Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation.

Left ventricular non-compaction (cardiomyopathy) (LVN(C)) is a rare hereditary cardiac condition, resulting from abnormal embryonic myocardial development. While it mostly occurs as an isolated condition, association with other cardiovascular manifestations such as Ebstein anomaly (EA) has been reported. This congenital heart defect is characterized by downward displacement of the tricuspid valve and leads to diminished ventricular size and function. In an autosomal dominant LVN(C) family consisting of five affected individuals, of which two also presented with EA and three with mitral valve insufficiency, we pursued the genetic disease cause using whole exome sequencing (WES). WES revealed a missense variant (p.Leu113Val) in TPM1 segregating with the LVN(C) phenotype. TPM1 encodes α-tropomyosin, which is involved in myocardial contraction, as well as in stabilization of non-muscle cytoskeletal actin filaments. So far, LVN(C)-EA has predominantly been linked to pathogenic variants in MYH7. However, one sporadic LVN(C)-EA case with a de novo TPM1 variant has recently been described. We here report the first LVN(C)-EA family segregating a pathogenic TPM1 variant, further establishing the association between EA predisposition and TPM1-related LVN(C). Consequently, we recommend genetic testing for both MYH7 and TPM1 in patients or families in which LVN(C)/non-compaction and EA coincide.

Catheter interventions in congenital heart disease without regular catheterization laboratory equipment: the chain of hope experience in Rwanda.

This report describes the feasibility and safety of cardiac catheterization in a developing country without access to a regular cardiac catheterization laboratory. The equipment used for imaging consisted of a monoplane conventional C-arm X-ray system and a portable ultrasound machine using the usual guidewires and catheters for cardiovascular access. In this study, 30 patients, including 17 children younger than 2 years and 2 adults, underwent catheterization of the following cardiac anomalies: patent ductus arteriosus (20 patients) and pulmonary valve stenosis (9 patients, including 2 patients with critical stenosis and 3 patients with a secundum atrial septal defect). Except for two cases requiring surgery, the patients were treated successfully without complications. They all were discharged from hospital, usually the day after cardiac catheterization, and showed significant clinical improvement in the follow-up evaluation. Cardiac catheterization can be performed safely and very effectively in a country with limited resources. If patients are well selected, this mode of treatment is possible without the support of a sophisticated catheterization laboratory.

Closure of a lateral baffle leak in a Fontan patient with an amplatzer PDA II AS plug.

Cyanosis after Fontan surgery or surgery for total cavopulmonary connection (TCPC), due to different types of communications (fenestration, venovenous collaterals or fistula), is not uncommon. We present the case of an 8-year-old girl presenting with increasing cyanosis during exercise 4 years after an intracardiac TCPC with lateral tunnel. Angiography showed a fistulous trajectory originating at the superior vena cava towards the base of the right atrial appendage. Due to the difficult anatomy in our patient, closure with conventional devices was not possible. We finally used a new Amplatzer PDA II AS plug to successfully close the fistula. In conclusion, closure of lateral baffle leak and device choice in case of difficult anatomy can be cumbersome. The new PDA II AS type plug can offer an elegant alternative for successful closure of some fistula.

Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood.

INTRODUCTION: Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. METHODS: Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m² and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n = 19) or 240 mg/m² (n = 18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. RESULTS: No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. CONCLUSION AND IMPLICATIONS FOR CANCER SURVIVORS: At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m², no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients.

Pulmonary function in children after surgical and percutaneous closure of atrial septal defect.

This study aimed to study differences in lung function after surgical and percutaneous atrial septal defect (ASD) closure. Several studies have demonstrated abnormalities of pulmonary function in adults and children with ASD. These abnormalities persist even a few years after correction. This study compared pulmonary function between patients who underwent ASD closure by surgery and those who had closure by device. This is the ideal pediatric population for studying changes in lung function caused by cardiopulmonary bypass or sternotomy. The 46 patients in this study were treated by percutaneous closure (group 1) or surgical closure (group 2) of ASD and then scheduled for pulmonary function testing an average of 5.8 years after ASD closure. The mean values of functional residual capacity, total lung capacity, and residual volume did not differ between the two groups. The surgical group showed a significant decrease in expiratory reserve volume (p < 0.04) and forced vital capacity (p < 0.03). Expiratory flow at 25, 50, and 75% of forced vital capacity did not differ between the two groups but was on the lower limit of normal in both groups. Percutaneous closure of ASD can minimize the side effects of surgical closure on lung function. Longitudinal lung function follow-up assessment after cardiac surgery is warranted to detect and measure restrictive abnormalities in this type of congenital heart disease and others.

