Objective: Symptomatic neonates with Ebstein’s anomaly pose significant challenge. Within this cohort, neonates with associated anatomical pulmonary atresia have higher mortality. We review our experience with this difficult subset. Methods: A total of 32 consecutive symptomatic neonates with Ebstein’s anomaly underwent surgical intervention between 1994 and 2013. Of them, 20 neonates (62%, 20/32) had associated pulmonary atresia. Patients’ weights ranged from 1.9 to 3.4 kg. All patients without pulmonary atresia had two-ventricle repair. Of the 20 neonates, 16 (80%, 16/20) with Ebstein’s anomaly and pulmonary atresia had two-ventricle repair and 4 had single-ventricle palliation, of which 2 underwent Starnes’ palliation and 2 Blalock–Taussig shunts. Six recent patients with Ebstein’s anomaly and pulmonary atresia had right ventricle to pulmonary artery valved conduit as part of their two-ventricle repair. Results: Overall early mortality was 28% (9/32). For those without pulmonary atresia, mortality was 8.3% (1/12). For the entire cohort of neonates with Ebstein’s anomaly and pulmonary atresia, mortality was 40% (8/20; p=0.05). Mortality for neonates with Ebstein’s anomaly and pulmonary atresia having two-ventricle repair was 44% (7/16). Mortality for neonates with Ebstein’s anomaly and pulmonary atresia having two-ventricle repair utilising right ventricle to pulmonary artery conduit was 16% (1/6). For those having one-ventricle repair, the mortality was 25% (1/4). Conclusions: Surgical management of neonates with Ebstein’s anomaly remains challenging. For neonates with Ebstein’s anomaly and anatomical pulmonary atresia, single-ventricle palliation is associated with lower early mortality compared with two-ventricle repair. This outcome advantage is negated by inclusion of right ventricle to pulmonary artery conduit as part of the two-ventricle repair.

Aim: The use of β-blocker therapy in asymptomatic patients with hypertrophic cardiomyopathy is controversial. This study evaluates the effect of lifestyle changes and high-dose β-blocker therapy on their exercise capacity. Methods and results: A total of 29 consecutive newly diagnosed asymptomatic patients with familial hypertrophic cardiomyopathy, median age 15 years (range 7–25), were recruited. In all, 16 patients with risk factors for sudden death were treated with propranolol if no contraindications, or equivalent doses of metoprolol; 13 with no risk factors were randomised to metoprolol or no active treatment. Thus, there were three treatment groups, non-selective β-blockade (n=10, propranolol 4.0–11.6 mg/kg/day), selective β-blockade (n=9, metoprolol 2.7–5.9 mg/kg/day), and randomised controls (n=10). All were given recommendations for lifestyle modifications, and reduced energetic exercise significantly (p=0.002). Before study entry, and after 1 year, all underwent bicycle exercise tests with a ramp protocol. There were no differences in exercise capacity between the groups at entry, or follow-up, when median exercise capacity in the groups were virtually identical (2.4, 2.3, and 2.3 watt/kg and 55, 55, and 55 watt/(height in metre)2 in control, selective, and non-selective groups, respectively. Maximum heart rate decreased in the selective (−29%, p=0.04) and non-selective (−24%, p=0.002) groups. No patient developed a pathological blood-pressure response to exercise because of β-blocker therapy. Boys were more frequently risk-factor positive than girls (75% versus 33%, p=0.048) and had higher physical activity scores than girls at study-entry (p=0.011). Conclusions: Neither selective nor non-selective β-blockade causes significant reductions in exercise capacity in patients with hypertrophic cardiomyopathy above that induced by lifestyle changes.

