Clinical and Genetic Screening for Hypertrophic Cardiomyopathy in Paediatric Relatives: Changing Paradigms in Clinical Practice.

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality in children. While the aetiology is heterogeneous, most cases are caused by variants in the genes encoding components of the cardiac sarcomere, which are inherited as an autosomal dominant trait. In recent years, there has been a paradigm shift in the role of clinical screening and predictive genetic testing in children with a first-degree relative with HCM, with the recognition that phenotypic expression can, and often does, manifest in young children and that familial disease in the paediatric age group may not be benign. The care of the child and family affected by HCM relies on a multidisciplinary team, with a key role for genomics. This review article summarises current evidence in clinical and genetic screening for hypertrophic cardiomyopathy in paediatric relatives and highlights aspects that remain to be resolved.

Ten Years of Percutaneous Pulmonary Valve Implantation in Australia and New Zealand.

OBJECTIVE: This study sought to investigate the characteristics, morbidity (including the rate of infective endocarditis and valve replacement) and mortality of individuals undergoing percutaneous pulmonary valve implantation in Australia and New Zealand since the procedure has been performed. BACKGROUND: The outcomes of percutaneous pulmonary valve implantation in Australia and New Zealand have not been evaluated. Recent international data, including patients from New Zealand, suggests the rate of infective endocarditis is not insignificant. METHODS: A retrospective multi-site cohort study was undertaken via medical record review at the centres where percutaneous pulmonary valve implantation has been performed. All procedures performed from 2009-March 2018 were included. Individuals were identified from local institution databases. Data was collected and analysed including demographics, details at the time of intervention, haemodynamic outcome, post procedure morbidity and mortality. Multi-site ethics approval was obtained. RESULTS: One hundred and seventy-nine (179) patients attended the cardiac catheter laboratory for planned percutaneous pulmonary valve implantation. Of these patients, 172 underwent successful implantation. Tetralogy of Fallot and pulmonary atresia were the most common diagnoses. The median age at procedure was 19 years (range 3-60 yrs). There was a significant improvement in the acute haemodynamics in patients undergoing percutaneous pulmonary valve implantation for stenosis. Seven (7) patients (3.9%) experienced a major procedural/early post procedure complication (death, conversion to open procedure, cardiac arrest), including two deaths. The annualised rates of infective endocarditis and valve replacement were 4.6% and 3.8% respectively. There was one death related to infective endocarditis in follow-up. CONCLUSIONS: Percutaneous pulmonary valve replacement is a relatively safe method of rehabilitating the right ventricular outflow tract.

Life-threatening cardiac arrhythmia and sudden death during electronic gaming: An international case series and systematic review.

BACKGROUND: Electronic gaming has recently been reported as a precipitant of life-threatening cardiac arrhythmia in susceptible individuals. OBJECTIVE: The purpose of this study was to describe the population at risk, the nature of cardiac events, and the type of game linked to cardiac arrhythmia associated with electronic gaming. METHODS: A multisite international case series of suspected or proven cardiac arrhythmia during electronic gaming in children and a systematic review of the literature were performed. RESULTS: Twenty-two patients (18 in the case series and 4 via systematic review; aged 7-16 years; 19 males [86%]) were identified as having experienced suspected or proven ventricular arrhythmia during electronic gaming; 6 (27%) had experienced cardiac arrest, and 4 (18%) died suddenly. A proarrhythmic cardiac diagnosis was known in 7 (31%) patients before their gaming event and was established afterward in 12 (54%). Ten patients (45%) had catecholaminergic polymorphic ventricular tachycardia, 4 (18%) had long QT syndrome, 2 (9%) were post-congenital cardiac surgery, 2 (9%) had "idiopathic" ventricular fibrillation, and 1 (after Kawasaki disease) had coronary ischemia. In 3 patients (14%), including 2 who died, the diagnosis remains unknown. In 13 (59%) patients for whom the electronic game details were known, 8 (62%) were war games. CONCLUSION: Electronic gaming can precipitate lethal cardiac arrhythmias in susceptible children. The incidence appears to be low, but syncope in this setting should be investigated thoroughly. In children with proarrhythmic cardiac conditions, electronic war games in particular are a potent arrhythmic trigger.

