Neonatologist-performed point-of-care functional echocardiography in the neonatal intensive care unit.

Functional echocardiography (fECHO) refers to a bedside, limited assessment of the ductus arteriosus, myocardial performance and pulmonary or systemic haemodynamics that is brief in nature and addresses a specific clinical question or management dilemma. This point-of-care ultrasonography is increasingly used internationally and locally among neonatal units to assist with management of neonatal haemodynamic conditions. This article intends to explain the modality, its indications, interpretation and implications for management, and how it impacts long-term outcomes, particularly in chronic lung disease for premature infants born before 32 weeks of gestation. This review will focus on fECHO as a clinical tool to assess the haemodynamics of sick neonates and how it assists in the logical choice for cardiovascular support. Training should be approached as a combined effort between the paediatric cardiology service and neonatology service.

Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes.

AIMS: Long QT syndrome 2 (LQTS2) caused by missense mutations in hERG channel is clinically associated with abnormally prolonged ventricular repolarization and sudden cardiac deaths. Modelling monogenic arrhythmogenic diseases using human-induced pluripotent stem cells (hiPSCs) offers unprecedented mechanistic insights into disease pathogenesis. We utilized LQTS2-hiPSC-derived cardiomyocytes (CMs) to elucidate pathological changes and to demonstrate reversal of LQTS2 phenotype in a therapeutic intervention using a pharmacological agent, (N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine) (ALLN). METHODS AND RESULTS: We generated LQTS2-specific CMs (A561V missense mutation in KCNH2) from iPSCs using the virus-free reprogramming method. These CMs recapitulate dysfunction of hERG potassium channel with diminished IKr currents, prolonged repolarization durations, and elevated arrhythmogenesis due to reduced membrane localization of glycosylated/mature hERG. Dysregulated expression of folding chaperones and processing proteasomes coupled with sequestered hERG in the endoplasmic reticulum confirmed trafficking-induced disease manifestation. Treatment with ALLN, not only increased membrane localization of mature hERG but also reduced repolarization, increased IKr currents and reduced arrhythmogenic events. Diverged from biophysical interference of hERG channel, our results show that modulation of chaperone proteins could be therapeutic in LQTS2 treatment. CONCLUSION: Our in vitro study shows an alternative approach to rescue diseased LQTS2 phenotype via corrective re-trafficking therapy using a small chemical molecule, such as ALLN. This potentially novel approach may have ramifications in other clinically relevant trafficking disorders.

Modeling type 3 long QT syndrome with cardiomyocytes derived from patient-specific induced pluripotent stem cells.

BACKGROUND: Type 3 long QT syndrome (LQT3) is the third most common form of LQT syndrome and is characterized by QT-interval prolongation resulting from a gain-of-function mutation in SCN5A. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of LQT3, which could be used for future drug testing and development of novel treatments for this inherited disorder. METHODS AND RESULTS: Dermal fibroblasts obtained from a patient with LQT3 harboring a SCN5A mutation (c.5287G>A; p.V1763M) were reprogrammed to hiPSCs via repeated transfection of mRNA encoding OCT-4, SOX-2, KLF-4, C-MYC and LIN-28. hiPSC-derived cardiomyocytes (hiPSC-CMs) were obtained via cardiac differentiation. hiPSC-CMs derived from the patient's healthy sister were used as a control. Compared to the control, patient hiPSC-CMs exhibited dominant mutant SCN5A allele gene expression, significantly prolonged action potential duration or APD (paced CMs of control vs. patient: 226.50 ± 17.89 ms vs. 536.59 ± 37.1 ms; mean ± SEM, p < 0.005), an increased tetrodotoxin (TTX)-sensitive late or persistent Na(+) current (control vs. patient: 0.65 ± 0.11 vs. 3.16 ± 0.27 pA/pF; n = 9, p < 0.01), a positive shift of steady state inactivation and a faster recovery from inactivation. Mexiletine, a NaV1.5 blocker, reversed the elevated late Na(+) current and prolonged APD in LQT3 hiPSC-CMs. CONCLUSIONS: We demonstrate that hiPSC-CMs derived from a LQT3 patient recapitulate the biophysical abnormalities that define LQT3. The clinical significance of such an in vitro model is in the development of novel therapeutic strategies and a more personalized approach in testing drugs on patients with LQT3.