Background: We have previously identified risk factors for readmission following congenital heart surgery – Hispanic ethnicity, failure to thrive, and original hospital stay more than 10 days. As part of a quality initiative, changes were made to the discharge process in hopes of reducing the impact. All discharges were carried out with an interpreter, medications were delivered to the hospital before discharge, and phone calls were made to families within 72 hours following discharge. We hypothesised that these changes would decrease readmissions. Methods: The current cohort of 635 patients underwent surgery in 2012. Demographic, preoperative, operative, and postoperative variables were evaluated. Univariate and multivariate risk factor analyses were performed. Comparisons were made between the initial (2009) and the current (2012) cohorts. Results: There were 86 readmissions of 77 patients during 2012. Multivariate risk factors for readmission were risk adjustment for congenital heart surgery score and initial hospital stay >10 days. In comparing 2009 with 2012, the overall readmission rate was similar (10 versus 12%, p=0.27). Although there were slight decreases in the 2012 readmissions for those patients with Hispanic ethnicity (18 versus 16%, p=0.79), failure to thrive (23 versus 17%, p=0.49), and initial hospital stay >10 days (22 versus 20%, p=0.63), they were not statistically significant. Conclusions: Potential risk factors for readmission following paediatric cardiothoracic surgery have been identified. Although targeted modifications in discharge processes can be made, they may not reduce readmissions. Efforts should continue to identify modifiable factors that can reduce the negative impact of hospital readmissions.

It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an important role in the development of cardiomyopathy, and various types of cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies have described many mutations in mitochondrial genes encoding for subunits of respiratory chain complexes. Thus, recent studies confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a major reason of diseases and determining them by next-generation sequencing will improve our understanding of dysregulation of heart development. To analyse mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction fragments from the cardiac tissue of the 22 patients with congenital heart disease, undergoing cardiac surgery. Mitochondrial deoxyribo nucleic acid was deep sequenced by next-generation sequencing. A total of 13 novel mitochondrial deoxyribo nucleic acid mutations were identified in nine patients. Of the patients, three have novel mutations together with reported cardiomyopathy mutations. In all, 65 mutations were found, and 13 of them were unreported. This study represents the most comprehensive mitochondrial deoxyribo nucleic acid mutational analysis in patients with congenital heart disease.

Extrapolating cardiac resynchronization therapy (CRT) to pediatric patients with heart failure has at times been difficult given the heterogeneity of pediatric cardiomyopathies, varying congenital heart disease (CHD) substrates, and the fact that most pediatric heart failure patients have right bundle branch block (RBBB) as opposed to LBBB. Yet, despite these limitations a number of multi-center retrospective studies in North America and Europe have identified some data to suggest that certain sub-populations tend to respond positively to CRT. In order to address some of the heterogeneity it is helpful to subdivide pediatric and young adult patients with CHD into four potential groups: (1) CRT for chronic RV pacing, (2) dilated cardiomyopathies, (3) pulmonary right ventricles, and (4) systemic right ventricles. The chronic RV paced group, especially long-standing RV apical pacing, with ventricular dyssynchrony has consistently shown to be the group that best responds to a proactive resynchronization course. CRT therapy in pulmonary right ventricles such as post-op tetralogy of Fallot have shown some promise and may be considered especially if there is evidence of concomitant left ventricular dysfunction with an electrical dyssynchrony. Patients with systemic right ventricles such as post-atrial baffle surgery or congenitally corrected transposition reportedly do well with CRT in the presence of both inter-ventricular and intra-ventricular dyssynchrony. There is little doubt that moving forward to best way to identify which pediatric patients with heart failure will respond to CRT, will require a collaborative effort between the electrophysiologist and the echocardiographer to identify appropriate candidates with electrical and mechanical dyssynchrony.

Aims: Advances in medical treatment have resulted in increased life expectancy in congenital heart disease. Consequently, the focus of management has shifted from reducing mortality to reducing long-term morbidity with the goal of improving quality of life. A predictor of quality of life might be N-terminal pro-brain natriuretic peptide, a well-established marker for heart failure. We aimed to determine the association between N-terminal pro-brain natriuretic peptide and quality of life in patients with congenital heart disease. Methods: We collected blood samples from consecutive patients who were initially operated between 1968 and 1980 (47.8% women; mean age 40.2±5.4 years). The 36-item Short-Form Health Survey was completed to assess subjective health status as a measure of quality of life. Analysis was performed for the entire group and for subgroups defined as simple versus complex congenital heart diseases. Median N-terminal pro-brain natriuretic peptide level was 15.2 pmol/L (overall range 1.3–299.3 pmol/L). N-terminal pro-brain natriuretic peptide levels were associated with the subdomain physical functioning (β=−0.074, p=0.031). This association remained significant after adjustment for age and sex (β=−0.071, p=0.038) and after adjustment for age, sex, body mass index, left ventricular function, and renal function (β=−0.069, p=0.048). In complex congenital heart disease, the association between N-terminal pro-brain natriuretic peptide and physical functioning remained significant in multivariable analysis (β=−0.076, p=0.046). No associations were found in the simple congenital heart disease group or on the other health status subdomains. Conclusion: In adults operated for congenital heart disease, N-terminal pro-brain natriuretic peptide is associated with the subdomain physical, primarily in the complex subgroup.

