Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.

In a consanguineous Pakistani family with two affected individuals, a homozygous variant Gly399Val in the eighth transmembrane domain of the taurine transporter SLC6A6 was identified resulting in a hypomorph transporting capacity of ~15% compared with normal. Three-dimensional modeling of this variant has indicated that it likely causes displacement of the Tyr138 (TM3) side chain, important for transport of taurine. The affected individuals presented with rapidly progressive childhood retinal degeneration, cardiomyopathy and almost undetectable plasma taurine levels. Oral taurine supplementation of 100 mg/kg/day resulted in maintenance of normal blood taurine levels. Following approval by the ethics committee, a long-term supplementation treatment was introduced. Remarkably, after 24-months, the cardiomyopathy was corrected in both affected siblings, and in the 6-years-old, the retinal degeneration was arrested, and the vision was clinically improved. Similar therapeutic approaches could be employed in Mendelian phenotypes caused by the dysfunction of the hundreds of other molecular transporters.

Outcome of paediatric portopulmonary hypertension in the modern management era: A case report of 6 patients.

Portopulmonary hypertension is a rare but serious complication of portal hypertension or portosystemic shunting. Portopulmonary hypertension is an indication for liver transplantation or shunt closure. However, liver transplantation is contraindicated in patients with severe pulmonary arterial hypertension. Reported mortality rates are high in children with portopulmonary hypertension and there are scarce recommendations on its management. Our aim was to report on our real-world experience of managing portopulmonary hypertension in a specialised centre. We describe a series of 6 children with portopulmonary hypertension. Their median age at diagnosis was 13 years (range 10-15). The underlying liver conditions were cirrhosis of unknown origin (1), congenital portocaval shunts (3), biliary atresia (1), and portal vein cavernoma with surgical mesenterico-caval shunt (1). Median mean pulmonary arterial pressure was 47 mmHg (range 32-70), and median pulmonary vascular resistance was 6.6 Wood units (range 4.3-15.4). All patients except one were treated with a combination of pulmonary arterial hypertension-specific therapy (phosphodiesterase type 5 inhibitors and/or endothelin receptor antagonists and/or prostacyclin analogues). Three patients then benefited from shunt closure and the others underwent liver transplantation. Five patients showed improvement or stabilisation of pulmonary arterial hypertension with no deaths after a mean follow-up of 39 months. Based on our limited experience, early and aggressive treatment with a combination of pulmonary arterial hypertension-specific therapy significantly improves patients' haemodynamic profile and enables the performance of liver transplantation and shunt closure with satisfactory outcomes.

Serum cardiovascular risk biomarkers in pre-pubertal obese children.

BACKGROUND: Childhood obesity is associated with premature cardiovascular complications. However, little is known about the effect of a family-based behavioural intervention on the relationship between arterial function, blood pressure and biomarkers in pre-pubertal children with obesity. DESIGN: This was a single centre randomized controlled trial (RCT) including 74 children randomized to a 6-month behavioural intervention to treat obesity. In 48 children (13 controls and 35 interventions), we assessed: serum level of cytokine (CCL2), adiponectin, and neutrophil product (MMP-8), as well as carotid intima-media thickness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation; arterial stiffness (incremental elastic modulus, Einc), pulse wave velocity (PWV), resting and 24-hour blood pressure (BP). RESULTS: At baseline, resting systolic BP was positively associated with MMP-8 levels which was significantly higher in children with hypertension (P = 0.033). Biochemical markers were not related to endothelial function at baseline, but they globally increased after 6 months in the intervention group. The significant increase of CCL2 levels in the intervention group was associated with a decrease in diastolic BP. Furthermore, adiponectin change was positively related to a change in FMD and negatively to change in Einc and PWV. CONCLUSIONS: The usefulness of serum biomarkers for the detection of cardiovascular diseases is not well established in children. In our population, MMP-8 concentration was higher in hypertensive children. Furthermore, behavioural interventions resulted in a paradoxical increase in some biomarkers in children, with potentially beneficial effects detected with CCL2 changes. Caution should be taken when using nonspecific serum biomarkers for the clinical monitoring of children with obesity.

Airway compression management in late-presenting absent pulmonary valve syndrome.