Aortic intimal fold in Takayasu arteritis causing obstruction of left coronary ostium.

An 11-year-old girl with Takayasu arteritis was presented with recurrent chest pain. A transthoracic echocardiogram showed moderate to severe aortic regurgitation with impaired cardiac function. Cardiac catheterization revealed the total occlusion of the small right coronary artery and left main stenosis of 40%. An intraoperative transesophageal echocardiogram showed a redundant intimal fold partially covering the left coronary ostium and this was further confirmed from the intraoperative finding. This is a case report of recurrent angina associated with obstruction of left main coronary artery orifice by an intimal fold secondary to Takayasu arteritis.

The effect of Kawasaki disease on childhood allergies - a sibling control study.

OBJECTIVE: Kawasaki disease (KD) is a multisystem inflammatory vasculitis of childhood, with widespread T-helper cell type 1 immune activation. We hypothesize that children who suffered from KD will have a lower risk of developing allergic diseases. STUDY DESIGN: This was a cross-sectional study, recruiting children with a history of KD, together with well sibling controls. All children underwent the standardized core ISAAC questionnaire for allergy, physical examination and skin prick test evaluation. McNemar's test was employed to evaluate the effect of Kawasaki disease on allergy. Multivariable analysis based on mixed-effects logistic regression model was used to adjust for potential confounding effect of age and gender. RESULTS: One hundred and eighty-six children (93 KD sibling pairs) completed the above evaluation. Allergic rhinitis was more common in patients with KD (crude OR 2.40; 95% CI 1.11-5.62, p=0.024) when compared with controls. The effect was further intensified after accounting for the potential confounding effect of age and gender (adjusted OR=2.90; 95% CI 1.27-6.60). Children in whom KD occurred beyond the age of 12 months had more allergic rhinitis (crude OR 4.00, 95% CI 1.29-16.44, p=0.012), 'any' allergies (crude OR 3.75, 95% CI 1.19-15.52, p=0.019) and Blomia tropicalis sensitization (crude OR 2.57, 95% CI 1.02-7.28, p=0.043) when compared with their sibling controls. Interestingly, children in whom KD course resulted in no coronary artery abnormalities have more allergic rhinitis (crude OR 8.50, 95% CI 2.02-75.85, p=0.003) and 'any' allergies (crude OR 5.00, 95% CI 1.41-26.94, p=0.011), when compared with their sibling controls. CONCLUSION: Kawasaki disease may be a risk factor for subsequent allergic diseases. We postulate that KD occurs more frequently in children at risk of immune disequilibrium, with an abnormal inflammatory response initially, and subsequently more allergic manifestations.

Successful drainage of a traumatic haemopericardium with pericardiocentesis through an intercostal approach.

A case of traumatic haemopericardium, sustained after blunt thoracic trauma, is described in a paediatric patient that was successfully drained by needle pericardiocentesis under 2D-echocardiographic guidance, via an intercostal approach, in the Children's Intensive Care Unit. The patient was haemodynamically unstable with obvious signs of cardiac tamponade. Drainage of the haemopericardium resulted in immediate improvement in haemodynamics. There was no re-accumulation of the haemopericardium. There were no complications as a result of the pericardiocentesis. No further surgical intervention was required.

Extracorporeal membrane oxygenation for children with fulminant myocarditis.

The purpose of this study was to evaluate the outcomes of children requiring extracorporeal membrane oxygenation for acute myocarditis. The hospital records of 8 patients who underwent membrane oxygenation for myocarditis from January 2002 to October 2008 were reviewed. Ages ranged from 3 to 12 years (median, 6 years). Duration of membrane oxygenation ranged from 89-502 h. Two patients who collapsed and required cardiac massage prior to membrane oxygenation did not survive. Five (62.5%) patients were discharged well, but one developed dilated cardiomyopathy and died 18 months later. One child had severe mitral regurgitation after weaning from membrane oxygenation, and underwent successful mitral valve repair. Another patient had no cardiac contractility for the initial 2 weeks, but regained good cardiac function after 21 days of support. She was weaned off membrane oxygenation and discharged home well. Complications included left hemiparesis in one patient and left hemothorax in 2. Recovery of cardiac function and a good outcome can be anticipated in children with acute myocarditis requiring membrane oxygenation. Initiation of membrane oxygenation before cardiovascular collapse increases the likelihood of survival.