Background: Accelerated coronary atherosclerosis in patients with Kawasaki disease, in conjunction with coronary artery aneurysm and stenosis that characterise this disease, are potential risk factors for developing coronary artery disease in young adults. We aimed to determine the prevalence and predictors of coronary artery disease in adult patients with Kawasaki disease. Methods: All patients aged 18−55 years of age diagnosed with Kawasaki disease were sampled from Nationwide Inpatient Sample database using International Classification of Diseases 9th revision (ICD 9 code 446.1) from 2009 to 2010. Demographics, prevalence of coronary artery disease, and other traditional risk factors in adult patients with Kawasaki disease were analysed using ICD 9 codes. Results: The prevalence of Kawasaki disease among adults was 0.0005% (n=215) of all in-hospital admissions in United States. The mean age was 27.3 years with women (27.6 years) older than men (27.1 years). Traditional risk factors were hypertension (21%), hyperlipidaemia (15.6%), diabetes (11.5%), tobacco use (8.8%), and obesity (8.8%), with no significant difference between men and women. Coronary artery disease (32.4%), however, was more prevalent in men (44.7%) than in women (12.1%; p=0.03). In multivariate regression analysis, after adjusting for demographics and traditional risk factors, hypertension (OR=13.2, p=0.03) was an independent risk factor of coronary artery disease. Conclusion: There was increased preponderance of coronary artery disease in men with Kawasaki disease. On multivariate analysis, hypertension was found to be the only independent predictor of coronary artery disease in this population after adjusting for other risk factors.

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.

Supravalvular aortic aneurysms are less frequent than abdominal ones. Among Supravalvular aortic aneurysm aetiologies, we focused on dystrophic lesions as they can be secondary to genetic causes such as elastin anomaly. We report on a familial 7q11.23 triplication – including the ELN gene – segregating with a supravalvular aortic aneurysm. During her first pregnancy, our index patient was diagnosed with tuberous sclerosis and with a Supravalvular aortic aneurysm. The foetus was affected equally. For the second pregnancy, parents applied for preimplantation diagnosis, and a subsequent prenatal diagnosis was offered to the couple, comprising TSC1 molecular analysis, karyotype, and multiplex ligation probe amplification. TSC1 mutation was not found on foetal deoxyribo nucleic acid. Foetal karyotype was normal, but multiplex ligation probe amplification detected a 7q11.23 duplication. Quantitative-polymerase chain reaction and array-comparative genomic hybridisation carried out to further assess this chromosome imbalance subsequently identified a 7q11.23 triplication involving ELN and LIMK1. Foetal heart ultrasound identified a Supravalvular aortic aneurysm. A familial screening was offered for the 7q11.23 triplication and, when found, heart ultrasound was performed. The triplication was diagnosed in our index case as well as in her first child. Of the 17 individuals from this family, 11 have the triplication. Of the 11 individuals with the triplication, 10 were identified to have a supravalvular aortic aneurysm. Of them, two individuals received a medical treatment and one individual needed surgery. We provide evidence of supravalvular aortic aneurysm segregating with 7q11.23 triplication in this family. We would therefore recommend cardiac surveillance for individuals with 7q11.23 triplication. It would also be interesting to offer a quantitative-polymerase chain reaction or an array-comparative genomic hybridisation to a larger cohort of patients presenting with isolated supravalvular aortic aneurysm, as it may provide further information.

Congenital anomalies of the coronary arteries, although uncommon, have the potential to cause serious myocardial damage, ischaemic cardiomyopathy, and sudden cardiac death. This article summarises aspects of care for these patients in the outpatient setting, including clinical history and physical examination findings, ancillary testing, decision-making regarding the need for surgical intervention, and recommendations for physical activity. Although there are limited data regarding some of these recommendations, it is hoped that these can be used as an initial benchmark against which further data will lead to a more evidence-based approach.

Paediatric heart transplantation has evolved over the last 3 decades. The research group, Pediatric Heart Transplant Study, has been in step with that evolution over the nearly 20 years of its existence by utilising its registry to contribute a wealth of clinical research to the field. The highlights of its studies will be presented in this review.

