Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.

Background and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.

Antihypertensive therapy of late arterial hypertension in children following successful coarctation correction.

BACKGROUNG: Late arterial hypertension (AH) is the most significant complication of coarctation of the aorta (CoA). Only a few clinical studies described antihypertensive treatment of late AH following successful CoA repair. The primary objective of this multicentre cross-sectional study was to describe real-life antihypertensive therapy for late AH in children after hemodynamically successful CoA repair. The secondary objective was to describe antihypertensive therapy used within different haemodynamic phenotypes of AH. METHOD: Blood pressure status, echocardiographic parameters and central blood pressure measurements were evaluated in 110 children aged 6-18 years following successful CoA repair with right arm blood pressure not exceeding leg blood pressure by at least 20 mmHg. RESULTS: AH was found in 62 (56%) patients including 47 who were already treated and 15 with new diagnosed AH of whom seven presented with masked hypertension. Among treated patients, 10 presented with masked hypertension. The dominant phenotype of AH among patients with uncontrolled AH was isolated systolic hypertension (32 patients out of 37; 87.5%). AH was controlled in 53% of treated patients. Fifty-three percent of hypertensive patients had elevated central SBP and 39% had left ventricular hypertrophy with various left ventricle geometry patterns, 23% of them had both. ß-adrenergic receptor blockers were the most used antihypertensive drugs followed by angiotensin-converting enzyme inhibitors with doses within the lower recommended range. CONCLUSION: High prevalence of uncontrolled AH despite successful CoA repair and use of relatively low doses of antihypertensive drugs indicates the need of close blood pressure monitoring and more intensive and combined antihypertensive therapy.

Paediatric and adult congenital cardiology education and training in Europe.

BACKGROUND: Limited data exist on training of European paediatric and adult congenital cardiologists. METHODS: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. RESULTS: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41). CONCLUSION: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Multi-centre cross-sectional study on vascular remodelling in children following successful coarctation correction.

Coarctation of the aorta is an arteriopathy with life-long sequelae, with remarkably increased cardiovascular events in young adults even after successful repair and despite blood pressure status. There are data on arterial remodelling in adults after coarctation correction, however, these data are scarce in childhood. Thus, the aim of this cross-sectional study was to evaluate changes in arterial wall function and morphology in children following successful coarctation repair and to compare these changes among patients with different blood pressure status and coarctation correction modes. Blood pressure status, echocardiographic parameters, arterial wall structure and stiffness, endothelial function and central blood pressure measurements were evaluated in 110 children aged 6-18 years following successful coarctation repair with right arm blood pressure not exceeding leg blood pressure by ≥20 mmHg. The prevalence of arterial hypertension was 50%. The mean carotid intima-media thickness SDS was 3.1 ± 1.5 and above 1.65 SDS in 91 of 110 patients. Increased right carotid intima-media thickness was associated with left ventricular hypertrophy, office blood pressure difference between leg and right arm, recoarctation in the past and interventional coarctation correction. Increased local common carotid artery stiffness was associated with increased pulse pressure and central systolic blood pressure. Potentially decreased endothelial function was related to a slight increase of peak and mean systolic gradient in the descending aorta. After successful coarctation repair and with a low blood pressure gradient, children still have a high prevalence of arterial hypertension and significant arterial remodelling, indicating accelerated biological age and advanced arteriosclerosis.

Ebstein Anomaly and Right Aortic Arch in Patient with Charge Syndrome.

Ebstein anomaly is a rare congenital heart disease characterized by a varying degree of anatomical and functional abnormalities of tricuspid valve and right ventricle. It often coexists with other congenital cardiac malformations. Up to 79-89% of patients with Ebstein anomaly have interatrial communication in the form of patent oval foramen or atrial septal defect and more than one-third has other types of cardiac malformations. Association between Ebstein anomaly and right aortic arch is extremely rare and only few cases have been described in the literature so far. Much rarer than with other cardiac malformations, Ebstein anomaly is associated with non-cardiac malformations or genetic syndromes. Several cases of association between Ebstein anomaly and Charge syndrome have been reported, nevertheless, Ebstein anomaly accounts for less than 1% of cardiac defects seen in patients with Charge syndrome. In this case report, we present a unique case of a patient with Charge syndrome where both Ebstein anomaly and right aortic arch are present. The diagnosis of Ebstein anomaly and right aortic arch was established prenatally. In the first years of life, the patient did not exhibit any remarkable symptoms. However, over time, deterioration of right ventricle function and increased tricuspid regurgitation were observed, requiring consideration of surgical treatment at the age of five. In addition, delay in physical, motor, and mental development was observed and thus, at the age of five, the patient was consulted by a medical geneticist and a gene panel to test for structural heart defects was ordered. The test showed a mutation in chromodomain helicase DNA binding protein 7 (CHD7) gene, which, along with clinical features, allowed to establish a diagnosis of Charge syndrome. To the best of the authors' knowledge, this is the first case report of a patient with Charge syndrome, Ebstein anomaly, and right aortic arch that has been described in the literature.

