Auscultation While Standing: A Basic and Reliable Method to Rule Out a Pathologic Heart Murmur in Children.

PURPOSE: The distinction between physiologic (innocent) and pathologic (organic) heart murmurs is not always easy in routine practice, leading too often to unnecessary cardiology referrals and expensive investigations. We aimed to test the hypothesis that the complete disappearance of murmur on standing can exclude cardiac disease in children. METHODS: From January 2014 to January 2015, we prospectively included 194 consecutive children aged 2 to 18 years who were referred for heart murmur evaluation to pediatric cardiologists at 2 French medical centers. Heart murmur characteristics while supine and then while standing were recorded, and an echo-cardiogram was performed. RESULTS: Overall, 30 (15%) of the 194 children had a pathologic heart murmur as determined by an abnormal echocardiogram. Among the 100 children (51%) who had a murmur that was present while they were supine but completely disappeared when they stood up, only 2 had a pathologic murmur, and just 1 of them needed further evaluation. Complete disappearance of the heart murmur on standing therefore excluded a pathologic murmur with a high positive predictive value of 98% and specificity of 93%, albeit with a lower sensitivity of 60%. CONCLUSIONS: Disappearance of a heart murmur on standing is a reliable clinical tool for ruling out pathologic heart murmurs in children aged 2 years and older. This basic clinical assessment would avoid many unnecessary referrals to cardiologists.

Barth syndrome in a female patient.

BACKGROUND: Barth syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy, skeletal myopathy and cyclic neutropenia in male patients. It is caused by mutations in the TAZ gene coding for the tafazzin, a protein involved in the remodeling of cardiolipin. Loss of cardiolipin in the inner mitochondrial membrane results in respiratory chain dysfunction. No specific symptom has been identified in female carriers. CASE REPORT: We report the first case of BTHS confirmed by TAZ gene analysis in a female patient. This girl experienced severe heart failure at 1-month of age. Echocardiography diagnosed dilated-hypokinetic and hypertrophic cardiomyopathy with noncompaction of the left ventricle. Initial metabolic screening was normal, except for a cyclic neutropenia. Respiratory chain analysis performed on skin fibroblasts revealed a decreased activity of complexes I, III and IV. Screening on a bloodspot showed abnormal monolysocardiolipin:cardiolipin ratio, later confirmed on cultured fibroblasts, indicative of BTHS. Genetic analyses finally confirmed the diagnosis of BTHS, by showing a large intragenic deletion of exons 1 through 5 in the TAZ gene. Cytogenetic analysis showed mosaicism for monosomy X and for a ring X chromosome with a large deletion of the long arm including the Xq28 region. The girl presented recurrent episodes of severe acute heart failure, progressive muscle weakness, and had a fatal septic shock at 3 years. CONCLUSION: This case highlights that the diagnosis of BTHS should also be suspected in female patients presenting a phenotype similar to affected boys. In these cases, analysis of the monolysocardiolipin:cardiolipin ratio in bloodspots is a rapid and sensitive screening tool for BTHS. However clinical expression in a carrier female requires hemizygosity for the mutated allele of the TAZ gene, which supposes a rearrangement of the TAZ gene region on the other X chromosome.

Natural history of Barth syndrome: a national cohort study of 22 patients.

BACKGROUND: This study describes the natural history of Barth syndrome (BTHS). METHODS: The medical records of all patients with BTHS living in France were identified in multiple sources and reviewed. RESULTS: We identified 16 BTHS pedigrees that included 22 patients. TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2-2.3). The median age at presentation was 3.1 weeks (range, 0-1.4 years), and the median age at last follow-up was 4.75 years (range, 3-15 years). Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients ≥3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (<0.5 × 109/L) and birth year. Specifically, the survival rate was 70% for patients born after 2000 and 20% for those born before 2000. CONCLUSIONS: This survey found that BTHS outcome was affected by cardiac events and by a risk of infection that was related to neutropenia. Modern management of heart failure and prevention of infection in infancy may improve the survival of patients with BTHS without the need for heart transplantation.

Unusual hemodynamic changes in an infant with a restrictive ventricular septal defect.

A 7-month-old asymptomatic infant was known to have a restrictive membranous ventricular septal defect partially closed by an aneurysm of the membranous septum. At 13 months of age, he developed unexpected pulmonary hypertension, with no clinical sign of cardiac failure. Cardiac catheterization assessed the pulmonary artery pressure at a systemic level with significant left-to-right shunt. After surgical closure, the pulmonary arterial pressure decreased by 50%. We suspect an enlargement of the ventricular septal defect caused by the rupture of the aneurysm of the membranous septum-a rare complication.