Immediate results of primary balloon dilation for congenital aortic valve stenosis predict the mid-term outcome.

BACKGROUND: Balloon valvuloplasty is the primary treatment for congenital aortic valve stenosis in our centre. We sought to determine independent predictors of reintervention (surgical repair or repeated balloon dilation) after primary valvuloplasty. METHODS: We retrospectively studied patients with congenital aortic valve stenosis who underwent balloon valvuloplasty during 2004-2018. The following risk factors were analysed: aortic valve insufficiency after balloon valvuloplasty >+1/4, post-procedural gradient across the aortic valve ≥35 mmHg, pre-interventional gradient across the valve, annulus size, use of rapid pacing, and balloon/annulus ratio. Primary outcome was aortic valve reintervention. RESULTS: In total, 99 patients (median age 4 years, range 1 day to 26 years) underwent balloon valvuloplasty for congenital aortic valve stenosis. After a mean follow-up of 4.0 years, 30% had reintervention. Adjusted risks for reintervention were significantly increased in patients with post-procedural aortic insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg (HR 2.55, 95% CI 1.13-5.75, p = 0.024). Pre-interventional gradient, annulus size, rapid pacing, and balloon/annulus ratio were not associated with outcome. CONCLUSION: Post-procedural aortic valve insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg in patients undergoing balloon valvuloplasty for congenital aortic valve stenosis confers an increased risk for reintervention in mid-term follow-up.

Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit.

Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region.Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.

Clinical and Hemodynamic Outcomes with Enalapril Orodispersible Minitablets in Young Children with Heart Failure Due to Congenital Heart Disease.

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06-0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07-0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms.

The role of modern imaging techniques in the diagnosis of malposition of the branch pulmonary arteries and possible association with microdeletion 22q11.2.

Malposition of the branch pulmonary arteries is a rare malformation with two forms. In the typical form, pulmonary arteries cross each other as they proceed to their respective lungs. The "lesser form" is characterised by the left pulmonary artery ostium lying directly superior to the ostium of the right pulmonary artery, without crossing of the branch pulmonary arteries. Malposition of the branch pulmonary arteries is often associated with other congenital heart defects and extracardiac anomalies, as well as with 22q11.2 microdeletion. We report three infants with crossed pulmonary arteries and one adolescent with "lesser form" of the malformation. The results suggest that diagnosis of malposition of the branch pulmonary arteries could be challenging if based solely on echocardiography, whereas modern imaging technologies such as contrast computed tomography and magnetic resonance angiography provide reliable establishment of diagnosis. In addition, we performed the first molecular characterisation of the 22q11.2 region among patients with malposition of the branch pulmonary arteries and revealed a 3-megabase deletion in two out of four patients

4q34.1-q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome.

UNLABELLED: Small terminal or interstitial deletions involving bands 4q34 and 4q35 have been described in several patients with a relatively mild phenotype such as mild to moderate intellectual disability and minor dysmorphic features. We present a boy born from unrelated parents with a de novo 4q34.1-q35.2 deletion and clinical features resembling 22q11.2 deletion syndrome. To the best of our knowledge, this is the first reported patient with 4q34-q35 deletion and phenotype resembling 22q11.2 deletion syndrome without fifth finger anomalies as a specific feature of 4q- syndrome. G-banding karyotyping disclosed the deletion, which was further delineated by microarray comparative genomic hybridization. Fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses did not reveal rearrangements of 22q11.2 region. MLPA confirmed the deletion within the 4q35.2 region. CONCLUSION: Given the considerable clinical overlaps between the 22q11.2 deletion syndrome and clinical manifestation of the patient described in this study, we propose that region 4q34.1-q35.2 should be considered as another region associated with phenotype resembling 22q11.2 deletion syndrome. We also propose that distal 4q deletions should be considered in the evaluation of patients with phenotypic manifestations resembling 22q11.2 deletion syndrome in whom no 22q11.2 microdeletion was detected, even in the absence of distinctive fifth finger anomalies. Additionally, we underline the importance of applying array CGH that enables simultaneous genome-wide detection and delineation of copy number changes (e.g., deletions and duplications).

Vomiting as the initial clinical presentation of myocardial infarction in children with anomalous left coronary artery from the pulmonary trunk.

Anomalous origin of the left coronary artery from the pulmonary trunk is a rare condition. The clinical presentation is usually nonspecific and varies from completely asymptomatic form to sudden cardiac death. We report a two-month-old infant with vomiting as a presenting symptom of anomalous origin of the left coronary artery from the pulmonary trunk.