Effective cardioverter defibrillator implantation in children without thoracotomy: a valid alternative.

The implantation method for a cardioverter defibrillator in children is poorly standardized because of obvious features related to size and predisposing cardiac disease in children presenting with malignant ventricular arrhythmia. We propose an alternative method of implanting a cardioverter defibrillator without the need for associated thoracotomy, based on the subxiphoidal insertion of an epicardial bipolar ventricular pacing and sensing lead, an active can placed in the abdomen, and a subcutaneous array tunneled along the left thoracic wall as a shock electrode. This technique offers the advantage of an effective and minimally invasive implantable cardioverter defibrillator with wide applicability for children, independent of their size and cardiac status.

Plastic bronchitis in a 5-year-old boy causing asystoly and fatal outcome.

Here we present the case of a 5-year-old boy who experienced a prehospital cardiac arrest after a period of wheezing, upper respiratory tract infection, and diarrhea. After successful resuscitation, ventilation was initially extremely difficult for no obvious reason. Various bronchodilatatory therapies were started with only limited result. Diagnosis of plastic bronchitis was made after bronchoscopy and at autopsy when therapy was withdrawn in view of the absence of cerebral circulation. A thickened basal membrane, a specific hallmark of asthma, was also present. Cardiac arrest in plastic bronchitis due to inflammatory and allergic disease is very rare. Pathological examination of the cast showed a mucinous cast with neutrophilic granulocytes, which is also seldom seen. This case illustrates that the diagnosis of plastic bronchitis can be extremely difficult if only minor respiratory symptoms occur. This resulted in a delayed diagnosis and fatal outcome.

Transthoracic echocardiography guidance of transcatheter atrial septal defect closure in children.

Transesophageal echocardiography (TEE) guidance is part of interventional closure of secundum atrial septal defect (ASD) in children and adults. However, sometimes TEE is impossible for technical or anatomical reasons. If available, intracardiac echocardiography can be used, but especially in children, transthoracic echocardiography (TTE) can be an easy, safe, and cheap alternative. We report two cases in which TEE was replaced by TTE during percutaneous ASD closure. In the first case VACTERL association with a surgically repaired tracheoesophageal fistula was a relative contraindication to TEE. In the second case, technical failure of the transesophageal probe occurred during the procedure. In both cases the ASD was successfully closed with an atrial septal occluder device under TTE guidance. Using TTE can be sufficient and safe in children with good imaging windows, especially from subcostal views.

Pleural effusions, water balance mediators and the influence of lisinopril after completion Fontan procedures.

OBJECTIVE: To investigate whether the duration of pleural drainage after Fontan completion operations can be influenced by postoperative lisinopril administration or can be related to water balance hormone levels. METHODS: In a prospective trial 21 patients scheduled for total cavopulmonary connection were randomized into two groups, with group I receiving lisinopril postoperatively, and group II receiving no angiotensin converting enzyme inhibitor. Plasma levels of antidiuretic hormone, renin and aldosteron were analyzed preoperatively and at four-time points postoperatively. Groups were comparable for age, preoperative saturation and pulmonary pressure, cardiopulmonary bypass time, cross-clamp time and preoperative hormone levels. RESULTS: Mean duration of pleural drainage was comparable for both groups (group I: 9.6+/-8 days vs group II: 10+/-7 days; p=0.78). The hormone profiles in each group changed significantly at 1 and 24h postoperatively compared to preoperative values (p<0.05), with no significant differences between the treatment groups. The duration of pleural drainage correlated significantly with hormone levels at 24h postoperatively, and with longer bypass times. At multivariate analysis only aldosteron and antidiuretic hormone level at 24h came out as factors reaching significance for prolonged pleural drainage. CONCLUSIONS: The Fontan completion induces significant changes in the levels of antidiuretic hormone, aldosteron and renin. Prolonged drainage correlates significantly with elevated levels of aldosteron, renin and antidiuretic hormone postoperatively, and with longer bypass time, but is not influenced by lisinopril. The eventual adjunct therapy with aldosteron antagonists warrants further study.

Congenital heart disease in 111 225 births in Belgium: birth prevalence, treatment and survival in the 21st century.

