain helicase DNA binding 7) haploinsufficiency. Familial occurrence of CHARGE syndrome is rare. We report six patients from two Caucasian families (both with one parent and two children) affected by mild to severe CHARGE syndrome. Direct sequencing of the CHD7 gene was performed in these two unrelated families. A mutation in exon 8 (c.2501C>T - p.S834F) in first chromodomain was found in family A and a nonsense mutation in exon 2 (c.469C>T - p.R157X) in family B. Both mutations are de novo in the parents. In family A, the elder son had bilateral cleft lip and palate, esophageal atresia with fistula, complex heart defect and vertebral abnormalities, while the younger had a posterior coloboma. Their mother had asymptomatic vestibular dysfunction and retinal coloboma, identified after the molecular diagnosis of her children. In family B, both affected children had severe expression of CHARGE syndrome. The father carrying the mutation only had asymmetric anomaly of the pinnae. These familial reports describe the intrafamilial variability of CHARGE syndrome, and underline the presence of CHD7 mutations in patients who do not fit the 'classical clinical criteria' for CHARGE syndrome.

Elucidation of penetrance variability of aZIC3mutation in a family with complex heart defects and functional analysis ofZIC3mutations in the first zinc finger domain

We studied a series of 42 cases of transposition of the great arteries (TGA), a complex heart defect (CHD) that is two times more prevalent in males than in females. A mutation in the X chromosome at the ZIC3 gene was found in two affected siblings (one male, one female) and their unaffected mother. A second factor, skewed X-inactivation pattern explained the discrepancy between the daughter/mother phenotype. In this family, the missense mutation (p.W255G) was found in the first zinc finger of ZIC3, a domain that is relatively specific to each of the five human ZIC genes. It was tested further along with two other mutations of this domain (p.C253S and p.H286R). In transfected 3T3 cells, mutants p.W255G and p.H286R expressed lower protein levels, and an increased protein degradation (p.W255G only). Moreover, mutants p.C253S and p.W255G had a decreased transcription activation of the TK-luciferase reporter gene. Nuclear translocation of the three ZIC3 mutants varied considerably depending on the experimental models. Finally, p.W255G and p.H286R showed diminished activities for both left-right axis disturbance and neural crest induction in Xenopus embryos. These results suggest that mutations in the first zinc finger of ZIC3 mildly affect several functions of the protein.

Remote Control of Pulmonary Blood Flow

Pulmonary artery banding is a suitable approach for complex heart defects suitable to later bi-ventricular repair, functionally uni-ventricular hearts, and left ventricular retraining. Despite the existence of a very large spectrum of congenital heart defects and clinical situations with potential indication for pulmonary artery banding, the availability of only the conventional surgical technique is still limiting the application of this approach. A solution to the clinical need for an adjustable pulmonary artery banding has been found with a telemetrically controlled adjustable pulmonary artery banding, FloWatch® (EndoArt, Lausanne, Switzerland). This new implantable, wireless, bat-tery free, device (FloWatch®), demonstrated the feasibility of repeated progressive occlusions and re-openings of the de-vice at the wanted percentage of occlusion through a remote control, with long-term experimental evaluation in animals, followed by successful introduction in clinical practice in different institutions. The availability of a reliable adjustable pulmonary artery banding, avoiding any re-operation and the need for pulmonary artery reconstruction at the moment of de-banding, has substantially modified the clinical management of infants with congenital heart defects with increased pulmonary artery blood flow and pressures. New therapeutic strategies can now be considered to expand the applicability of this device. Keywords: Congenital heart defects, left-to-right shunts, pediatric cardiac surgery, pulmonary artery banding, pulmonary blood flow, pulmonary hypertension

Significance of Peritoneal Fluid Drainage in Management After Repair of Complex Heart Defects in Infancy Cytokine Dynamics In Vivo

In vivo redundancy of pro-inflammatory cytokines results in a vicious cycle of systemic inflammatory response syndrome and low cardiac output syndrome (LOS). The purpose of this study was to elucidate the influence of peritoneal fluid (PF) drainage on cytokine dynamics in vivo and the significance of early induction for infants with LOS. Seven infants, who underwent early PF drainage to manage LOS after repair of complex heart defects under cardiopulmonary bypass, were enrolled. The serum and PF levels of the pro- and antiinflammatory cytokines, interleukin (IL)-6, -8, -10 and tumor necrosis factor (TNF)-alpha, were measured during the perioperative period. Clinical outcomes were observed simultaneously. There were no cases of early or late death, or infectious complications. Drainage volume of PF peaked just after operation, and decreased completely. The amount of proinflammatory cytokines in the PF increased for 3 days after operation. Of the proinflammatory cytokines in the PF IL-6 increased the earliest and cleared the fastest. The amount of cleared IL-8 and TNF-alpha peaked on the 3rd postoperative day and resembled the course of C-reactive protein (CRP). Serum levels of CRP and proinflammatory cytokines in patients with PF drainage decreased significantly more than those without PF drainage. Early initiation of PF drainage is useful in the postoperative critical care of infants with LOS by improving cytokine dynamics in vivo, although there are differences between the severity of patients undergoing PF drainage and those who do not.

