Patrizia Salice

Prevalence of the Congenital Long-QT Syndrome

Background— The prevalence of genetic arrhythmogenic diseases is unknown. For the long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published, but none was based on actual data. Our objective was to define the prevalence of LQTS. Methods and Results— In 18 maternity hospitals, an ECG was performed in 44 596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of 28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28 (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%) with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed as affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17 of 43 080 white infants were affected by LQTS, demonstrating a prevalence of at least 1:2534 apparently healthy live births (95% confidence interval, 1:1583 to 1:4350). Conclusions— This study provides the first data-based estimate of the prevalence of LQTS among whites. On the basis of the nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis that this prevalence might be close to 1:2000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.

Focus on prevention, diagnosis and treatment of hypertension in children and adolescents

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem.This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children’s gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child’s age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

Analysis of congenital heart defects in 87 consecutive patients with Brachmann-de Lange syndrome.

Congenital heart defects (CHDs) have been estimated to occur in ∼20% of patients with Brachmann‐de Lange syndrome (BDLS, also known as Cornelia de Lange syndrome, OMIM 122470). We report on the results of a prospective echocardiographic evaluation of a cohort of 87 Italian BDLS patients with longitudinal follow‐up from 5 to 12 years. A cardiac anomaly was identified in 29/87 (33.3%) including 28 (32.2%) patients with a structural CHD, and an additional patient (1.2%) with isolated non‐obstructive hypertrophic cardiomyopathy (HCM). Of the 28 patients with a CHD, 12 (42.9%) had an isolated obstructive CHD, 10 of which were pulmonary stenosis (36%), 8 (28.6%) had an isolated left to right shunt, and the remainder showed a combination of structural anomalies. Overall incidence of pulmonary stenosis was 39% (11/28). Isolated late‐onset mitral or tricuspid valve dysplasia, albeit hemodynamically insignificant, was detected at follow‐up examination in 4 (14.3%) patients older than 10 years, previously known to be normal. In contrast to previous studies, only two patients required surgery, one for closure of a large perimembranous ventricular septal defect (VSD) and associated ASD closure (1), and another for VSD closure and relief of pulmonary valve stenosis (1). The remainder are receiving medical follow‐up. We believe that the overall frequency (33.3%) and evidence of 4 late onset dysplastic valves anomalies justifies both echocardiographic assessment in all BDLS patients at the first diagnostic assessment, and later on during medical follow‐up.

Neonatal lupus: fetal myocarditis progressing to atrioventricular block in triplets

We report a case of neonatal lupus syndrome (NLS) in an in vitro fertilization induced triplet pregnancy. Echocardiographicsigns of myocarditiswere evident at the 21st week of gestation(w.g.) in twin I, with a subsequentdevelopmentof a complete atrioventricular(AV) block at the 25th w.g.; twin III also displayed echocardiographic signs of myocarditis at the same time. Treatment with dexamethasone (4mg/day) was started at the 25th w.g. A complete echocardiographicregression of the myocarditis signs was achieved, while AV block was unaffected.Caesarian section was performed at the 31.5 w.g. after a premature rupture of the membranes. Complete AV block was confirmed in twin I with a heart rate of 51beats/min that required a pacemaker implant 40 days after. Twin III developed a first-degree AV block that switched to a periodic second-degreeblock later, while twin II displayed only liver enzyme abnormalities.

Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection

BackgroundAlthough the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV) infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction.MethodsA total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrolment.ResultsRegardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5%) and 1/35 RSV-negative patients (2.9%) (p < 0.0001). The blocks recurred more than three times over 24 hours in 25/26 RSV-positive patients (96.2%) and none of the RSV-negative infants. Mean and maximum heart rates were significantly higher in the RSV-positive infants (p < 0.05), as was low-frequency power and the low and high-frequency power ratio (p < 0.05). The blocks were significantly more frequent in the children with an RSV load of ≥100,000 copies/mL than in those with a lower viral load (p < 0.0001). Holter ECG after 28 ± 3 days showed the complete regression of the heart abnormalities.ConclusionsRSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm problems and whether they remain asymptomatic and transient even in presence of severe respiratory involvement or chronic underlying disease.