Prevalence of arterial hypertension, hemodynamic phenotypes, and left ventricular hypertrophy in children after coarctation repair: a multicenter cross-sectional study.

BACKGROUND: This study aimed to evaluate hemodynamic phenotypes and prevalence of left ventricular hypertrophy in children after coarctation repair with right arm and leg blood pressure difference < 20 mmHg. Secondary objectives were analysis of effects of age at intervention, residual gradient across the descending aorta, and type of correction. METHODS: Blood pressure status and left ventricular hypertrophy were diagnosed according to European Society of Hypertension 2016 guidelines. RESULTS: Of 90 patients with a median age 12.5 (8.9-15.8) years, 8.5 (6.0-11.8) years after coarctation repair who were included, 42 (46.7%) were hypertensive. Isolated systolic hypertension dominated among 29 hypertensive patients with uncontrolled or masked hypertension (25 of 29; 86.2%). Of the 48 patients with office normotension, 14.6% (7) had masked hypertension, 8.3% (4) had ambulatory prehypertension, and 54.2% (26) were truly normotensive. Left ventricular hypertrophy was diagnosed in 29 patients (32.2%), including 14 of 42 (33.3%) hypertensive and 15 of 48 (31.3%) normotensive patients. The peak systolic gradient across the descending aorta was greater in hypertensive subjects (33.3 ± 12.7 mmHg) compared with normotensive subjects (25 ± 8.2 mmHg, p = 0.0008). Surgical correction was performed earlier than percutaneous intervention (p < 0.0001) and dominated in 40 of 48 (83.3%) normotensive versus 24 of 42 (57.1%) hypertensive patients (p = 0.006). CONCLUSIONS: Arterial hypertension with isolated systolic hypertension as the dominant phenotype and left ventricular hypertrophy are prevalent even after successful coarctation repair. Coarctation correction from the age of 9 years and older was associated with a higher prevalence of hypertension.

Initial experience with Edwards SAPIEN valve transcatheter implantation in native RVOT in Latvia.

Transcatheter pulmonary valve implantation has been a well-known method for more than a decade, but there are still many challenging cases when a personalized solution is needed. We report a case of a 15-year-old female patient with tetralogy of Fallot, who underwent a  surgical correction during infancy. Because of progressive pulmonary regurgitation, stenosis, and right ventricle dilatation, transcatheter pulmonary valve implantation in the native right ventricle outflow tract (RVOT) using Edwards SAPIEN valve was performed. A "landing zone" was created prior to the intervention of stenting the RVOT and the right pulmonary artery. The transcatheter approach for pulmonary valve replacement in a native RVOT is a reasonable alternative to the surgical approach.

A Giant Arteriovenous Malformation and Fistula in a Newborn with Parkes Weber Syndrome. Case Report.

Parkes Weber syndrome (PWS) is a rare congenital condition characterized by capillary cutaneous malformation, limb hypertrophy and multiple arteriovenous fistulas of the affected extremity. Another feature is a port-wine stain on the affected area. PWS is caused by genetic variations in the RAS p21 protein activator (RASA1) gene which affects the development of the vascular system. We report a case of a female neonate presenting with dyspnoea and cardiovascular insufficiency at the time of birth. The left upper extremity (LUE) and shoulder were enlarged (circumference at the midpoint was 17 cm compared to 11 cm on the right arm), edematous, hyperemic with a port-wine stain. Structural changes of the bones of LUE were discovered on X-ray. Echocardiography revealed right-sided volume overload, a large ductus arteriosus, a possible pathology of the aortic arch and branch arteries. Chest X-rays showed cardiomegaly. Therapy with milrinone and diuretics was started. A multislice CT angiography scan revealed arteriovenous fistula (AVF) between a. subclavia sin. and v. bra-chiocephalica sin, arteriovenous malformations (AVM) and a dilated a.subclavia sin. of 11 mm, as well as dilatation of other arteries of the LUE. Next generation sequencing revealed a pathogenic variation (c.2245C>T, p.Arg749*) in the RASA1 gene in the heterozygous state. Four consecutive embolizations of the AVM and AVF were performed in the first 16 months.

Incidence and Outcomes of Patients with Functionally Univentricular Heart Born in Latvia, 2007 to 2015.