Outcome for Fetuses with Prenatally Detected Congenital Heart Disease and Cardiac Arrhythmias in Taiwan

Outcome for fetuses with prenatally detected congenital heart disease (CHD) and/or cardiac arrhythmias is important for prenatal counseling and perinatal management; however, there exists little literature regarding the outcome for CHD diagnosed in utero in Taiwan. Therefore, we attempted to investigate the outcome for fetuses with CHD and/or cardiac arrhythmias diagnosed prenatally at a tertiary care medical center in Taiwan. Between January 1995 and December 2000, 339 patients referred to the National Taiwan University Hospital for fetal echocardiography were included in this study. Medical records were reviewed retrospectively to determine the salient clinical characteristics for all fetuses. CHD was found in 103 fetuses. Gestational age at diagnosis ranged from 17 to 40 weeks; in 37 cases (35.9%) the diagnosis was made before 24 weeks. Mean gestational age at diagnosis was 27.8 weeks. Of the 103 cases, 15 fetuses (14.6%) had major extra cardiac malformations and 15 fetuses (14.6%) had chromosomal abnormalities (five had both) and 30 pregnancies (29.1%) were terminated. Of the remaining 73 pregnancies, three (4.1%) of the fetuses died in utero and 28 (38.4%) postnatally, with 42 (57.5%) surviving. The mortality rates were both 60% in cases with extracardiac or chromosomal anomalies. Arrhythmias were identified in 25, and two pregnancies involving hydrops fetalis were terminated. Of the remaining 23 continued pregnancies, two (8.7%) with long QT syndrome expired postnatally. Outcome for fetuses with prenatally detected CHD remains poor, with the prognosis negatively influenced by the presence of complex heart defects as well as extracardiac and chromosomal anomalies. However, prognosis is good for fetuses with cardiac arrhythmia, except with long QT syndrome or hydrops fetalis.

Duplication of (12)(pter-q13.3) combined with deletion of (22)(pter-q11.2) in a patient with features of both chromosome aberrations

We report a patient with multiple dysmorphic signs and congenital malformations, representing a combination of clinical features of duplication (12p) and deletion (22)(q11.2) syndromes. The girl had overgrowth at birth, showed abnormal cranio-facial findings, cleft uvula, a complex conotruncal heart defect, a polycystic right kidney, and an umbilical hernia. She died at the age of 6 months of cardio-respiratory failure. Cytogenetic examination demonstrated a derivative chromosome 12 replacing one of the two chromosomes 22. The paternal karyotype was normal 46,XY while the mother's karyotype was 46,XX,rcp(12;22)(q13.2;q11.2). According to the published data, all patients with deletion 22q11.2 combined with other unbalanced chromosomal aberration have a more severe clinical expression than those with interstitial deletions.

Mice with mutations in Mahogunin ring finger‐1 (Mgrn1) exhibit abnormal patterning of the left–right axis

Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left-right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20-25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46-60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis.

Coagulopathy and Inflammation in Neonatal Heart Surgery: Mechanisms and Strategies

Open cardiac surgery has enjoyed significant improvement in outcome during the last several years. Complex heart defects once considered fatal are now readily addressed with low mortality. However, repair of these defects requires the use of cardiopulmonary bypass (CPB), which results in significant alteration of normal homeostatic mechanisms. Normal hemostasis reflects a highly complex interaction between endothelial cells, platelets, local and systemic inflammatory mediators, and coagulation factors [1, 2].

Asplenia syndrome in a pair of monozygotic twins

AbstractAsplenia syndrome is one of the heterotaxy syndromes, which many familial and animal studies suggest are caused by the loss of adequate genetic control of normal left–right asymmetry development. Moreover, there has not been any environmental factor documented to cause these syndromes. Asplenia syndrome occurring in a pair of monozygotic twins is reported. In view of the negative family history, a new germline mutant gene might be the aetiology of our patients. Both twins are associated with some degree of discordant complex heart defects within the context of a high degree of “mirror‐image” of the unpaired thoracoabdominal organs. Conclusion: This report implies that sporadic asplenia syndrome might associate with new mutations and further genetic study may be indicated. These monozygotic twins' discordant phenotypes imply that some unidentified factors play an important role in their ultimate development of the same genetically determined abnormalities.

