Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension.

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. METHODS: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. RESULTS: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. CONCLUSION: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Readiness for Hospital Discharge, Stress, and Coping in Mothers of Children Undergoing Cardiac Surgeries: A Single-Center Prospective Study.

OBJECTIVES: To examine the relationship between stress, coping, and discharge readiness in mothers of children undergoing congenital heart surgeries. DESIGN: Quantitative descriptive study at three time points: pre surgery (time point I), day of hospital discharge (time point II) and 2 weeks following discharge (time point III). SETTING: Tertiary care pediatric hospital in Singapore. PARTICIPANTS: One hundred mothers whose children had undergone congenital heart surgeries. MEASUREMENTS AND MAIN RESULTS: Data collection included self-reported questionnaires of the Pediatric Inventory for Parents and the Coping Health Inventory for Parents across three time points. Readiness for Hospital Discharge Scale was administered at hospital discharge (time point II). The utilization of health services and support was reported at post discharge (time point III). One-hundred mothers participated in this study between May 2016 and July 2017. Their mean age was 35.8 years (SD = 7.0), and the mean age of their children was 3.7 years (SD = 4.6). There was significant reduction in mean stress difficulty (Pediatric Inventory for Parents) of mothers (F = 4.58; p = 0.013) from time point I to III. No significant changes were found in the overall mean coping score (Coping Health Inventory for Parents) of mothers across time. The mean overall score for the readiness for discharge (Readiness for Hospital Discharge Scale) of mothers at hospital discharge was 207.34 (SD = 29.22). Coping through family integration subscale and communication stress predicted discharge readiness of mothers (adjusted R = 0.11; p = 0.034). Mothers who reported higher overall stress (Pediatric Inventory for Parents) 2 weeks post discharge were more likely to call a friend or family member, visit the emergency department, or have their child readmitted to hospital following hospital discharge. CONCLUSIONS: We identified coping by family integration and communication-related stress as predictors of readiness for discharge. Strategies targeted at communication and family integration for discharge preparation may improve caregivers' readiness for hospital discharge.

Loeys-Dietz syndrome in a Southeast Asian Hospital: a case series.

UNLABELLED: Loeys-Dietz syndrome (LDS) is a heritable connective tissue disease in which the activity of the transforming growth factor (TGF) beta signalling pathway is disrupted. The clinical features of LDS represent a clinical continuum that includes LDS type 1, with cutaneous, vascular, skeletal and craniofacial findings, and LDS type 2, with cutaneous, vascular and skeletal findings. We describe five Asian patients with genetically confirmed LDS with mutations in either the TGFBR1 or TGFBR2 gene. Their clinical features were similar to those reported in Caucasian patients. Two patients have novel mutations in TGFBR2. Transcatheter occlusion of patent ductus arteriosus (PDA) was safe and successful in three patients. Treatment with Losartan for aortic root dilatation was well tolerated in our patients, but the outcome is mixed. Among the three patients with follow-up data, aortic root dilatation has improved in two patients but continues to progress in the third patient despite treatment. CONCLUSION: We describe two novel mutations in TGFBR2 leading to LDS; PDA is common in our patients and can be safely occluded via transcatheter procedure.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

Objectives: To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Design: Prospective observational study. Setting: Single-center, tertiary-level neonatal intensive care unit. Patients: Infant born <28 weeks gestation. Main outcome measures: Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. Results: A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. Conclusions: TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Types and distribution of congenital heart defects associated with trisomy 21 in Singapore.