AIM: To investigate the birth prevalence, treatment modalities and short-term survival of children with congenital heart disease who were born in 2002. METHODS: We undertook a retrospective review of medical records of all patients who were born in 2002, and were diagnosed, treated and/or followed-up in one of the seven-paediatric cardiology programmes in Belgium. RESULTS: In 111 225 births, 921 children with congenital heart disease were detected, yielding a birth prevalence of 8.3 per 1000. The most frequently occurring conditions were ventricular septal defects (VSDs) (33%), ostium secundum atrial septal defects (18%) and pulmonary valve abnormalities (10%). Thirty-nine percent of the children either had a cardiosurgical operation or catheter intervention. In this study, 4% of the children died. The actuarial survival at 6 months and 1 year of age was 97% and 96%, respectively and remained stable after then. Compared to other heart defects, mortality was higher in univentricular physiology, pulmonary atresia with VSD, left ventricle outflow obstruction and tetralogy of Fallot. CONCLUSION: Survival of congenital heart disease is excellent and continued to improve in the early 21st century. New therapeutic options are increasingly used. This study provides baseline data for the longitudinal follow-up of this cohort.

Unsuccessful resuscitation of a preterm infant due to a pneumothorax and a masked tension pneumopericardium.

Pneumopericardium is the least common form of air leak in infants. A tension pneumopericardium is even more infrequent but associated with a very high mortality rate. We describe the case of an unsuccessful resuscitation in a preterm infant due to a pneumothorax and tension pneumopericardium. Despite relatively mild pressure ventilation the patient developed massive pulmonary interstitial emphysema. The extra-alveolar air spread from the interstitium towards the mediastinal space (Macklin effect) and caused a pneumothorax and pneumopericardium, which evolved towards a tension pneumopericardium after a traumatic mechanical procedure. The infant deteriorated acutely. Despite prompt pleural drainage there were no signs of recovery at any time. Postmortal examination revealed a tension pneumopericardium and massive interstitial pulmonary emphysema, which was not obvious on radiographical investigation. In cases of acute deterioration of a ventilated neonate, one should always rule out pneumothorax. If the patient does not recover after pleural drainage and cardiac resuscitation a (tension) pneumopericardium should be considered.

Early cardiac abnormalities in obese children: importance of obesity per se versus associated cardiovascular risk factors.

We investigated whether obese children and adolescents have early echocardiographic signs of subclinical cardiac dysfunction and evaluated the respective influence of obesity per se versus parameters of carbohydrate and lipid metabolism that are frequently abnormal in obese subjects. The role of tissue Doppler imaging as a screening tool for these abnormalities was explored. Blood pressure and echocardiographic parameters, including tissue Doppler measurements of the septal mitral annulus were evaluated in 49 obese children and adolescents and 45 age and sex matched controls. The respective influence of obesity versus parameters of carbohydrate and lipid metabolism was examined with linear regression analysis. Obese subjects showed significantly larger left ventricular wall dimensions (posterior wall, septum, and left ventricular mass index) and signs of early diastolic filling abnormalities on conventional and tissue Doppler echocardiography compared with nonobese subjects. Multiple regression analysis showed that mainly BMI-SD scores and/or body surface area explained significant proportions of the variance of the early cardiac abnormalities. In conclusion, young, obese children and adolescents have significant changes in left ventricular wall dimensions and early diastolic filling compared with nonobese subjects. Obesity per se and not the parameters of carbohydrate and lipid metabolism predicted the early cardiac abnormalities.

Orthodeoxia-platypnea syndrome presenting as paradoxical peripheral embolism.

A paradoxical embolus associated with orthodeoxia-platypnea syndrome and intracardiac shunting is extremely uncommon. We present a patient who was found to have a positional change in desaturation after a right pneumonectomy who suffered from gangrene of the right foot and simultaneous deep venous thrombosis of the left arm. Workup revealed a patent foramen ovale as a cause for both the right-to-left shunt and the paradoxical emboli. After percutaneous closure the orthodeoxia resolved. This case highlights the necessity of heightened awareness of this syndrome in case of severe hypoxemia after pneumonectomy and the importance of an occult patent foramen ovale.

Midterm assessment of the reconstructed arteries after the arterial switch operation.

