Large Apical Muscular Ventricular Septal Defect: Asymptomatic due to Anomalous Muscle Bundles in the Right Ventricle

This case report demonstrated an apical muscular ventricular septal defect (VSD) that was a large defect but behaved like a small defect because of the restrictive flow across the anomalous muscle bundles in the right ventricular (RV) apex. The anomalous muscle bundles separated the RV sinus into two parts: the RV apex connecting with the left ventricle through the apical muscular VSD on one side, and the rest of the RV sinus connecting with RV inflow and RV outflow on the other side. These findings explained why the 11-year-old girl in this study remained asymptomatic without evidence of volume load. Thus far, it was not necessary to close her defect because of the hemodynamic insignificance.     

Renal Calculi Complicating Short‐term Furosemide Therapy after Congenital Heart Surgery

Background. Renal calcification is a known complication of Furosemide therapy. Methods. We describe 3 children who were diagnosed with renal calculi, not nephrocalcinosis, following the use of Furosemide for 4 weeks. All the infants (24, 18, and 8 months) had successful repair/palliation of congenital heart disease. The dose of Furosemide was 1–2 mg/kg/day and the duration between starting treatment and development of hematuria was 4 weeks. Results. In all 3 patients renal ultrasound confirmed the presence of renal calculi with no nephrocalcinosis. On follow‐up, hematuria improved after 3–4 months. Conclusion. Renal calculi can complicate short‐term Furosemide treatment in children after repair of congenital heart disease. Patients on Furosemide should be closely monitored by urine analysis and/or urine calcium/creatinine ratio for early detection of this complication.     

Moderate Altitude Increases Right Ventricular Pressure and Oxygen Desaturation in Adolescents with Surgically Closed Septal Defect

Objectives. Abnormal right ventricular systolic pressure response (RVPR) during exercise has previously been demonstrated in patients with septal defects of the heart. Our study investigated whether moderate altitude affects RVPR and oxygen saturation during rest and exercise in patients with surgically closed septal defects. Design. Ten patients with surgically closed heart septal defects (six secundum atrial septal defects, four ventricular septal defects) were examined by cardiopulmonary exercise testing and by echocardiography at rest and during supine cycling at sea level. After 2 hours in a hypobaric chamber at 2500 m/8200 ft altitude, exercise echocardiography was repeated. Results. During sea level exercise four patients showed abnormal RVPR (>50 mm Hg). Acute hypoxic exposure led to right ventricular systolic pressure increase above 40 mm Hg in two patients. During altitude exercise seven patients showed abnormal RVPR. Average maximal right ventricular systolic pressure was 56.5 ± 12.7 mm Hg and average for the lowest oxygen saturation was 80.0 ± 5.7%. Two patients had simultaneous oxygen desaturation below 80% and right ventricular systolic pressure above 50 mm Hg. Conclusions. Moderate altitude affects right ventricular systolic pressure and oxygen saturation in adolescents with surgically closed ventricular or atrial septal defects. Moderate altitude may induce or aggravate abnormal RVPR and oxygen desaturation during exercise in these patients.     

Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

Background

Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations.

Objectives

Investigate gene copy number variation (CNV) in children with conotruncal heart defect.

Methods

Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated.

Results

Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents.

Conclusions

Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.     

A Trileaflet “Mitral Valve” with Three Papillary Muscles: Brand New Echocardiographic Finding

Congenital mitral valve malformations are rare, but are well known and described entities. Mitral valve malformations involve mitral valve apparatuses (leaflets and annulus) and subvalvar apparatuses (chordae and papillary muscle). Case reports of accessory mitral leaflets were already described, but were usually an appendix of the normal valve. We describe here a case report and present the images of a trileaflet mitral valve sustained by three papillary muscles in a young girl with subaortic stenosis.     

Patients with Pulmonary Hypertension Related to Congenital Systemic‐to‐Pulmonary Shunts are Characterized by Inflammation Involving Endothelial Cell Activation and Platelet‐mediated Inflammation

Objective. We examined inflammatory mediators in patients with pulmonary hypertension related to congenital systemic‐to‐pulmonary shunts and the change in these markers during treatment with bosentan. Background. Inflammatory mechanisms probably play a pathogenic role in idiopathic pulmonary arterial hypertension. Their involvement in pulmonary hypertension related to congenital systemic‐to‐pulmonary shunts is largely unknown. Patients and Methods. Plasma levels of several inflammatory mediators were determined by enzyme immunoassays in 14 children and adolescents with pulmonary hypertension related to congenital systemic‐to‐pulmonary shunts before and after 12 months treatment with bosentan, and compared with levels in 54 healthy controls. Results. The patients were characterized by increased plasma levels of von Willebrand factor (～2.5‐fold), C‐reactive protein (～3.5‐fold), and soluble CD40 ligand (～2.5‐fold) as compared with controls, representing markers of endothelial cell activation, systemic inflammation, and platelet‐mediated inflammation, respectively. Patients also had significantly elevated plasma levels of osteoprotegerin (～1.6‐fold). Within the study group, N‐terminal pro‐brain natriuretic peptide levels correlated significantly with the concentrations of C‐reactive protein (r= 0.61, P < .027) and von Willebrand factor (r= 0.74, P= .004). Except for a decline in monocyte chemoattractant protein‐1 and receptor activator of nuclear factor‐κB ligand, bosentan therapy did not attenuate the systemic inflammation. Conclusion. Children and adolescents with pulmonary hypertension related to congenital systemic‐to‐pulmonary shunts are characterized by enhanced systemic inflammation involving increased endothelial cell activation and platelet‐mediated inflammation. These inflammatory responses seem essentially to be unmodified by bosentan, potentially representing new targets for therapy in this disorder.     