Late complications following tetralogy of Fallot repair: the need for long-term follow-up.

INTRODUCTION: We report a series of operated tetralogy of Fallot (TOF) patients focusing on complications and outcomes. MATERIALS AND METHODS: Data from TOF patients seen at our centre's adult congenital heart disease clinic was analysed. RESULTS: There were 21 patients: the mean age was 32.2 +/- 12.4 years; the age at first operation was 9.0 +/- 7.9 years; the mean postoperative follow-up duration was 23.5 +/- 12.1 years; and the current New York Heart Association (NYHA) status: I, 82%; II, 4%; III, 14%. Fourteen patients had complete operative notes. All these patients underwent total TOF correction; 2 had staged aortopulmonary shunt with total correction at a mean of 3.2 years later, pulmonary artery patch augmentation in 8 patients and pulmonary valvotomy in 8 patients. Three patients required pulmonary valve homograft replacement for severe pulmonary regurgitation (PR) at 13, 28 and 36 years after the initial corrective operation. CURRENT INVESTIGATIONS: RBBB on ECG (91%), QRS duration 137 +/- 29 ms. Echocardiography showed dilated right ventricular end-diastolic (RVED) diameters (3.2 +/- 0.8 cm); severe PR (67%), residual right ventricular outflow tract obstruction (RVOTO) (42%) and VSD patch leakage (9%). Cardiac magnetic resonance (CMR) (8 patients) showed dilated RVED volumes 252.6 +/- 93.8 mL, indexed RV volume 165.7 +/- 34.8 mL; RV systolic function was preserved in most patients with a RV ejection fraction of 49.5 +/- 5.7%. One patient had atrial tachycardia and another had frequent non-sustained ventricular tachycardia that required radiofrequency ablation. CONCLUSION: Patients with TOF who had full corrective surgery during childhood are now surviving into adulthood. Many challenges arising from complications in the postoperative period remain. It is imperative that adult TOF patients should have regular followup to monitor development and subsequent management of these complications.

Randomized trial of prolonged low-dose versus conventional-dose indomethacin for treating patent ductus arteriosus in very low birth weight infants.

OBJECTIVE: Indomethacin is used for closing the patent ductus arteriosus in premature infants. Prolonged low-dose indomethacin given over 6 days could potentially improve closure rates because ductal constriction is maintained long enough for more effective anatomic closure. We compared the efficacy of this regimen to conventional dosing in a cohort of very low birth weight infants. METHODS: In a 2-arm clinical trial, 140 infants were randomized to either conventional dose (0.2 mg/kg/dose every 12 hours for 3 doses) or prolonged low-dose indomethacin (0.1 mg/kg/dose daily for 6 doses). The primary outcome measure was ductal closure rate, and the secondary outcomes were the need for a second course of treatment, surgical ligation rates, and side effects. RESULTS: Ductal closure after 1 course of indomethacin was similar between the 2 groups: 68% for the conventional dose group and 72% for the prolonged low dose (mean difference -4%; 95% confidence interval: -19% to 11%). The incidence of transient oliguria was higher in the conventional dose group, 31% versus 9%. There was a trend toward more necrotizing enterocolitis in the prolonged low-dose group, 7.0% versus 1.4%. CONCLUSIONS: There was no difference in efficacy between the 2 dosing regimens. In view of this and with its higher incidence of necrotizing enterocolitis, we do not recommend using prolonged low-dose indomethacin for closing the patent ductus arteriosus in very low birth weight infants.

Smith-Magenis syndrome and cyanotic congenital heart disease: a case report.

We report a male newborn infant of Chinese descent with the Smith-Magenis (SMS) syndrome who presented with a severe cyanotic congenital heart disease. This report adds pulmonary atresia and ventricular septal defect to the spectrum of cardiac defects seen in SMS.