Early Volume Expansion and Outcomes of Hemolytic Uremic Syndrome

BACKGROUND: Hemolytic uremic syndrome associated with Shiga toxin–producing Escherichia coli (STEC-HUS) is a severe acute illness without specific treatment except supportive care; fluid management is concentrated on preventing fluid overload for patients, who are often oligoanuric. Hemoconcentration at onset is associated with more severe disease, but the benefits of volume expansion after hemolytic uremic syndrome (HUS) onset have not been explored. METHODS: All the children with STEC-HUS referred to our center between 2012 and 2014 received intravenous infusion targeted at inducing an early volume expansion (+10% of working weight) to restore circulating volume and reduce ischemic or hypoxic tissue damage. The short- and long-term outcomes of these patients were compared with those of 38 historical patients referred to our center during the years immediately before, when fluid intake was routinely restricted. RESULTS: Patients undergoing fluid infusion soon after diagnosis showed a mean increase in body weight of 12.5% (vs 0%), had significantly better short-term outcomes with a lower rate of central nervous system involvement (7.9% vs 23.7%, P = .06), had less need for renal replacement therapy (26.3% vs 57.9%, P = .01) or intensive care support (2.0 vs. 8.5 days, P = .02), and needed fewer days of hospitalization (9.0 vs 12.0 days, P = .03). Long-term outcomes were also significantly better in terms of renal and extrarenal sequelae (13.2% vs 39.5%, P = .01). CONCLUSIONS: Patients with STEC-HUS had great benefit from early volume expansion. It is speculated that early and generous fluid infusions can reduce thrombus formation and ischemic organ damage, thus having positive effects on both short- and long-term disease outcomes.

Differences between office and ambulatory blood pressures in children and adolescents attending a hospital hypertension clinic.

Background and objectives: Information on ambulatory blood pressure monitoring (ABPM) in children is scarce. While in adults office BP (OBP) is higher than ABP and the difference increases as OBP increases, information in children suggests that at this young age ABP is no lower and often higher than OBP. This study was aimed at describing OBP–ABP differences in a cohort of children of different ages and BPs, and investigating whether OBP–ABP differences are dependent on age or OBP level. Methods: We retrospectively compared OBP and 24-h, daytime and night-time ABP in 433 children and adolescents aged 4–18 years, referred to our hospital clinic. Results: OBP was found to be significantly lower than 24-h and daytime ABP in the low age tertile (4–10 years) but not in the medium and high tertiles. OBP was also lower than ABP in normotensive patients (n = 182), but higher than ABP in untreated hypertensive patients (n = 92) despite similar ages. Continuous analyses showed a weak correlation of OBP–ABP differences with age, and a much stronger correlation with OBP so that 24-h ABP was higher than OBP at OBP values less than 117/73 mmHg and lower than OBP at higher OBP values. Logistic regression analysis indicates that also in children OBP accounts for most of the OBP–ABP difference. Conclusion: There is a common relation both in children and adults between OBP and ABP. It is only because high OBP is common in the elderly, and the lowest OBP is usually found in young children that large positive OBP–ABP differences have been associated with old age, and negative differences with childhood. OBP–ABP differences, often defined as white-coat effect, can have different directions and are likely to be largely due to regression to the mean.

Double aortic arch in neonates: optimal definition by means of contrast-enhanced helical CT scan

A female neonate born, after a regular pregnancy, at 38+6 weeks of gestation and weighing 3065 g developed a severe respiratory distress after few hours of life, requiring intubation and mechanical ventilation. Despite ventilatory assistance and a chest x-ray not suggestive of pulmonary disease, she had persistent dyspnoea. An attempt to adjust the endotracheal tube position with juxta-carinal placement was correlated with an …

Flecainide as first-line treatment for supraventricular tachycardia in newborns.

Background Flecainide for the treatment of supraventricular tachycardia (SVT) in newborns is still controversial because of its potentially severe proarrhythmic effects. Methods and results Between January 2004 and December 2006, we used flecainide to treat 20 consecutive newborns (15 males) with paroxysmal SVT without any structural heart disease. Their age at hospitalization was 11.5 ± 11.1 days. The intravenous administration of flecainide (1 mg/kg) effectively restored sinus rhythm in all the patients. Once stable sinus rhythm had been restored, the drug was administered orally at a dose of 2 mg/kg/day twice daily, which was uptitrated as the patients gained weight. The patients were followed up for up to 24 months with clinical evaluations, baseline ECG and 24-h Holter monitoring every 3 months. There were neither deaths nor any episodes of heart failure or sustained ventricular tachycardia during follow-up. SVT were completely controlled in 17 patients (85%), with an oral dose of 3.35 ± 1.35 mg/kg/day of flecainide; in the remaining three patients with refractory arrhythmias, propranolol was added for optimal treatment. No significant increase in the duration of QRS (70 ± 1.09 vs. 63.8 ± 1.87 ms, P = NS) or any significant QTc prolongation (413 ± 7.4 vs. 412.6 ± 8.01 ms, P = NS) was observed. One patient developed an incomplete right bundle branch block promptly reverted by reducing the dose. Conclusion This preliminary experience indicates that flecainide is well tolerated and effective as first-line treatment for paroxysmal SVT in newborns without structural heart disease.

Effect of highly active antiretroviral therapy on cardiovascular involvement in children with human immunodeficiency virus infection

The impact of highly active antiretroviral therapy (HAART) on cardiovascular involvement was evaluated in 38 vertically human immunodeficiency virus-infected children followed up for 5 years. This study demonstrates for the first time in a cohort of children the resolution of previous dilated cardiomyopathy after the start of HAART and the absence of cardiovascular events related to metabolic abnormalities during the period of its administration.