School-Age Developmental and Educational Outcomes Following Cardiac Procedures in the First Year of Life: A Population-Based Record Linkage Study.

The purpose of the study was to evaluate school-age developmental and educational outcomes for children with and without a cardiac procedure in the first year of life to improve understanding of longer-term neurodevelopmental outcomes in children who have had a cardiac procedure for congenital heart disease, the most common serious congenital anomaly. A population-based cohort study using record linkage of state-wide data was undertaken, evaluating children born in New South Wales, Australia, 2001-2007. Those with and without a cardiac procedure in the first year of life with a linked developmental (Australian version Early Development Instrument testing result, age 4-6 years) and/or educational outcome (Australian National Assessment Program result, age 7-9 years) were included. Perinatal, perioperative and sociodemographic factors were examined using multivariable logistic regression models. Of 468,329 eligible children, 768 had a cardiac procedure in the first year of life and 582 were included. For those with a cardiac procedure and developmental outcome (n = 260), 13.1% were classified as having 'special needs' compared to 4.4% without a cardiac procedure. Of those with an educational outcome, after adjusting for perinatal, perioperative and demographic variables, children with a cardiac procedure (n = 396) were twice as likely to score below National Minimum Standard in school literacy and numeracy tests compared to their peers. Significant predictors included low birthweight, parent not completing school and having > 4 re-hospitalisations in their first six years. The developmental and educational trajectory of children who have had a cardiac procedure in their first year remains altered into primary school years. While perioperative factors did not impact outcomes, ongoing health and sociodemographic factors were important in identifying those children at greatest risk.

4D flow magnetic resonance imaging: role in pediatric congenital heart disease.

Imaging-based evaluation of cardiac structure and function remains paramount in the diagnosis and monitoring of congenital heart disease in childhood. Accurate measurements of intra- and extracardiac hemodynamics are required to inform decision making, allowing planned timing of interventions prior to deterioration of cardiac function. Four-dimensional flow magnetic resonance imaging is a nonionizing noninvasive technology that allows accurate and reproducible delineation of blood flow at any anatomical location within the imaging volume of interest, and also permits derivation of physiological parameters such as kinetic energy and wall shear stress. Four-dimensional flow is the focus of a great deal of attention in adult medicine, however, the translation of this imaging technique into the pediatric population has been limited to date. A more broad-scaled application of 4-dimensional flow in pediatric congenital heart disease stands to increase our fundamental understanding of the cause and significance of abnormal blood flow patterns, may improve risk stratification, and inform the design and use of surgical and percutaneous correction techniques. This paper seeks to outline the application of 4-dimensional flow in the assessment and management of the pediatric population affected by congenital heart disease.

Mortality, rehospitalizations and costs in children undergoing a cardiac procedure in their first year of life in New South Wales, Australia.

BACKGROUND: Cardiac procedures are part of management for many children with congenital heart disease (CHD). Using population health data, this study explores health outcomes of children undergoing a cardiac procedure in the first year of life to better understand the impact of CHD on children, families and health services. METHODS AND RESULTS: A population-based record-linkage cohort study was undertaken. Rate of cardiac procedures in the first year of life over the study period 2001-2012 in New South Wales, Australia, was steady at 2.5 children per 1000 live births, accounting for 2722 children. Excluding those with isolated closure of patent ductus arteriosus (n=416), 50% required readmission in the first year of life. Over 1/5th had an additional non-cardiac congenital anomaly. Average total cost per infant for initial procedure admission was $67,054 AUD ($63,124-$70,984) with a median length of stay (LOS) 13days (IQR 8-23). Average cost per readmission in the first year of life was $11,342 (95% CI 10,361-$12,323) with median LOS 2days (IQR 1-5). Mortality rate in the 30days following initial procedure was 3.1% (72/2306). Mortality rate by age 1year was 7.1%, and 13.8% for those who had neonatal surgery. CONCLUSION: Risk of mortality in operatively-managed CHD extends beyond the immediate perioperative period. Children undergoing a cardiac procedure in their first year are often readmitted to hospital for both further planned procedures and unplanned reasons such as infection. These readmissions capture the significant impact of illness and pose substantial financial cost to the health system.