Congenital heart diseases are common congenital anomalies with 1% prevalence worldwide and are associated with significant childhood morbidity and mortality. Among a wide range of aetiologically heterogeneous conditions, conotruncal anomalies account for approximately one-third of all congenital heart defects. The aetiology of conotruncal heart diseases is complex, with both environmental and genetic causes. Hyperhomocysteinaemia, which is often accompanied by the defects of folic acid metabolism, is known to cause conotruncal heart anomalies. In this study, we have evaluated three polymorphisms in the following two hyperhomocysteinaemia-related genes: methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and nicotinamide N-methyl transferase (NNMT rs694539) in 79 children with conotruncal heart disease and 99 children without conotruncal heart disease. Genotype distribution of the MTHFR A1298C polymorphism showed a statistically significant difference between the two groups. In the case group, AC and CC genotypes were higher than the control group (p<0.05). We have found that MTHFR A1298C polymorphism is associated with conotruncal heart disease; C allele (p=0.028), AC (OR[95% CI]=2.48[1.24–4.95], p=0.010), CC (OR[95% CI]=3.01[1.16–7.83], p=0.023), and AC+CC (OR[95% CI]=2.60[1.36–4.99], p=0.004) genotypes are more frequent in the patient group. Genotype distributions of the MTHFR C677T and NNMT rs694539 polymorphisms were similar in the two groups when evaluated separately and also according to the dominant genetic model (p>0.05). Our results suggest that MTHFR 1298C allele is a risk factor for conotruncal heart disease.

Background: Anthracyclines are effective medications for childhood cancer. Their limitation is the risk of cardiomyopathy. Although diastolic dysfunction has been described in patients who received anthracyclines, cardiac monitoring has focused on systolic function, which is abnormal in up to 41% of the patients. We conducted a study to assess diastolic function utilising transmitral inflow Doppler velocities and tissue Doppler imaging in anthracycline-treated children 5 years post-therapy. Methods: This was a retrospective study on 63 anthracycline-treated patients. Echocardiographic parameters included peak early and late transmitral inflow Doppler velocities (E, A), E/A ratio, E deceleration time, and tissue Doppler imaging early and late diastolic mitral annulus velocities (E′, A′), E/E′ ratio, and E′/A′ ratio. Results: All indices of diastolic function that we measured were normal in the anthracycline-treated patients. Conclusion: We conclude that diastolic function assessed by transmitral inflow Doppler velocities and tissue Doppler imaging is normal in anthracycline-treated children 5 years after completion of treatment. Further longitudinal study is needed to determine whether diastolic function becomes abnormal with time in this patient population.

Objective: The objective of the study was to analyse the use of the pressure wire for the acquisition of intravascular pulmonary pressures in the presence of pulmonary atresia and systemic-dependent pulmonary blood flow. Methods: In this study, we included patients with pulmonary atresia and systemic-dependent pulmonary circulation referred for diagnostic catheterisation for evaluation of pulmonary pressures during the period from April, 2012 to April, 2013. The systemic-pulmonary collateral arteries were selectively catheterised, and in the absence of a critical stenosis angiographically determined; the pressure wire was introduced in these arteries to reach the main pulmonary artery, and/or lobar, and segmental branches. Aortic and pulmonary pressures were simultaneously obtained. We evaluated the feasibility and safety of the method. Results: We studied 10 patients (age 21 days to 11 years). In all of them, the pressures of pulmonary circulation – main artery, and/or lobar, and segmental branches – were successfully measured with the pressure wire. Of eight patients with indication for Rastelli surgery, the pulmonary pressures were considered normal in five, and slightly increased in three. In two patients requiring univentricular correction – total cavopulmonary anastomosis – the diastolic pressure was increased (20 mmHg). All procedures were performed without haemodynamic instability, cardiac arrhythmia, systemic saturation reduction, death, or any other complication. Conclusion: Measurement of pulmonary vascular pressures using the pressure wire in small patients with pulmonary atresia is safe and effective. It allows the acquisition of reliable pressure curves, even in the presence of small vessels, bending and tortuosity, without the risk usually associated with the use of conventional diagnostic catheters.