Oral propranolol for infantile hemangiomas: a prospective study on the role of 48-hour Holter monitoring in additional safety assessment.

PURPOSE: Oral propranolol has been recently approved for infantile hemangiomas (IHs), but potential side effects stay a challenge. We sought to make an additional assessment on oral propranolol safety for this indication. MATERIALS AND METHODS: Prospective study included 108 infants consecutively treated for IHs at the University Children's Hospital Tirsova, Belgrade from January 2010 to December 2013. Propranolol was administered orally at a daily dose of 0.5 mg/kg and doubled every 48 hours in the absence of side effects until reaching the maximum dose of 2 mg/kg daily. Systolic and diastolic blood pressure and heart rate were measured every 48 hours with clinical observation. Heart rate was monitored by standard electrocardiogram (ECG) and 48-hour Holter ECG. RESULTS: Statistically significant, but asymptomatic decreases in systolic blood pressure and heart rate recorded by Holter ECG were observed during the first doubling of dose and then remained stable. Arrhythmias were not detected. Despite mild sleep disturbance observed in 31% of infants in the hospital milieu, Holter monitoring indicated circadian rhythm maintenance. CONCLUSIONS: Oral propranolol for IHs does not remarkably affect heart rhythm including circadian variations throughout hospital initiation. Therefore, there is no necessity for Holter monitoring in additional safety assessment.

[The Role of Two-Dimensional Echocardiography in Diagnostics of Coarctation of the Aorta in Newborns].

INTRODUCTION: Diagnosis of neonatal coarctation of the aorta (CoA) still presents a challenge in routine practice because of absence of reliable morphologic and functional parameters for early detection of this congenital heart defect in newborns. OBJECTIVE: The aim of this study is to identify easy obtainable two-dimensional echocardiographic parameters for detection of the CoA in newborns. METHODS: Echocardiographic evaluation was performed in 30 newborns with CoA and 20 healthy neonates (control group). Measurements of the proximal transverse arch (PTA), distal transverse arch (DTA), isthmus, distance between the left common carotid artery (LCCA) at the origin of the left subclavian artery (LSA), were obtained by two-dimensional echocardiography. Aortic arch hypoplasia was defined using Mouleart, Karl and Mee criteria, and Z-value. Index 1 was calculated as a ratio of DTA and distance between origins LCCA-LSA, Index 2 was calculated as a ratio of the ascending aorta and the distance between LCCA-LSA origins, and Index 3 was calculated as a ratio of PTA and distance between LCCA-LSA origins. RESULTS: Index 1 was significantly lower in patients with CoA in comparison with control group (0.50 vs. 1.39; p≤0.01). A cut-off point at 0.39, for Index 1, showed a sensitivity of 92% and specificity of 99% for the diagnosis of neonatal CoA, while cut off points at 0.69 and 0.44, for Index 2 and Index 3, showed the highest sensitivity and specificity for the diagnosis of CoA in newborns. CONCLUSION: By using these echo indexes, two-dimensional echocardiographic aortic arch measurement becomes a simple, reliable noninvasive method for the evaluation of aortic coarctation in newborns and may lead to earlier diagnosis and subsequent surgical correction.

[Outcomes of surgery for total anomalous pulmonary venous drainage].

INTRODUCTION: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease and in some variants represents the only true surgical emergency in congenital heart surgery. Basic anatomical characteristic of this anomaly is an abnormal connection of pulmonary veins with systemic venous circulation. Although the results of TAPVC repair in infancy have been markedly improved in recent years, the recurrent pulmonary venous obstruction (RPVO) remains relatively frequent complication of surgical treatment. OBJECTIVE: The aim of this study was a retrospective evaluation of TAPVC repair at a single institution, identifying the risk factors associated with the increased mortality and morbidity. METHODS: Between January 2001 and January 2010, 43 consecutive patients underwent repair of TAPVC at the University Children's Hospital, with median weight of 3.8 kg (1.8-13 kg). Median age at surgery varied from 5 days to 5 years. Distribution of TAPVC types was as follows: supracardiac 19 (44%), cardiac 12(28%), infracardiac 9 (21%), and mixed 3 (7%). Eleven patients (26%) were emergencies due to obstructed drainage. RESULTS: Early mortality was 9.30% (4/43). An average time of followup/survival for 95% interval of confidence was 101.6 +/- 6.7 months. Kaplan-Meier cumulative survival was 83.7 +/- 5.7%. Freedom from reintervention after 10 years was 87.2 +/- 0.5%. The principal reason for reintervention was RPVO. CONCLUSION: Preoperative obstruction is not a risk factor of early mortality and RPVO. Low body mass (below 2.5 kg) is the only identified risk factor of early mortality. Complex morphology of the confluens, particularly in a mixed type of TAPVR, is the main risk factor of RPVO development.