Asplenia syndrome in a pair of monozygotic twins

Asplenia syndrome is one of the heterotaxy syndromes, which many familial and animal studies suggest are caused by the loss of adequate genetic control of normal left-right asymmetry development. Moreover, there has not been any environmental factor documented to cause these syndromes. Asplenia syndrome occurring in a pair of monozygotic twins is reported. In view of the negative family history, a new germline mutant gene might be the aetiology of our patients. Both twins are associated with some degree of discordant complex heart defects within the context of a high degree of "mirror-image" of the unpaired thoracoabdominal organs. This report implies that sporadic asplenia syndrome might associate with new mutations and further genetic study may be indicated. These monozygotic twins' discordant phenotypes imply that some unidentified factors play an important role in their ultimate development of the same genetically determined abnormalities.

Postoperative Chylothorax: Differences Between Patients Who Received Median Sternotomy or Lateral Thoracotomy for Congenital Heart Disease

Chylothorax after surgery for congenital heart disease is rare. We wanted to compare the different presentations of chylothorax in patients who received median sternotomy or lateral thoracotomy. We retrospectively studied pediatric patients with congenital heart disease who received palliative or corrective surgeries and developed postoperative chylothorax between January 1992 and July 2003. Patients were divided into two groups by the type of surgery: median sternotomy and lateral thoracotomy. The average daily fluid amount (mL/kg/24 hours), latency period, duration of chylothorax, and requirement for surgery were compared. Seventeen patients (11 boys, 6 girls; mean age, 14.0 +/- 12.8-month-old) were enrolled. Diagnoses were tetralogy of Fallot (n = 8), right isomerism with complex heart defects (n = 3), patent ductus arteriosus (n = 2), transposition of the great artery (n = 1), ventricular septal defect (n = 1), and endocardial cushion defect (n = 2). There were 9 in the lateral thoracotomy group and 8 in the median sternotomy group. Only one patient required surgery because of the failure of conservative treatment. The lateral thoracotomy group had a significantly lower average body weight (6.9 +/- 2.9 kg vs. 11.0 +/- 3.8 kg) and longer average latency period before postoperative chylothorax (15.1 +/- 9.2 days vs. 7.2 +/- 4.7 days). The majority of pediatric patients who develop chylothorax after cardiac surgery can be successfully managed by medical treatment only. To avoid complications in pediatric patients after cardiac surgery, chylothorax should be suspected for patients with unexplainable, prolonged, and abundant pleural effusion.

Three-dimensional imaging of the fetal heart: Current applications and future directions

During the past 25 years fetal echocardiography has evolved from a research tool to a clinical tool used by obstetricians, maternal–fetal medicine specialists, radiologists, and pediatric cardiologists. Each group of physicians faces different tasks. The non-pediatric cardiologist is primarily involved with screening for heart defects in low-risk patients while the pediatric cardiologist is charged with the delineation of complex fetal heart defects. Both tasks can be challenging. With the introduction of 3D and 4D fetal echocardiography, a number of modalities are available to assist the non-cardiologist when performing the screening examination of the fetal heart that includes evaluation of the four-chamber and the outflow tract views of the fetal heart. These include the “spin” technique and the evaluation of tomographic imaging planes. Using similar techniques the pediatric cardiologist can render 3D and 4D views of the heart that are equivalent to anatomical models of the heart, as well as examine 2D image planes derived from 3D and 4D datasets that assist in identifying the nine image planes that have been defined for fetal echocardiography.

Cor triatriatum sinistrum

Cor triatriatum sinistrum (CTs) represents approximately 0.1% of congenital heart disease. The presence of an abnormal, often fenestrated fibromuscular membrane is indicative of CTs and results in a subdivided left atrium that can obstruct pulmonary venous return leading to elevated pulmonary venous and pulmonary artery pressures. We describe a case of CTs presenting well into adulthood with the unusual association of atrial flutter. Given the rarity of CTs, this unique observation with atrial flutter is limited to this case report, but is meant to illustrate the ramifications of this arrhythmia even in this relatively simple congenital heart defect, as our patient's arrhythmia was refractory to treatment and behaved similarly to atrial flutter observed among patients with more complex heart defects. Accurate diagnosis of the abnormal atrial membrane in the setting of other cardiac defects is imperative because pulmonary venous obstruction can occur after surgery for the associated defects. An associated atrial arrhythmia complicates management further and remains an important cause of morbidity and mortality in patients with congenital heart defects regardless of whether or not they have had corrective heart surgery. Atrial flutter is particularly worrisome since its onset is usually associated with clinical deterioration in adult patients with congenital heart defects. Physicians need to be cognizant of this increasing new cardiac patient population particularly after the typical causes of atrial flutter (e.g., ischemic disease, electrolyte disturbances, thyroid disease, and mitral valve disease, etc) have been ruled out.