AIM: Atrioventricular septal defect (AVSD) is widely accepted as the most common type of congenital heart defect in trisomy 21. Most of these studies, however, were conducted in Caucasian communities. The few Asian studies that had been conducted on this subject yielded different results. In the largest study of its kind in Asia, we described the distribution of types of congenital heart defects associated with trisomy 21 in Singapore. METHODS: Five hundred and eighty-eight patients with trisomy 21 born in 1996-2010, and confirmed by karyotyping, were included in the study. The diagnosis of congenital heart defects were made on echocardiography. Variables extracted for analysis were demographics (race and gender) and the types of congenital heart defects. Except for complex cyanotic heart defects, haemodynamically significant lesions were accounted for separately in cases where more than one type of congenital heart defect coexisted in a patient. RESULTS: Ventricular septal defect (VSD) (39.2%) was the most common congenital heart defect associated with trisomy 21 in our study, followed by patent ductus arteriosus (34.3%), secundum atrial septal defect (23.4%) and AVSD (15.6%). This study validates previous smaller Asian studies identifying VSD as the most common cardiac lesion associated with trisomy 21. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs. Coarctation of the aorta was uncommon. CONCLUSION: VSD was the most common congenital heart defect seen in trisomy 21 in our study. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs.

Endocardial Fibroelastosis as an Independent Predictor of Atrioventricular Valve Rupture in Maternal Autoimmune Antibody Exposed Fetus: A Systematic Review with Clinicopathologic Analysis.

BACKGROUND: Neonatal lupus (NL) is a clinical syndrome that develops in the fetus as a result of maternal autoimmune antibodies. Congenital complete heart block (CHB) is the most common manifestation, while extranodal cardiac manifestations of NL, such as endocardial fibroelastosis (EFE) and myocarditis, are rare but more serious. Less is known about this atrioventricular valve rupture due to valvulitis as a consequence of maternal autoantibodies. We have described a case of cardiac neonatal lupus with an antenatally detected CHB patient who developed mitral and tricuspid valve chordal rupture at 45 days of age. We compared the cardiac histopathology and the fetal cardiac echocardiographic findings of this case with another fetus that was aborted after being antenatally diagnosed with CHB but without valvar rupture. A narrative analysis after a systematic review of the literature regarding atrioventricular valve apparatus rupture due to autoimmune etiology along with maternal characteristics, presentation, treatment, and outcome have been discussed in this article. OBJECTIVES: To describe published data on atrioventricular valve rupture in neonatal lupus, including clinical presentation, diagnostic evaluation, management, and outcomes. METHODS: We conducted a PRISMA-compliant descriptive systematic examination of case reports that included accounts of lupus during pregnancy or in the newborn period that resulted in an atrioventricular valve rupture. We gathered information on the patient's demographics, the details of the valve rupture and other comorbidities, the maternal therapy, the clinical course, and the results. We also used a standardized method to evaluate the cases' quality. A total of 12 cases were investigated, with 11 cases drawn from 10 case reports or case series and 1 from our own experience. RESULTS: Tricuspid valve rupture (50%) is more common than mitral valve rupture (17%). Unlike mitral valve rupture, which occurs postnatally, the timing of tricuspid valve rupture is perinatal. A total of 33% of the patients had concomitant complete heart block, while 75% of the patients had endocardial fibroelastosis on an antenatal ultrasound. Antenatal changes pertaining to endocardial fibroelastosis can be seen as early as 19 weeks of gestation. Patients with both valve ruptures generally have a poor prognosis, especially if they occur at close intervals. CONCLUSION: Atrioventricular valve rupture in neonatal lupus is rare. A majority of patients with valve rupture had antenatally detected endocardial fibroelastosis in the valvar apparatus. Appropriate and expedited surgical repair of ruptured atrioventricular valves is feasible and has a low mortality risk. Rupture of both atrioventricular valves occurring at close intervals carries a high mortality risk.

Medical Management of Infants With Supraventricular Tachycardia: Results From a Registry and Review of the Literature.

Background: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT. Methods: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. Results: A total of 2534 infants were included: n = 108 from the registry (median age, 9 days [0-324 days], 70.8% male) and n = 2426 from the literature review (median age, 14 days; 62.3% male). Propranolol was the most prevalent acute (61.4%) and maintenance treatment (53.8%) in the Registry, whereas digoxin was used sparingly (4.0% and 3.8%, respectively). Propranolol and digoxin were used frequently in the literature acutely (31% and 33.2%) and for maintenance (17.8% and 10.1%) (P < 0.001). No differences in acute or prophylactic effectiveness between medications were observed. Recurrence was higher in the Registry (25.0%) vs literature (13.4%) (P < 0.001), and 22 (0.9%) deaths were reported in the literature vs none in the Registry. Conclusion: This was the largest cohort of infants with SVT analysed to date. Digoxin monotherapy use was rare amongst contemporary paediatric cardiologists. There was limited evidence to support one medication over another. Overall, recurrence and mortality rates on antiarrhythmic treatment were low.