Balloon valvuloplasty as a treatment of congenital aortic stenosis in children and adolescents.

INTRODUCTION: Balloon valvuloplasty (BVP) is one of the primary therapies for congenital aortic stenosis in children and adolescents. The aim of this interventional procedure is to gain time before possible surgical therapy (aortic valve replacement) until adulthood. OBJECTIVE: The aim of this study was to evaluate the efficacy, safety and mid-term results oftranscatheter BVP in children and adolescent in our Center. METHODS: From 2004 to 2011, 50 patients, aged 18 days to 18 years (mean 6.3 years) underwent BVP. Retrospective analysis of the echocardiographic and hemodynamic parameters were performed before and after procedure, especially peak pressure gradient (PG) across the aortic valve, semiquantification of the aortic regurgitation (AR) after the BVP as well as the left ventricle dimensions and functions. RESULTS: The mean peak PG in the whole group decreased from 74.80 +/- 27.72 mm Hg to 27.86 +/- 3.04 mm Hg (p < 0.001) after BVP. In 39 patients (78%), residual PG was lower than 30 mm Hg just after dilation. At the end of follow-up period, 25 patients (50%) had PG above 50 mm Hg, measured by Doppler technique, and four of them underwent re-dilation. Eight patients (16%) had severe AR. During the follow-up period (12-80 months, mean 51 months), six patients (12%) were referred to cardiac surgeons for aortic valve replacement or Ross procedure. CONCLUSIONS: This retrospective study analyzes our first experience of BVP as primary therapy of the congenital aortic stenosis. The results confirmed that BVP effectively postponed the need for surgery in children and adolescents toward the adulthood.

Anomalous origin of the left coronary artery from the pulmonary artery, scimitar syndrome, and aortic coarctation.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) represents one of the most common causes of myocardial ischemia in infants and if left untreated results in a high mortality rate. When ALCAPA coexists with other congenital malformations, particularly those associated with pulmonary hypertension, the initial presentation can be quite confusing and is often misinterpreted. We report an infant with ALCAPA associated with scimitar syndrome and aortic coarctation whose clinical course illustrates the complexities and difficulties of management with a successful outcome.

[Mid-term results after complete surgical correction of transposition of the great arteries].

INTRODUCTION: Arterial switch operation (ASO) is a cardiosurgical method of choice for complete anatomical correction of transposition of great arteries. Improvement of this procedure has made considerably improved the outcome and long-term prognosis of children born with this complex congenital heart disease. OBJECTIVE: The aim of this study was to estimate the success rate of ASO through retrospective analysis of mortality and late complications. METHODS: This study included 57 children operated from 1st January 2005 until 31st December 2009. Parameters that could influence the outcome of surgery were investigated. The following late complications were investigated: neopulmonary artery stenosis, neoaortic stenosis and regurgitation, as well as clinical signs of heart failure. RESULTS: Early postoperative mortality was 15.8% (9/57 patients). During follow-up (8 to 72 months, average 36.5 months) there were no lethal outcomes. On the last echocardiography examination, 73.2% patients had neoaortic regurgitation and 67.4% patients had neopulmonary regurgitation, but all of them were mild in intensity. Neopulmonary stenosis had 32.6% of patients, but only two had moderate or severe stenosis. No one had ischemic ECG changes. Three reinterventions were performed due to serious residual problems: surgical correction of neoaortic stenosis, surgical correction of neopulmonary stenosis and transcatether balloon dilatation for aortic recoarctation. At the end of the follow-up period, only one of 46 consistently followed patients had signs of heart failure which required therapy (2.2%), while the majority of patients were without any symptoms and with good effort tolerance. CONCLUSION: Arterial switch operation has been successfully performed at our institution, with acceptable perioperative mortality and excellent late outcome.

Transcatheter stenting of arterial duct in duct-dependent congenital heart disease.