INTRODUCTION: Patients with absent pulmonary valve syndrome often present early with airway compression from aneurysmal pulmonary arteries. This study reviews our experience in managing absent pulmonary valve syndrome in later presenting children, and techniques used for managing airway compression. METHODS: This study is a retrospective chart review of all patients who underwent repair of absent pulmonary valve syndrome from 2000 to 2012 at our institution. The primary endpoints were post-operative bronchoscopic and clinical evidence of persistent airway compression and need for reinterventions on the pulmonary arteries. RESULTS: A total of 19 patients were included during the study period. The mean age at repair was 4.1±3.0 years (range 10 months-11 years). In all, seven patients had pre-operative bronchoscopic evidence of airway compression, which was managed by pulmonary artery reduction plasty in four patients and Lecompte manoeuvre in three patients. There were no peri-operative deaths. In patients with pulmonary artery plasty, two had no post-operative airway compression, one patient had improved compression, and one patient had unchanged compression. In patients managed with a Lecompte manoeuvre, two patients had no or trivial airway compression and one had improved compression. There were six late reinterventions or reoperations on the pulmonary arteries - two out of four in the pulmonary artery plasty group and one out of three in the Lecompte group. CONCLUSIONS: Most late-presenting patients with absent pulmonary valve syndrome do not have airway compression. Either pulmonary artery reduction plasty or the Lecompte manoeuvre can relieve proximal airway compression, without a significantly different risk of pulmonary artery reintervention between techniques.

Elevated E-selectin and diastolic blood pressure in diabetic children.

BACKGROUND: Cardiovascular risk markers are related to micro-angiopathy in children with type 1 diabetes (T1DM), but there is no information about their relationship with blood pressure (BP) and endothelial function. MATERIALS AND METHODS: This was a case-control study including 29 children with T1DM (mean age 10·5 ± 2·7 years, disease duration: 3·8 ± 2·2 years) and 39 healthy controls (mean age: 9·8 ± 2·7 years). We assessed 24-h ambulatory BP, vascular function and serum level of lipids, vascular cell adhesion molecule-1 (VCAM-1; ICAM) and selectins (E-selectin; P-selectin). RESULTS: The subject groups had similar physical characteristics and lipids level, except body mass index (BMI) which was higher in T1DM than in healthy children (18·6 ± 2·6 vs. 16·7 ± 2·5 kg/m(2), P = 0·003). Children with T1DM had increased 24 h diastolic BP z-score (0·62 ± 0·9 vs. -0·65 ± 0·8, P < 0·001), even after adjustment for BMI, as well as higher VCAM-1 concentration (492 ± 346 vs. 340 ± 225 ng/mL, P = 0·039) compared to healthy subjects. Diastolic BP z-scores were associated with disease duration, E-selectin and triglyceride levels in the T1DM group (P < 0·05). E-selectin was also related to triglycerides, otherwise there were no relationships between vascular function, markers and BP. CONCLUSION: E-selectin, an early atherosclerosis biomarker, is positively associated with diastolic BP values in children with T1DM, despite relatively short disease duration.

Fulminant Infective Endocarditis Due to Kingella Kingae and Several Complications in a 6-Year-Old Girl: A Case Report.

Kingella kingae is a gram-negative coccobacillus belonging to the HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) and is a common oropharyngeal colonizer of healthy young children. Osteoarticular infection is the most commonly reported invasive Kingella kingae infection in children, usually presenting a mild clinical picture. However, it can also cause severe invasive infections, especially infective endocarditis, with a high complication rate. We report the case of a 6-year-old girl, with no past medical history, who presented with fulminant infective endocarditis due to Kingella kingae. She received emergency venoarterial extracorporeal membrane oxygenation support, rapidly underwent cardiac surgery, and was then treated using ceftriaxone for 4 weeks as recommended by the American Heart Association. The patient's postoperative course was marked by a cerebral ischemic stroke consistent with septic embolism. She also presented with a para-aortic pseudoaneurysm that required a secondary surgical procedure, with a good postoperative result. This report illustrates a case of fulminant infective endocarditis due to Kingella kingae and responsible for two major complications. We also describe the preventive valve surgery performed to ensure the preservation of valve function and its capacity for growth.

Preclinical noninvasive markers of atherosclerosis in children and adolescents with type 1 diabetes are influenced by physical activity.

OBJECTIVES: To measure preclinical noninvasive markers of atherosclerosis in youth with type 1 diabetes (T1DM), and to determine their associations between physical activity level and cardiorespiratory fitness (maximal oxygen consumption [VO2max]). STUDY DESIGN: This was a cross-sectional study including 32 patients with T1DM and 42 healthy subjects aged 6 to 17 years. Main outcome measures included arterial flow-mediated dilation (FMD) and intima-media thickness with high-resolution ultrasonography; physical activity by accelerometer (valid 26 patients with T1DM, 35 healthy subjects) and VO2max. RESULTS: Compared with healthy control subjects, patients with T1DM had higher intima-media thickness (mean 0.50 mm [0.48-0.52, 95% CI] vs 0.48 [0.47-0.49], P=.02) and reduced FMD (4.9% [4.1%-5.7%] vs 7.3 [6.4-8.1], P=.001), VO2max (45.5 mL/kg/min [43.0-48.0] vs 48.7 [46.7-50.6], P

A 13-Year-Old Male With Diagnosed Idiopathic Pulmonary Hypertension: Is it Really Idiopathic?