Health outcomes of infants born to women with heart valve prostheses: complications of prematurity alone?

The health outcomes of children born to women with heart valve prostheses in New South Wales, Australia, 2000-2011, were examined in a record-linkage population-based study. Eighty-one women delivered 112 infants. One infant was stillborn, two died prior to discharge from hospital. Twenty seven (24.8%) were readmitted to hospital in their first year of life. The average number of readmissions up to age 6 years was 2.7 (95% CI 1.51-3.89) versus population rate of 2.04 (95% CI 2.03-2.05). The children demonstrated an increased risk of adverse event in the first year of life. Reassuringly however, and not previously reported, mortality and health outcomes in the first 6 years of life were not significantly different to the general population.

Heart valve prostheses in pregnancy: outcomes for women and their infants.

BACKGROUND: As the prognosis of women with prosthetic heart valves improves, an increasing number are contemplating and undertaking pregnancy. Accurate knowledge of perinatal outcomes is essential, assisting counseling and guiding care. The aims of this study were to assess outcomes in a contemporary population of women with heart valve prostheses undertaking pregnancy and to compare outcomes for women with mechanical and bioprosthetic prostheses. METHODS AND RESULTS: Longitudinally linked population health data sets containing birth and hospital admissions data were obtained for all women giving birth in New South Wales, Australia, 2000-2011. This included information identifying presence of maternal prosthetic heart valve. Cardiovascular and birth outcomes were evaluated. Among 1 144 156 pregnancies, 136 involved women with a heart valve prosthesis (1 per 10 000). No maternal mortality was seen among these women, although the relative risk for an adverse event was higher than the general population, including severe maternal morbidity (139 versus 14 per 1000 births, rate ratio [RR]=9.96, 95% CI 6.32 to 15.7), major maternal cardiovascular event (44 versus 1 per 1000, RR 34.6, 95% CI 14.6 to 81.6), preterm birth (183 versus 66 per 1000, RR=2.77, 95% CI 1.88 to 4.07), and small-for-gestational-age infants (193 versus 95 per 1000, RR=2.03, 95% CI 1.40 to 2.96). There was a trend toward increased maternal and perinatal morbidity in women with a mechanical valve compared with those with a bioprosthetic valve. CONCLUSIONS: Pregnancies in women with a prosthetic heart valve demonstrate an increased risk of an adverse outcome, for both mothers and infants, compared with pregnancies in the absence of heart valve prostheses. In this contemporary population, the risk was lower than previously reported.

Prosthetic heart valves in pregnancy: a systematic review and meta-analysis protocol.

BACKGROUND: Advances in surgical technique, prosthetic heart valve design, and anticoagulation have contributed to an overall improvement in morbidity and mortality in women with heart valve prostheses as well as increased feasibility of pregnancy. Previous work investigating the pregnancies of women with prosthetic valves has been directed largely toward understanding the influence of anticoagulation regimen. There has been little investigation on maternal and infant outcomes. The objective of this systematic review will be to assess the outcomes of pregnancy in women with heart valve prostheses in contemporary populations. METHODS/DESIGN: A systematic search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library will be undertaken. Article titles and abstracts will be evaluated by two reviewers for potential relevance. Studies that include pregnancies occurring from 1995 onwards and where there are six or more pregnancies in women with heart valve prostheses included in the study population will be reviewed for potential inclusion. Primary outcomes of interest will be mortality (maternal and perinatal). Secondary outcomes will include other pregnancy outcomes. No language restrictions will be applied. Methodological quality and heterogeneity of studies will be assessed. Data extraction from identified articles will be undertaken by two independent reviewers using a uniform template. Meta-analyses will be performed to ascertain risk of adverse events and, where numbers are sufficient, by type of prosthesis and location as well as other subgroup analyses. DISCUSSION: Estimates of the risk of adverse events in recent pregnancies of women with heart valve prosthesis will provide better information for counselling and decision making. Given the improvements in prognosis of heart valve prosthesis recipients and the paucity of definitive data regarding optimal pregnancy management for these women, review of this topic is pertinent. REVIEW REGISTRATION: This protocol has been registered with the international prospective register of systematic reviews (PROSPERO) as number CRD42013006187, accessible online at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013006187#.Utk7qNJ9Lf8.