INTRODUCTION: Critical congenital heart diseases (CHD) are mostly duct-dependent and require stable systemic-pulmonary communication. In order to maintain patency of the ductus arteriosus (DA), the first line treatment is Prostaglandin E1 and the second step is the surgical creation of aortic-pulmonary shunt. To reduce surgical risk in neonates with the critical CHD, transcatheter stenting of DA can be performed in selected cases. CASE OUTLINE: A four-month old infant was diagnosed with the pulmonary artery atresia with ventricular septal defect (PAA/VSD). The left pulmonary artery was perfused from DA, and the right lung through three major aortopulmonary collaterals (MAPCAs). A coronary stent was placed in the long and critically stenotic DA, with final arterial duct diameter of 3.5 mm, and significantly increased blood supply to the left lung. After the procedure, the infant's status was improved with regard to arterial oxygen saturation, feeding and weight gain. During the follow-up, one year later, aortography revealed in-stent stenosis. The left pulmonary artery, as well as the branches, was well-developed and the decision was made to proceed with further surgical correction. CONCLUSION: Stenting of DA can be an effective alternative to primary surgical correction in selected patients with duct-dependent CHD.

Proteinuria in Frasier syndrome.

INTRODUCTION: Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms'tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure. CASE OUTLINE: We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria. CONCLUSION: RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.

Ruptured hydatid cyst of the interventricular septum with acute embolic pulmonary artery complications.

Hydatid cysts located in the interventricular septum are especially rare but with the high risk for intracavitary rupture. We report a patient with acute pulmonary embolism caused by an isolated, ruptured hydatid cyst on the right side of the interventricular septum. Early diagnosis was made by echocardiography and positive serology. Pulmonary artery embolism was confirmed by angiography and the patient was operated on. Embolectomy was performed by removing multiple fragments of ruptured endocyst from the left pulmonary artery, followed by surgical closure of a cyst cavity. Prompt diagnosis and an appropriate surgical treatment prevented a potentially fatal outcome.

[Early rehabilitation and cardiorespiratory response in children after correction of congenital heart defects].

INTRODUCTION: Significant improvement in survival and quality of life in patients after the correction of congenital heart defects was enabled by the introduction of surgical procedures. Due to increased vulnerability in the period after defect correction, early rehabilitation have found its place in recovery. Various studies suggest good effects of a rehabilitation programme especially in the early rehabilitation period. OBJECTIVE: In our study we wanted to stress the importance of early rehabilitation as well as its effects of implementation. METHOD: We evaluated the children treated at the University Children's Hospital during a four-year period. All participants were divided into two groups according to age: the first group included children up to the age of one year, and the second group included those from the first till the third year of life. Patients were divided into two groups according to the presence of complications. We monitored children with 4 types of congenital heart defects: Tetralogy of Fallot, Transposition of the Great Arteries, Coarctation of the Aorta and Stenosis of the Aorta. All exercises were implemented twice daily. Out of the pulmonary system parameters we monitored saturation of oxygen during the entire programme. Other parameters that were evaluated were: heart rate, ECG and breathing frequency. RESULTS: In the children with corrected defects, the most frequent complication was athelectasis especially in the group of patients till the first year of life. The patients with the onset of complications had a longer rehabilitation programme. Saturation of oxygen at the end of the programme was significantly elevated. CONCLUSION: From the above-mentioned it can be concluded that individual rehabilitation assessment for every patient is needed. Early rehabilitation measures give sustained effects of well-being after completion of the programme.

[Results of treatment of cyanotic heart defects in children]. / Rezultati lecenja cijanogenih mana srca kod dece.

Cyanotic heart diseases are relatively rare, but they are severe and heterogeneous congenital heart diseases, which require complex surgery. Development of different advanced surgical procedures, such as arterial switch operation (ASO), Fontan and its modifications, Norwood etc. operations, as well as better perioperative care significantly improved survival rate and quality of life of these children. The study group included 308 children treated for cyanotic heart disease in Yugoslavia, in the period January 2000 to July 2004. Some of them (239, 77.6%) were treated at the University Children's Hospital in Belgrade, and others (69, 22.4%) in different institutions abroad. The age of the operated patients varied between 1 day and 19 years (median 12 months). The patients (pts) were divided into four groups, according to the disease and type of the operation. In the whole group of 308 patients treated due to cyanotic heart disease, there were 232 (75.3%) cases with open heart surgery and 76 (24.7%) with closed procedures. The mortality rate was significantly different between disease/operation groups, and age groups. Average mortality rates differed from 11.8% for palliative procedures to 12.5% for complete corrections. Mortality rate and achieved surgical results in treatment of children with cyanotic heart diseases were significantly worse than those published by leading cardiac surgery centers in the world. However, there is a clear tendency in introducing new surgical procedures, lowering the age at which the operation is done and decreasing the mortality rates.