The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death.

There is an incomplete understanding of the burden of splice-disrupting variants in definitively associated inherited heart disease genes and whether these genes can amplify from blood RNA to support functional confirmation of splicing outcomes. We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue.

loss-of-function variants in families with left ventricular non-compaction cardiomyopathy.

encodes a cardiac transcription factor that is associated with atrial septal defects. Recent studies implicate loss-of-function variants with left ventricular non-compaction cardiomyopathy (LVNC), although clinical and genetic data in families are limited. We report four families with loss-of-function variants that segregate with LVNC.

Genetic Basis of Childhood Cardiomyopathy.

Background: The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members.

Methods: We recruited children from a pediatric cardiology service or genetic heart diseases clinic.

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

Aims: The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events.

"Will she live a long happy life?" Parents' concerns for their children with Fontan circulation.

Background: Families of children at the worst end of the congenital heart disease endure a significant burden which is often not clearly delineated in the clinical literature. We examined the greatest concerns of parents whose children have a Fontan circulation.

Methods: Parents ( = 107) of children in the Australian and New Zealand Fontan Registry completed online surveys with open-ended and closed questions.

"How long will I continue to be normal?" Adults with a Fontan circulation's greatest concerns.

Background: Little is known about adults living with a Fontan circulation's concerns outside the scope of their clinical outcomes. We examined adults with a Fontan circulations' greatest concerns, as well as their concerns around anti-coagulation, pregnancy and finances.

Methods: Adults with a Fontan circulation in the Australian and New Zealand Fontan Registry were invited to complete an anonymous online survey, of which 57 participated.

Long-Term Outcomes of Childhood Left Ventricular Noncompaction Cardiomyopathy: Results From a National Population-Based Study.

Background: Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study.

Methods: The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study.

Background: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy.

Methods: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0-10 years of age) diagnosed with cardiomyopathy between 1987 and 1996.

Fertility and pregnancy in the Fontan population.

Background: Women with a Fontan circulation are deemed at significantly increased risk of maternal morbidity and mortality during pregnancy. Publications describe a small number of pregnancies worldwide and a high rate of miscarriage. We compiled the experience of women enrolled in the Australia and New Zealand Fontan (ANZ) Registry with regard to menarche, contraceptive use, pregnancy advice and pregnancy outcomes.

Sudden death in childhood cardiomyopathy: results from a long-term national population-based study.

Background: Children with cardiomyopathy (CM) are at risk of sudden cardiac death (SCD), but the incidence and risk factors for this outcome are not clear.

Objectives: This study sought to determine the incidence and risk factors for SCD in children with varying CM phenotypes from a long-term population-based study of childhood CM.

Methods: The NACCS (National Australian Childhood Cardiomyopathy Study) is an ongoing longitudinal cohort study including all children in Australia with primary CM who were diagnosed between January 1, 1987, and December 31, 1996, and were <10 years of age.

Anticoagulation of cardiomyopathy in children.

Objectives: Cardiomyopathy is a common cause of heart failure in children. Thrombosis is a potential significant secondary complication. Thus warfarin is recommended by the American College of Chest Physicians for the treatment of children with cardiomyopathy despite the lack of published evidence to support its use.

Long-term outcomes of dilated cardiomyopathy diagnosed during childhood: results from a national population-based study of childhood cardiomyopathy.

Background: Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy.

Methods And Results: The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings.

Sympathetic and vascular dysfunction in adult patients with Fontan circulation.

Background: Patients with Fontan circulation are known to have increased systemic vascular resistance (SVR) however the underlying mechanisms are uncertain. We therefore further investigated the haemodynamic and vascular profile of Fontan patients.

Methods: Eighteen adult subjects aged 25 ± 1 years who had undergone the Fontan procedure in their childhood (at age 6 ± 1 years) and not in clinical failure at the time of study were assessed for: 1) autonomic function, including direct muscle sympathetic nerve activity (MSNA) recording and sympathetic and cardiac baroreflex function, 2) endothelial function by means of reactive hyperaemia using the Endopat peripheral arterial tonometry (PAT) technique and plasma endothelin concentration and gene expression, 3) pulse wave reflections (digital and central augmentation index (AI)) and 4) haemodynamic changes to head-up tilt.

Role transition from mental health nurse to IAPT high intensity psychological therapist.

Background: The Improving Access to Psychological Therapies (IAPT) initiative has depended on the training of a new NHS mental health workforce. At step 3 of the stepped care model, capacity building has required the recruitment of a wide range of mental health professionals into high intensity therapists training posts. This shift naturally entails role transition on the part of trainees into delivering cognitive behavioural psychotherapy (CBP), but no previous research has examined the experience of such transitions.