Prenatal physiologic findings and postnatal advanced imaging in the management of absent pulmonary valve syndrome with intact ventricular septum.

Absent pulmonary valve syndrome is a congenital heart defect usually associated with tetralogy of Fallot. Rarely, absent pulmonary valve syndrome can occur independently of tetralogy of Fallot and presents with an intact ventricular septum and a patent ductus arteriosus. This case report describes the prenatal diagnosis of absent pulmonary valve syndrome with intact ventricular septum via echocardiogram and the postnatal management of the resulting physiologic effects secondary to this rare congenital heart disease.

Intravenous sotalol use in a complex critically ill child: balancing the systems in choosing antiarrhythmic medication.

In critically ill children, multi-organ-system disease can influence the choice of antiarrhythmic medication. Intravenous therapy is often necessary. There is a scarcity of paediatric critical-care cases demonstrating the dosing, monitoring, and efficacy of intravenous sotalol. This case demonstrates the effective use of intravenous sotalol in an adolescent with renal, hepatic, and haematological dysfunctions.

Mutations in PDLIM5 are rare in dilated cardiomyopathy but are emerging as potential disease modifiers.

BACKGROUND: A causal genetic mutation is found in 40% of families with dilated cardiomyopathy (DCM), leaving a large percentage of families genetically unsolved. This prevents adequate counseling and clear recommendations in these families. We aim to identify novel genes or modifiers associated with DCM. METHODS: We performed computational ranking of human genes based on coexpression with a predefined set of genes known to be associated with DCM, which allowed us to prioritize gene candidates for their likelihood of being involved in DCM. Top candidates will be checked for variants in the available whole-exome sequencing data of 142 DCM patients. RNA was isolated from cardiac biopsies to investigate gene expression. RESULTS: PDLIM5 was classified as the top candidate. An interesting heterozygous variant (189_190delinsGG) was found in a DCM patient with a known pathogenic truncating TTN-variant. The PDLIM5 loss-of-function (LoF) variant affected all cardiac-specific isoforms of PDLIM5 and no LoF variants were detected in the same region in a control cohort of 26,000 individuals. RNA expression of PDLIM5 and its direct interactors (MYOT, LDB3, and MYOZ2) was increased in cardiac tissue of this patient, indicating a possible compensatory mechanism. The PDLIM5 variant cosegregated with the TTN-variant and the phenotype, leading to a high disease penetrance in this family. A second patient was an infant with a homozygous 10 kb-deletion of exon 2 in PDLIM5 resulting in early-onset cardiac disease, showing the importance of PDLIM5 in cardiac function. CONCLUSIONS: Heterozygous PDLIM5 variants are rare and therefore will not have a major contribution in DCM. Although they likely play a role in disease development as this gene plays a major role in contracting cardiomyocytes and homozygous variants lead to early-onset cardiac disease. Other environmental and/or genetic factors are probably necessary to unveil the cardiac phenotype in PDLIM5 mutation carriers.

The role of regional prenatal cardiac screening for congenital heart disease: A single center experience.

BACKGROUND: Accurate prenatal diagnosis of congenital heart disease (CHD) allows for appropriate delivery and postnatal management. Geographic constraints limit access to fetal cardiology subspecialists. In our approach, general pediatric cardiologists are first line in regional prenatal cardiac screening. We aim to demonstrate the utility of this approach in diagnosing CHD requiring cardiac interventions within 30 days of life. METHODS: This is a retrospective review of fetal echocardiograms performed at Seattle Children's Hospital regional cardiology sites (SCH-RC) from December 2008 to December 2015. Referrals to Seattle Children's Hospital Prenatal Program (SCH-PNP) were evaluated for referral timing, indication, diagnostic accuracy, and postnatal care. Diagnostic accuracy was determined using the initial postnatal echocardiogram as the gold standard. Major discrepancy was defined as one resulting in change in surgical management. RESULTS: Of 699 fetuses evaluated at regional sites throughout Washington and Alaska, a small subset (n = 48; 6.9%) required referral to SCH-PNP. Need for relocation was confirmed in 31 subjects, of which 27 required cardiac intervention within 30 days of life. Of those not referred to SCH-PNP (n = 643, 91.9%), none required neonatal cardiac intervention. There were 22 regional diagnostic discrepancies (31% major, 7% minor). Referral to SCH-PNP improved diagnostic accuracy (2% major, 0% minor). CONCLUSIONS: Regional prenatal cardiac screening demonstrated 100% sensitivity and 98.9% specificity for identifying critical CHD. Utilizing regional pediatric cardiologists as first line in prenatal screening in geographically remote regions may improve access to care and outcomes in neonates with critical CHD while improving resource utilization.