Contexte: De nombreux choix de médicaments existent pour le traitement aigu et prophylactique de la tachycardie supraventriculaire (TSV) réfractaire chez les nourrissons. Or, il n'y a presque pas d'essais contrôlés à ce sujet, et les choix de médicaments ne sont pas nécessairement fondés sur des données probantes. Notre objectif était de faire état de l'efficacité des stratégies de prise en charge de la TSV chez les nourrissons. Méthodologie: Un registre des nourrissons admis à l'hôpital pour une TSV par réentrée, sans cardiopathie d'importance hémodynamique, a été tenu de façon prospective dans 11 centres de soins tertiaires à l'échelle mondiale. De plus, une revue systématique des études sur la TSV par réentrée chez le nourrisson a été effectuée dans MEDLINE et EMBASE. Des données sur les caractéristiques démographiques, les symptômes, les traitements aigus et d'entretien, et les résultats ont été recueillis. Résultats: Un total de 2 534 nourrissons ont été inclus : n = 108 du registre (âge médian de 9 jours [0-324 jours], 70,8 % de sexe masculin) et n = 2 426 de la revue de la littérature (âge médian de 14 jours; 62,3 % de sexe masculin). Le propranolol était le traitement de soins aigus (61,4 %) et d'entretien (53,8 %) le plus fréquent dans le registre, alors que la digoxine a été utilisée occasionnellement (respectivement dans 4,0 % et 3,8 % des cas). Dans la littérature, le propranolol et la digoxine étaient fréquemment utilisés en soins aigus (31 % et 33,2 %) et en traitement d'entretien (17,8 % et 10,1 %) (p < 0,001). Aucune différence n'a été observée entre les médicaments au chapitre de l'efficacité du traitement de soins aigus ou du traitement prophylactique. Le taux de récurrence était plus élevé dans le registre (25,0 %) que dans la littérature (13,4 %) (p < 0,001), et 22 (0,9 %) décès ont été signalés dans la littérature, mais aucun dans le registre. Conclusion: Il s'agit de la plus grande cohorte de nourrissons atteints de TSV analysée à ce jour. De nos jours, les cardiologues pédiatriques prescrivent rarement la digoxine en monothérapie. Peu de données probantes favorisent l'utilisation d'un médicament par rapport à l'autre. Dans l'ensemble, les taux de récurrence et de mortalité sous traitement antiarythmique étaient faibles.

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.

Screening for congenital heart disease in a Singapore neonatal unit.

INTRODUCTION: Congenital heart disease (CHD) is a leading cause of infant mortality. The aim of this study was to evaluate the efficacy of a neonatal screening programme for CHD before the introduction of pulse oximetry. METHODS: This was a retrospective review of live births in the period 2003-2012. Cases of CHD were detected through prenatal ultrasonography and/or postnatal examination, and confirmed using two-dimensional echocardiography. Data was rigorously checked against multiple sources. The antenatal detection rate, sensitivity, specificity, predictive values and likelihood ratios of the screening programme were analysed for all cases of CHD and critical CHD. RESULTS: The incidence of CHD was 9.7 per 1,000 live births. The commonest CHD was ventricular septal defect (54.8%). The antenatal detection rate was three times higher in the critical CHD group (64.0%) compared to the group as a whole (21.1%). The sensitivity and specificity of screening was 64.5% and 99.7% for all CHD, and 92.9% and 99.1% for the critical CHD group, respectively. The positive likelihood ratio was 215 and 103, while the negative likelihood ratio was 0.36 and 0.07 for all CHD and critical CHD, respectively. CONCLUSION: The CHD screening programme had excellent specificity but limited sensitivity. The high positive likelihood ratios indicate that where sufficient risk factors for CHD are present, a positive result effectively confirms the presence of CHD. The low negative likelihood ratio for critical CHD indicates that, where prior suspicion for critical CHD is low, a negative result is reassuring.