BACKGROUND: The arterial switch operation is the preferred treatment for transposition of the great arteries (TGA), but there are concerns on the fate of the neoarterial trunks. METHODS: Ninety-three children were reviewed for functional and morphologic assessment of both reconstructed arteries after the arterial switch operation. Longitudinal analysis focused on neoaortic valve function, neoaortic obstruction, and neopulmonary stenosis as well as on the time-related size changes of both roots, with its clinical implications. RESULTS: Within a mean follow-up of 4.8 +/- 3.9 years, aortic regurgitation of 2 or greater developed in 10% in TGA with intact ventricular septum (IVS) versus 23% in TGA with ventricular septal defect (VSD). A VSD and major pulmonary to aortic annulus size discrepancy were main precursors of early neoaortic valve dysfunction, whereas development of aortic regurgitation of 2 or greater was additionally promoted by the duration of follow-up. Presence of a VSD enhanced neoaortic root enlargement, resulting in a mean root z-score of 3.25 in TGA/VSD versus 1.96 in TGA/IVS. Root dilation was more severe in case of aortic regurgitation of 2 or greater (z = 3.38). Neoaortic obstruction occurred in 8%, mostly at the neosinotubular anastomosis, and correlated with prior pulmonary to aortic ratio greater than 1.5. Concerning the neopulmonary tract, increased flow velocity was observed in 24%, primarily at the supravalvular level. Two patients with pulmonary annulus hypoplasia (z < -2) required early reintervention. Regarding clinical outcome, freedom from reintervention at 1, 5, and 10 years was, respectively, 98%, 96%, and 96% for TGA/IVS, versus 65%, 63%, and 63% for TGA/VSD. A VSD and aortic arch obstruction were significant predictors for reintervention. CONCLUSIONS: After arterial switch operation, the neoaortic root is usually enlarged, but with a growth pattern comparable to that of a normal population. The association of a VSD and major arterial root size discrepancy predisposes to both neoaortic valve dysfunction and root enlargement. Severe root dilation appears to be closely related to significant neoaortic valve regurgitation, mainly as a result of a time-depending and reciprocal process. Neopulmonary stenosis is a frequent finding, but rarely has clinical consequences. Because the factor "time" is the principal determinant of late neoaortic valve dysfunction and root dilation, strict serial surveillance after arterial switch operation is mandatory.

Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase?

Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68+/-1.98 versus 7.92+/-1.60% in CO, p=0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008+/-224 versus 845+/-195 U/g Hb in CO, p=0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (>955 U/g Hb) had a significantly better FMD (p=0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.

Self-reported physical activities in patients after the Mustard or Senning operation: comparison with healthy control subjects.

BACKGROUND: Some decades ago, the Mustard or Senning operation was used to treat patients who were born with Transposition of the Great Arteries (TGA). Although life expectancy is good, previous studies have demonstrated limitations in exercise capacity. To what extent these limitations affect day-to-day functioning of the patients is not yet known. AIMS: We therefore investigated self-reported physical activities in patients after the Mustard or Senning operation, compared this with those of matched, healthy counterparts, and explored potential associations with age, gender and complexity of the TGA. METHODS: Seventy patients were matched with healthy controls. Habitual physical activity was measured using the Baecke questionnaire, resulting in a work, sports, and leisure time index, which ranges from 1 to 5. RESULTS: The median index scores of patients were 2.63 for work, 2.50 for sports; and 2.75 for leisure time. Only for sports, a significantly lower index score was found in patients. Furthermore, we found that older patients were less frequently engaged in sport activities (Spearman's rho=-0.38; p=0.02). CONCLUSION: The results showed that the level of physical activities of patients after the Mustard and Senning operation is normal, except for sport activities. This indicates that patients after a Mustard or Senning operation tend to partake in all activities that they can comfortably perform.

Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution.

AIMS: To determine the prevalence of sleep-disordered breathing (SDB) in a clinical sample of overweight and obese children and adolescents, and to examine the contribution of fat distribution. METHODS: Consecutive subjects without chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or craniofacial syndrome were recruited. All underwent measurements of neck and waist circumference, waist-to-hip ratio, % fat mass and polysomnography. Obstructive apnoea index > or =1 or obstructive apnoea-hypopnoea index (OAHI) > or =2, further classified as mild (2< or =OAHI<5) or moderate-to-severe (OAHI> or =5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas > or =10 s were present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation < or =85% after central events of any duration were also diagnosed with central sleep apnoea. Primary snoring was diagnosed when: snoring was detected by microphone and normal obstructive indices and saturation. RESULTS: 27 overweight and 64 obese subjects were included (40 boys; mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children, 53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to-severe OSA and 17% had central sleep apnoea. Half of the patients with central sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and fat mass were associated with central sleep apnoea. CONCLUSION: SDB is very common in this clinical sample of overweight children. OSA is not associated with abdominal obesity. On the contrary, higher levels of abdominal obesity and fat mass are associated with central sleep apnoea.