Background and Objectives: A functionally univentricular heart is the term used to describe congenital heart defects where it is impossible to restore two pumping chambers. These lesions are associated with high mortality, morbidity, and medical resource utilization. The aim of this study was to review incidence and outcomes of patients with a functionally univentricular heart at the only pediatric cardiac surgery center in Latvia. Methods: We performed a retrospective review of medical records of (i) all children with a functionally univentricular heart treated at the Clinic of Pediatric Cardiology and Cardiac Surgery, and (ii) all prenatally diagnosed cases of univentricular heart at Children's Clinical University Hospital in Latvia. We reviewed data regarding children born from January 1, 2007, to December 31, 2015. The children's cardiac anatomy and interventions were categorized in accordance with the International Pediatric and Congenital Cardiac Code (v3.3). Results: During the study period, 49 patients with a functionally univentricular heart were admitted to Children's Clinical University Hospital with a corrected incidence of 0.69 per 1000 live births per year. There were 26 patients that had a hypoplastic left ventricle, and 22 patients that had a hypoplastic right ventricle, while one patient had an indeterminate ventricle. Thirty (61.2%) patients had died by the end of data collection. Twenty-one of the 30 deaths occurred before or immediately after stage I surgical palliation. Cumulative neonatal and 5-year survival of patients with a hypoplastic right ventricle was 81.8% and 63.6%, respectively; for patients with hypoplastic left ventricle-46.2% and 17.3%, respectively. Discussion: This is the first mid-term outcome study of patients with a univentricular heart in Latvia. The high mortality reflects the challenges of a small-volume, developing congenital cardiac surgery center. Data from this study will be used as a baseline for quality improvement.

Hypoplastic left heart syndrome: a review.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is an etiologically multifactorial congenital heart disease affecting one in 5,000 newborns. Thirty years ago there were no treatment options for this pathology and the natural course of the disease led to death, usually within the first weeks of life. Recently surgical palliative techniques have been developed allowing for a five-year survival in more than half the cases. MATERIALS AND METHODS: We reviewed literature available on HLHS, specifically its anatomy, embryology and pathophysiology, and treatment. The Pubmed and ClinicalKey databases were searched using the key words hypoplastic left heart syndrome, foetal aortic valvuloplasty, foetal septoplasty, Norwood procedure, bidirectional Glenn procedure, Fontan procedure, hybrid procedure. The relevant literature was reviewed and included in the article. We reported a case from Children's Clinical University Hospital, Riga, to illustrate treatment tactics in Latvia. RESULTS: There are three possible directions for therapy in newborns with HLHS: orthotopic heart transplantation, staged surgical palliation and palliative non-surgical treatment or comfort care. Another treatment mode - foetal therapy - has arisen. Staged palliation and full Fontan circulation is a temporary solution, however, the only means for survival until heart transplantation. Fifty to 70% of patients who have gone through all three stages of palliation live to the age of five years. CONCLUSIONS: The superior mode of treatment is not yet clear and the management must be based on each individual case, the experience of each clinic, as well as the financial aspects and will of the patient's parents.

Follow-up of the patients after stem cell transplantation for pediatric dilated cardiomyopathy.

Dilated cardiomyopathy is a serious problem in pediatric cardiology. Despite the relatively low incidence, the mortality is high. The conservative therapy does not improve the prognosis, and possibilities of heart transplantation are limited. There are multiple trials of use of stem cells for ischemic heart disease in the adult population. This allows us to believe that the method has perspectives in pediatric cardiology. We performed the cell therapy for seven patients, six of them had complete one yr follow-up after procedure. Five to 30 milliliters of bone marrow was aspirated from the iliac crest and 17 to 122 million BMCs were isolated. The average basal EF was 33.5%. We observed increasing of EF up to 54% (=9.54, p=0.00154) in a 6-month period and up to 54.5% (=10.82, p= 0.00315) after one yr. The changes of LVEDV also were observed. The LVEDV decreased in average per 13.05%. There were no observed side effects or heart rhythm disorders. Intramyocardial administration of bone marrow-derived progenitor cells proved to be a technically feasible and safe method. Up until now, the results obtained have been promising and we suppose that bone marrow-derived progenitor cell intramyocardial transplantation can be used.

Giant fibroma of the right ventricle.

Cardiac fibromas are rare benign tumours of connective tissue that occur most frequently in children within the left ventricle. Spontaneous regression has not been observed, and surgical intervention is usually required. We have successfully treated a 1-year old girl with a giant fibroma of the right ventricle using the principles of the Batista procedure. The diagnosis was primarily made using transthoracic echocardiography.