Age- and Sex-Specific Changes in CMR Feature Tracking-Based Right Atrial and Ventricular Functional Parameters in Healthy Asians.

Cardiovascular magnetic resonance (CMR) is the reference standard for non-invasive assessment of right-sided heart function. Recent advances in CMR post-processing facilitate quantification of tricuspid annular (TA) dynamics and longitudinal strains of the right ventricle (RV) and right atrium (RA). We aimed to determine age- and sex-specific changes in CMR-derived TA dynamics, and RV and RA functional parameters in healthy Asian adults. We studied 360 healthy subjects aged 21-79 years, with 30 men and 30 women in each of the six age groups. Functional parameters of RV and RA were measured on standard four-chamber cine CMR using fast feature tracking: (1) TA peak velocities (systolic velocity S', early diastolic velocity E', late diastolic velocity A') and TA plane systolic excursion (TAPSE); (2) RV global longitudinal strain (GLS) and strain rates; and (3) RA phasic longitudinal strains and strain rates. S' and TAPSE exhibited negative correlations with age. RV GLS was significantly higher in females than in males but not associated with age in both sexes. Females had similar E', lower A', and higher E'/A' ratios compared to males. Positive associations of E' and E'/A', and negative association of A' with age were observed in both sexes. Females had higher RA reservoir and conduit strains compared to males. There were significantly negative and positive associations between RA conduit and booster strains, respectively, with age. Age- and sex-specific reference ranges were established, and associations revealed, for fast CMR feature tracking parameters of right heart function in a large normal Asian population.

Successful pharmacological management of a child with compound heterozygous familial hypercholesterolemia and review of the recent literature.

Severe familial hypercholesterolemia (SFH) is characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) and severe early-onset cardiovascular disease if left untreated. We report on the decade-long therapeutic journey of a 15-year-old boy with SFH due to a severe compound heterozygous genotype. He presented at the age of 5 years with widespread xanthomas and LDL-C of 17.4 mmol/L. He was diagnosed with SFH, initially treated with colestyramine that was subsequently combined with simvastatin. At the age of 12 years, he was diagnosed to have supravalvular aortic stenosis and ezetimibe/atorvastatin was introduced in place of colestyramine/simvastatin. At the age of 14 years, he received triple therapy with evolocumab, initially at the recommended dose of 420 mg monthly and then reduced to 140 mg biweekly. Currently at the age of 15 years, he is on atorvastatin 40 mg ON, ezetimibe 10 mg OM, and evolocumab 140 mg biweekly, achieving LDL-C levels of 2.4 mmol/L. Genetic testing identified compound heterozygous mutations in the LDL receptor genes [c.(940 + 1_941-1) (1845 + 1_1846-1)dup] and exon 12, nucleotide c.1747 C > T, amino acid p.(His583Tyr). Medical management without lipoprotein apheresis can achieve target LDL-C in children with SFH. Our patient, who developed supravalvular aortic stenosis at the age of 12 years, needed early aggressive treatment when SFH guidelines and newer drugs for young children were unavailable. Our patient demonstrated that 140 mg biweekly of evolocumab has the same cholesterol-lowering effect as the recommended 420 mg monthly dose.

Reperfusion Injury with Compartment Syndrome Following Systemic Thrombolysis for Cardiac Catheterization-Related Arterial Thrombosis in an Infant.

Systemic thrombolysis is increasingly used for management of arterial thrombosis following cardiac catheterization, and complications apart from bleeding manifestations are not well reported. We report the case of an infant with lower limb ischemia secondary to femoral arterial thrombosis, which developed after cardiac catheterization. Systemic thrombolysis resulted in successful reperfusion of the lower limb. However, the infant subsequently developed compartment syndrome, requiring an emergent fasciotomy. This case highlights the importance of surveillance for the development of reperfusion injury-related compartment syndrome postsystemic thrombolysis for arterial thrombosis.