Background: The term “borderline left ventricle” describes a small left heart that may be inadequate to provide systemic cardiac output and implies the potential need for a single-ventricle palliation. The aim of this study was to identify foetal echocardiographic features that help discriminate which infants will undergo single-ventricle palliation versus biventricular repair to aid in prenatal counselling. Methods: The foetal database at our institution was searched to identify all foetuses with borderline left ventricle, as determined subjectively by a foetal cardiologist, from 2000 to 2011. The foetal images were retrospectively analysed for morphologic and physiologic features to determine which best predicted the postnatal surgical choice. Results: Of 39 foetuses identified with borderline left ventricle, 15 were planned for a univentricular approach, and 24 were planned for a biventricular approach. There were significant differences between the two outcome groups in the Z-scores of the mitral valve annulus, left ventricular end-diastolic dimension, aortic valve annulus, and ascending aorta diameter (p<0.05). With respect to discriminating univentricular outcomes, cut-offs of mitral valve Z-score ⩽−1.9 and tricuspid:mitral valve ratio ⩾1.5 were extremely sensitive (100%), whereas a right:left ventricular end-diastolic dimension ratio ⩾2.1 provided the highest specificity (95.8%). Conclusion: In foetuses with borderline left ventricle, a mitral valve Z-score ⩾−1.9 or a tricuspid:mitral valve ratio ⩽1.5 suggests a high probability of biventricular repair, whereas a right:left ventricular end-diastolic dimension ratio ⩾2.1 confers a likelihood of single-ventricle palliation.

Introduction: Cyanotic congenital heart disease is associated with functional limitation and vascular events. The nature and extent of endothelial dysfunction in cyanotic adults is poorly understood. We sought to characterise endothelial function in this setting. Methods: A total of fourteen adults with cyanotic congenital heart disease (40±3 years) together with age- and sex-matched healthy controls underwent assessment of nitric oxide-dependent vascular responses, including flow-mediated dilatation of the brachial artery and dynamic vessel analysis of the retina in response to flickering light. Plasma levels of the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial progenitor cells were assessed by flow cytometry. Results: Flow-mediated dilatation was significantly lower in cyanosed adults than controls (4.0±0.8 versus 7.2±1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory responses were also impaired (2.9±0.8 versus 5.0±0.6%, p=0.05 and 3.4±0.3 versus 5.2±0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric dimethylarginine were higher in cyanosed adults (3.0±0.6 versus 1.1±0.1 pg/ml, p=0.004 and 0.68±0.05 versus 0.52±0.02 μmol/L, p=0.03, n=11). Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with chronic cyanosis (17±4 versus 40±6 per million white blood cells, p=0.005, n=11). Conclusions: Endothelial function is impaired in the systemic arteries and retinal vessels in adults with cyanotic congenital heart disease, suggesting a widespread endotheliopathy. Diminished numbers of endothelial progenitor cells might potentially contribute to these observations.

The aims of this study were to assess the development of heart failure in patients with congenitally corrected transposition of the great arteries in a medium-term follow-up, to identify the impact of tricuspid regurgitation on the development of heart failure, and to determine the most reliable marker for its identification. The prospective 6-year follow-up study included 19 adult patients. All patients were evaluated clinically by the determination of N-terminal pro-hormone brain natriuretic peptide levels, exercise stress testing, echocardiography magnetic resonance, or CT. Among them, two patients died of heart failure. There was a decline in exercise capacity and systolic systemic ventricular function (p=0.011). Systemic ventricular ejection fraction decreased (48.3±13.7 versus 42.7±12.7%, p=0.001). Tissue Doppler imaging showed a decline in peak tricuspid systolic annular velocity (10.3±2.0 versus 8.3±2.5 cm/second, p=0.032) and peak tricuspid early diastolic annular velocity (14.6±4.3 versus 12.0±4.5 cm/second, p=0.048). The tricuspid regurgitation did not increase significantly. N-terminal pro-hormone brain natriuretic peptide levels increased (127.0 ng/L(82.3–305.8) versus 226.0 ng/L(112.5–753.0), p=0.022). Progressive exercise intolerance in congenitally corrected transposition of the great arteries appears to be driven mainly by a progression in systemic right ventricular dysfunction. Tricuspid regurgitation is likely to play a role, especially in patients with structural abnormalities of the tricuspid valve – Ebstein anomaly. The N-terminal pro-hormone brain natriuretic peptide levels and tissue Doppler parameters appear sensitive in detecting changes over time and may guide management.