CASE PRESENTATION: A 13-year-old male was referred after incidental finding of cardiomegaly on chest radiograph and signs of pulmonary hypertension on subsequent cardiology consult. He was diagnosed with idiopathic pulmonary hypertension, and came to our center for a second opinion. He was born from consanguineous parents. He reported to be asymptomatic in his daily life. He was not on medications. Family history was not contributive.

Transpulmonary stenting of both pulmonary arteries with a surgical access through redo sternotomy.

We report the case of a four-year-old boy with pulmonary atresia (PA) and ventricular septal defect (VSD) associated with MAPCAs who had a complete repair two times. He developed 21 months later stenosis at the origin of both pulmonary arteries. The conventional interventional catheterization approaches were not available due to femoral vein thrombosis and severe transient complete atrioventricular block due to the manipulations to catheterize the left pulmonary artery. The stenoses were treated by implant of stents using a surgical access to the proximal portion of a Contegra valved conduit (Medtronic, Inc., Minneapolis, MN, USA) by sternotomy.

Rescue circumflex artery stenting for major right ventricular dysfunction after Ross-Konno operation.

A single coronary artery is an anomaly in which only 1 coronary artery arises from the aortic root, supplying the entire heart. We report the case of a 5-year-old girl in whom a single coronary artery ostium was discovered during a Ross-Konno operation. This patient required extracorporeal membrane oxygenation for postoperative right ventricular infarction due to proximal stenosis of a dominant left circumflex artery in combination with an occluded minor right coronary artery. Rescue stent implantation allowed for recovery of right ventricular function and weaning from extracorporeal membrane oxygenation.

Vasoreactive Pulmonary Arterial Hypertension Manifesting With Misleading Epileptic Seizure: Diagnostic and Treatment Pitfalls.

A 5-year-old girl presented with acute nocturnal episodes of loss of consciousness following abdominal pain and crying. Epilepsy was primarily diagnosed but the course of the disease was suggestive of pulmonary hypertension. An adapted invasive assessment of pulmonary pressure and pharmacological challenge allowed for diagnosing vasoreactive pulmonary arterial hypertension. Initial treatment with sildenafil was not effective. Thus, calcium channel blockers were introduced when positive vasoreactivity was confirmed and permitted to stop the occurrence of the syncope and dramatically improved clinical status. At 2 years follow-up she is well without any complaint and in functional class I. Echocardiography shows a slightly enlarged but not hypertrophied right ventricle with a nearly normalized estimated right ventricular pressure. The last catheterization shows subnormal values of pulmonary arterial pressure (mean pulmonary artery pressure: 24 mmHg) and pulmonary vascular resistance (5, 4 Wood units*m2), normalizing with inhaled Nitric Oxide (mean pulmonary artery pressure of 14 mmHg and pulmonary vascular resistance of 1.5 Wood units*m2). Vasoreactive pulmonary arterial hypertension is a rare entity in children but it should not be misdiagnosed with seizures due to the presence of syncopal episodes. According to current knowledge, this form seems to have a better prognosis than non-reactive pulmonary arterial hypertension and the treatment of choice remains as calcium channel blockers. The management of this case was characterized by successive mishaps and potentially harmful mistakes and underscores the potential risk with pediatric PH evaluation in non-expert centers.

Effectiveness of individual and group programmes to treat obesity and reduce cardiovascular disease risk factors in pre-pubertal children.

Childhood obesity results in premature atherosclerosis and requires early intervention. Compare the effectiveness of 6-month lifestyle interventions (with choice of either individual or group therapy) with standard care on body mass index (BMI) z-score and cardiovascular disease (CVD) risks factors in children with obesity. This 6-month randomized controlled trial with a 6-month follow-up included 74 pre-pubertal children with obesity (7.5-11.9 years) assigned randomly (2:1) to intervention or control. Families in the intervention arm choose between an individually delivered treatment (3 hours paediatrician + 4 hours dietician) or group treatment (35 hours with a multidisciplinary team). Children participated also to a weekly physical activity programme. We measured BMI, BMI z-score; waist circumference (WC); total and abdominal fat; blood pressure; common carotid artery intima-media thickness and incremental elastic modulus (Einc); endothelium-dependent and independent dilation (nitroglycerin-mediated dilation [NTGMD]) of the brachial artery; fasting plasma glucose, insulin, lipids; and high-sensitivity C-reactive protein (hs-CRP). Compared to controls, at 6 months, abdominal fat and hs-CRP were reduced in both interventions. The group intervention was also effective in reducing BMI (-0.55 kg/m2 ; 95% confidence interval -1.16 to 0.06) and BMI z-score (-0.08; -0.15 to 0.00) at 6 months and BMI, BMI z-score, WC, NTGMD, total and abdominal fat at 12 months. Abdominal fat and low-grade inflammation were significantly decreased in both interventions. High-intensity group treatment improved early signs of atherosclerosis in children with obesity. These findings are important for the promotion of cardiometabolic health in this population.

Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children.

OBJECTIVE: We investigated whether metabolic syndrome, defined in 3 different ways (2 commonly used and 1 novel) is associated with arterial alterations in obese children. STUDY DESIGN: The study group comprised 384 obese children age 2.5 to 18 years. Blood pressure, fasting blood glucose, blood insulin, plasma lipids, and body composition were measured. Noninvasive ultrasound measurements were obtained in 161 patients to investigate arterial mechanical properties and endothelial function. RESULTS: The prevalence of metabolic syndrome was 10.4%. Intima-media thickness correlated positively with low-density lipoprotein cholesterol (r = .21; P < .01) and negatively with high-density lipoprotein cholesterol (r = -.17; P < .05). In adolescents (11 to 18 years), cross-sectional vascular compliance correlated negatively with abdominal fat (r = -.22; P = .02). The only synergistic effects among individual metabolic syndrome components was an effect of insulinemia and systolic blood pressure on cross-sectional compliance (4.05; P < .05). No significant difference in vascular variables was found between the patients with and without metabolic syndrome using any of the 3 definitions. CONCLUSION: Metabolic syndrome in obese children is not related to arterial variables, whereas several of its individual components are associated with vascular alterations. These data suggest that the value of the metabolic syndrome as a predictor of future cardiovascular events in children remains to be prospectively evaluated. In the meantime, individual cardiovascular risk factors should be evaluated and controlled.

Associations among obesity, blood pressure, and left ventricular mass.

OBJECTIVES: To measure resting and ambulatory systemic blood pressure (BP) and left ventricular mass (LVM) in prepubertal obese and lean children and to determine their relationships. STUDY DESIGN: Cross-sectional study including 44 obese and 22 lean prepubertal children (mean age 8.8 +/- 1.5 years). We measured casual and 24-hour ambulatory BP, LVM and LVM index (LVMI) by echocardiography, and whole body lean tissue and fat mass by dual-energy X-ray absorptiometry. RESULTS: Mean 24-hour systolic BP (124.8 +/- 14.2 vs 105.5 +/- 8.8 mm Hg), diastolic BP (72.8 +/- 7.3 vs 62.7 +/- 3.8 mm Hg), and LVMI (36.1 +/- 5.8 vs 30.9 +/- 5.7, g x m(-2.7)) were significantly higher in obese than in lean subjects. Systolic ambulatory hypertension was present in 47.6% of obese children, and casual BP was normal in 55% of those cases. Body fatness, lean tissue mass, and 24-hour BP correlated positively with LVMI. When adjusted for body fatness, LVMI was only associated with 24-hour systolic BP (adjusted R(2) = 15.9%; P = .001). CONCLUSIONS: Ambulatory systemic hypertension and increased LVM are found in obese children. Left ventricular mass is partially determined by systemic BP. We conclude that prevention and treatment of childhood obesity should be initiated as early as possible to prevent the premature development of hypertension and end-stage organ damage.

Value of brain natriuretic peptide in the perioperative follow-up of children with valvular disease.

OBJECTIVE: To characterize N-terminal pro-brain natriuretic peptide (N-proBNP) and troponin I (TnI) profile following mitral and/or aortic valve surgery and to evaluate correlations with echocardiography measures and outcome criteria. DESIGN AND SETTING: Prospective cross-controlled study in a university children's hospital. PATIENTS: Twenty children with acquired valvular disease requiring valvular surgery. INTERVENTIONS: We prospectively studied clinical, biochemical, and echocardiographic characteristics at baseline and 6, 12, 24 h and 3-4 weeks postoperatively. RESULTS: TnI peaked 6 h after surgery and remained elevated during the first 24 h. N-proBNP was significantly lower 3-4 weeks after surgery than during the perioperative period. Overall, N-proBNP was correlated with the Pediatric Heart Failure Index, left ventricle shortening fraction, left atrium to aorta ratio, left ventricle mass index, end-systolic wall stress, and with outcome measures such as inotropic score, duration of inotropic support, and ICU length of stay. Preoperative N-proBNP was significantly more elevated in patients with complicated outcome than in patients with uneventful postoperative course. CONCLUSIONS: In pediatric valvular patients, perioperative N-proBNP is a promising risk stratification predicting factor. It is correlated with evolutive echocardiographic measures, need for inotropic support, and ICU length of stay.