The Impact of Pre-operative Nutritional Status on Outcomes Following Congenital Heart Surgery.

Aims and Objectives: Malnutrition is common in children with congenital heart disease and may contribute to adverse outcomes. This study evaluates the impact of pre-operative nutritional status on outcomes after congenital heart surgery. Methods: We conducted a retrospective cohort study enrolling children under 10 years old who underwent congenital heart surgery at a tertiary children's hospital from 2012 to 2016. Patients who had patent ductus arteriosus ligation only, genetic syndromes, or global developmental delay were excluded. Outcome measures included 30-day mortality, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of mechanical ventilation, and number of inotropes used post-operatively. We performed univariate/multivariable logistic regression analysis, adjusting for age, cyanotic cardiac lesion, co-morbidity, and Risk Adjustment for Congenital Heart Surgery (RACHS-1) score. Results: Three hundred two children of median age 16.2 [interquartile range (IQR) 3.1, 51.4)] months were included. The most common cardiac lesions were ventricular septal defect (27.8%), atrial septal defect (17.9%), and Tetralogy of Fallot (16.6%). Median weight-for-age z-score (WAZ) was -1.46 (IQR -2.29, -0.61), height-for-age z-score (HAZ) was -0.94 (IQR -2.10, -0.10), and body mass index (BMI)-for-age z-score (BAZ) was -1.11 (IQR -2.19, -0.30). In multivariable analysis, there was an increased risk of 30-day mortality for WAZ ≤-2 vs. WAZ >-2 [adjusted odds ratio (aOR): 4.01, 95% CI: 1.22, 13.13; p = 0.022]. For HAZ ≤-2 vs. HAZ > -2, there was increased risk of hospital LOS ≥ 7 days (aOR: 2.08, 95% CI: 1.12, 3.89; p = 0.021), mechanical ventilation ≥48 h (aOR: 2.63, 95% CI: 1.32, 5.24; p = 0.006) and of requiring ≥3 inotropes post-operatively (aOR: 3.00, 95% CI: 1.37, 6.59; p = 0.006). Conclusion: In children undergoing congenital heart surgery, WAZ ≤ -2 is associated with higher 30-day mortality, while HAZ ≤ -2 is associated with longer durations of hospital LOS and mechanical ventilation, and increased risk of use of 3 or more inotropes post-operatively. Future studies are necessary to develop safe and efficacious peri-operative nutritional interventions, particularly in patients with WAZ and HAZ ≤ -2.

Nutritional practices and adequacy in children supported on extracorporeal membrane oxygenation.

BACKGROUND AND AIMS: Use of extracorporeal membrane oxygenation (ECMO) in children is increasing. Yet, little is known about optimal nutritional practices in these children. We aim to describe the nutritional adequacy, factors associated with enteral nutrition, and the association between nutritional adequacy and mortality in children supported on ECMO. METHODS: We conducted a retrospective review of all children (1 month-18 years) requiring ECMO between 2010 and 2016. Data on enteral and parenteral energy and protein intake in the first 7 days of ECMO were collected. Adequacy of nutrition intake was defined as total intake vs. total requirements, expressed as a percentage. RESULTS: 51 patients were included, of which 43 (84.3%) were supported on veno-arterial ECMO. Median ECMO duration was 8.6 days [interquartile range (IQR) 6.1-16.2]. Overall energy and protein adequacy across the first 7 days of ECMO were 48.3% (IQR 28.0-67.4) and 44.8% (IQR 26.9-67.0) respectively. Parenteral nutrition provided majority of calories [median 88.0% (IQR 62.9-100)] and protein [median 91.0% (IQR 62.3-100)] intake. Enteral nutrition (EN) was initiated in 33 (64.7%) patients. Time to EN initiation, vasoactive-inotropic score just before ECMO initiation, veno-arterial ECMO mode and continuous renal replacement therapy in the first week of ECMO were factors associated with EN energy adequacy. Hospital mortality rate was 55% (28/51). Compared to survivors, non-survivors had lower adequacy of EN energy intake [0.5% (IQR 0-4.4) vs. 11.8% (IQR 0-24.5), p = 0.034]. After correcting for ECMO duration, need for continuous renal replacement therapy and number of vasoactive drugs required on ECMO, greater EN energy adequacy remained associated with lower risk of mortality [adjusted odds ratio 0.93 (95% confidence interval: 0.86-0.99), p = 0.048]. CONCLUSIONS: Nutritional adequacy, especially that of EN, remains low in children supported on ECMO. EN energy adequacy was found to be associated with lower mortality. Further studies on nutritional adequacy in pediatric ECMO, as well as strategies to optimize EN in these children, are warranted.

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.

The Impact of Time to Rate Control of Junctional Ectopic Tachycardia After Congenital Heart Surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) after congenital heart disease (CHD) surgery is often self-limiting but is associated with increased risk of morbidity and mortality. Contributing factors and impact of time to achieve rate control of JET are poorly described. METHODS: From January 2010 to June 2015, a retrospective, single-center cohort study was performed of children who developed JET after CHD surgery . We classified the cohort into two groups: patients who achieved rate control of JET in ≤24 hours and in >24 hours. We examined factors associated with time to rate control and compared clinical outcomes (mortality, duration of mechanical ventilation, length of intensive care unit [ICU], and hospital stay) between the two groups. RESULTS: Our cohort included 27 children, with a median age of 3 (interquartile range: 0.7-38] months. The most common CHD lesions were ventricular septal defect (n = 10, 37%), tetralogy of Fallot (n = 7, 25.9%), and transposition of the great arteries (n = 4, 14.8%). In all, 15 (55.6%) and 12 (44.4%) patients achieved rate control of JET in ≤24 hours and >24 hours, respectively. There was a difference in median mechanical ventilation time (97 [21-145) vs 311 [100-676] hours; P = .013) and ICU stay (5.0 [2.0-8.0] vs 15.5 [5.5-32.8] days, P = .023) between the patients who achieved faster rate control than those who didn't. There was no difference in length of hospital stay and mortality between the groups. CONCLUSION: Our study demonstrated that time to achieve rate control of JET was associated with increased duration of mechanical ventilation and ICU stay.

Neonatal and Paediatric Extracorporeal Membrane Oxygenation (ECMO) in a Single Asian Tertiary Centre.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass technique (CPB) which provides life-saving support in patients with refractory cardiorespiratory failure until cardiopulmonary recovery or organ replacement. MATERIALS AND METHODS: This is a single centre retrospective study reporting the largest series of paediatric patients in Singapore who received ECMO support over an 11-year period from January 2002 to December 2012. The objective is to describe the characteristics of the patients and to report the survival to hospital discharge, complications during ECMO and other long-term complications. RESULTS: Forty-eight patients received ECMO during the study period. ECMO was initiated for myocarditis in majority of the paediatric patients whereas postoperative low cardiac output state was the most common indication in the neonatal population. The overall survival rate to hospital discharge was 45.8%. Survival was highest in the neonates with respiratory failure (75%). Haematological and cardiac complications were most common during ECMO. Age group, gender, duration of ECMO, need for renal replacement therapy, acute neurological complications were not associated with mortality. Those needing inotropic support during ECMO had poorer survival while those with hypertension requiring vasodilator treatment had a higher survival rate. The survival rates for ECMO patients more than doubled from the initial 6 years of 23% to 54% in the last 5 years of the study period. Long-term complications encountered included neurological, respiratory and cardiac problems. CONCLUSION: ECMO is a life-saving modality for neonatal and paediatric patients with cardiopulmonary failure from diverse causes. Patients with persistent need for inotropes during ECMO had poorer outcome. Centre experience had an impact on ECMO outcome.