Two-stage arterial switch for late-presenting transposition of the great arteries.

OBJECTIVES: Ventricular retraining and arterial switch have been described in late-presenting transposition of the great arteries (TGA) in older infants who were unable to undergo neonatal arterial switch operation (ASO) and late survivors of atrial switch with systemic right ventricular dysfunction. There are little data available on patients presenting between these 2 groups. This study aims to review the early and mid-term outcomes of the management of late-presenting TGA with an unprepared left ventricle (LV) by a 2-stage arterial switch. METHODS: The demographic, procedural and outcome data were obtained for all children who underwent LV retraining for late-presenting TGA between 2005 and 2017 at our institution. The primary outcomes were early mortality and extracorporeal membrane oxygenation (ECMO) after arterial switch. RESULTS: Twenty patients were included during the study period, with a median age of 12 months (range 6 weeks-3.3 years). The median time of LV retraining was 48 (range 8-170) days. Indexed LV mass increased from 34 ± 19 g/m2 before LV retraining to 106 ± 85 g/m2 before arterial switch. There was 1 death (5%) after LV retraining. Three patients required ECMO support after arterial switch (15%) despite retraining. During follow-up, there was 1 late death, no late reinterventions or reoperations, and all surviving patients had normal or near-normal LV function at late follow-up. CONCLUSIONS: LV retraining resulted in an increase in LV mass and enabled a 2-stage arterial switch to be carried out with acceptable early and mid-term outcomes. Two-stage arterial switch is a reasonable option for late-presenting TGA. A long-term follow-up is required to assess late LV function after preparation.

Endothelial-dependent vasodilation is impaired in children with sickle cell disease.

Impairment of endothelial-dependent vasodilation has been demonstrated in adults with sickle cell anemia (SCA). We enrolled 21 SCA children, mean age 10.4+/-3.3 yrs, and 23 Afro-Caribbean controls. We examined flow-mediated (FMD) and nitroglycerine-mediated (GTNMD) dilation of the brachial artery, using echotracking techniques, and measured intima-media thickness (IMT) and mechanical properties of the common carotid artery. FMD was significantly decreased in SCA children vs controls (5.6+/-0.2 vs 8.0+/-0.2%, p=0.008), while IMT, stiffness of the common carotid artery, and GTNMD were comparable. In conclusion, endothelial dysfunction is present as early as childhood in SCA patients.

Tissue plasminogen activator for a left atrial thrombus after Senning repair.

OBJECTIVE: To avoid the surgical removal of an obstructive thrombus in a Senning baffle by the administration of recombinant tissue-type plasminogen activator. SETTING: A pediatric intensive care unit in a children's university hospital. PATIENTS: A 3-yr-old male was diagnosed with a large left atrial thrombus 2 wks after Senning repair for D-transposition of the great arteries. The child presented with massive chylous pleural, pericardial effusions, and cardiac tamponade, secondary to partial obstruction of the pulmonary venous channel. INTERVENTION: Thrombolysis with recombinant tissue-type plasminogen activator was instituted. RESULTS: We observed a resolution of the thrombus in <48 hrs. Minor local bleeding was the only noted side effect. No signs of systemic thromboembolization were detected. CONCLUSION: Early thrombolysis with recombinant tissue-type plasminogen activator could be considered a possible alternative to surgical thrombectomy in selected postoperative pediatric cases, although there may be a potential risk of serious bleeding.

Intravenous adenosine for refractory pulmonary hypertension in a low-weight premature newborn: a potential new drug for rescue therapy.

OBJECTIVES: To use intravenous adenosine as a rescue therapy for neonatal refractory pulmonary hypertension in a low-weight premature infant. STUDY LINE: We report the successful use of a continuous intravenous adenosine infusion in a 1150-g premature baby with severe persistent pulmonary hypertension, refractory to classic management with high-frequency oscillatory ventilation, oxygen therapy and inhaled nitric oxide. RESULTS: Adenosine infusion had a dramatic effect allowing for a rapid weaning of oxygen, ventilatory variables, and nitric oxide. CONCLUSIONS: Although experience with continuous adenosine infusion is still at an early stage, it might be worth considering its administration as a rescue therapy or even as an alternative to extracorporeal membrane oxygenation.