Factors Associated with Serum Brain Natriuretic Peptide Levels after the Fontan Procedure

Objective. Although a useful marker of heart failure in adults, the utility of brain natriuretic peptide concentration (BNP) for children after the Fontan procedure is not well studied. Design. BNP was measured in 510 patients who were 6–18 years old in the Pediatric Heart Network Fontan cross‐sectional study at a median of 8.2 years after Fontan. Patients underwent echocardiography, exercise testing, magnetic resonance imaging (MRI) and functional health status questionnaires. Associations of BNP with baseline patient characteristics, medical history and cross‐sectional assessment were examined with multivariable linear regression analyses. Results. The distribution of BNP was highly skewed, median 13.0 pg/mL (interquartile range: 7.1, 25.9), and was normalized with logarithmic transformation (logBNP). Among medical history variables, logBNP was greater in females (P= .02) and older patients (P < .001). Presence of pre‐Fontan systolic ventricular dysfunction, greater number of post‐Fontan complications, and thrombosis after Fontan were independently associated with higher logBNP (R²= 0.16). Age‐adjusted logBNP was significantly related to Fontan connection type (lower with extracardiac conduits, higher with atriopulmonary connection; P < .001). Lower physical functioning health status (R²= 0.05), lower chronotropic index during exercise (R²= 0.17), indices of diastolic dysfunction measured by echocardiography (R²= 0.15), and higher total ventricular mass on MRI (R²= 0.33) were related to higher logBNP. Conclusions. Despite a markedly abnormal circulation, BNP was variable but within a normal range in the majority of Fontan patients in this large outpatient cohort. Higher BNP was associated with several markers of suboptimal outcome, although associations were weak. The routine use of BNP as an outpatient surveillance tool in asymptomatic Fontan patients is not warranted.     

Craniorachischisis and Heterotaxia with Heart Disease in Twins: Link or Change Nature?

Craniorachischisis is a rare neural tube defect in which both acrania and a complete schisis of the vertebral column are present. Heterotaxy results from failure to establish normal left–right asymmetry during embryonic development and is characterized by a variable group of congenital anomalies that include complex cardiac malformations and situs inversus or situs ambiguous. We report a diamniotic twin pregnancy with two malformed fetuses affected one by craniorachischisis and the other by heterotaxya with paired right-sided viscera, asplenia, and complex congenital heart disease. The occurrence of severe congenital anomalies in both members of the twin pair implies a strong influence of genetic factors. At present, the genetic basis determining the different phenotypes observed in our twins is unknown. Our case with the simultaneous presence of both midline and laterality defects in twins supports the hypothesis that the midline plays a critical role in establishing left–right asymmetry in the body and that a mutation in a gene responsible for both heterotaxy and midline defects may be strongly supposed.     

Exercise Testing Identifies Patients at Increased Risk for Morbidity and Mortality Following Fontan Surgery

Objective. The objective of this study was to examine the relationship between exercise test data and mortality in patients who have had the Fontan procedure. Design. The study was designed as a retrospective cohort study. Setting. The study was set in a tertiary care center. Patients. All study participants were Fontan patients ≥16 years old who had cardiopulmonary exercise tests at our institution between November 2002 and March 2010. The first exercise test with adequate effort during the study period was retained for analysis. We enrolled 146 patients at a median age of 21.5 years (16.0–51.6); 15.8 years (1.2–29.9) after Fontan surgery. Outcome Measures. The outcome measures were exercise test data (peak oxygen consumption, peak heart rate, etc.); mortality. Results. Peak oxygen consumption averaged 21.2 ± 6.2 mL/kg/min, 57.1 ± 14.1% predicted. Follow‐up data were collected 4.0 ± 2.0 years (range 0.3–7.7) after the exercise test. Sixteen patients (11%) died during follow‐up; their peak oxygen consumption (16.3 ± 4.0 mL/kg/min) was significantly less than the survivors' (21.8 ± 6.2 mL/kg/min; P < .0001). Recursive partitioning and Cox proportional hazards modeling revealed that the hazard for death for patients with a peak oxygen consumption of <16.6 mL/kg/min was 7.5 (95% confidence interval: 2.6, 21.6; P < .0002) times that of patients with a higher peak oxygen consumption. Similarly, the hazard ratio for patients with peak‐exercise heart rates of <122.5 bpm was 10.6 (3.0, 37.1; 0 < 0.0002). Data from exercise tests could also identify patients at increased risk for a combined morbidity/mortality end point. Conclusions. In adults with Fontan surgery, exercise test data can identify patients at increased risk of midterm morbidity and mortality.     

Interventional Therapy of Supravalvular Pulmonary Stenosis via a Mechanical Valve in the Pulmonary Position

There is an increasing number of patients with congenital heart disease and pathology of the right ventricular outflow tract in whom a mechanical pulmonary valve replacement is chosen for permanent palliation. Despite corrective surgery, some of these patients may have residual or secondary supravalvular pulmonary stenosis or peripheral pulmonary stenosis, which necessitate interventional therapy after valve replacement. There is a general understanding that interventional therapy via a mechanical valve in pulmonary position may induce mechanical valve dysfunction and should therefore be avoided. We report our experience in three patients with a St. Jude Medical mechanical valve in pulmonary position and supravalvular pulmonary stenosis or a peripheral pulmonary stenosis where we have safely performed standard interventions (i.e., balloon angioplasty and stent implantation) across the mechanical valve without any complications. Our specific technique using a long sheath as safety guard, which holds the mechanical valve open during the procedure but allows the positioning of all mechanical devices and catheters necessary for the procedures, is described. In all patients, the long‐term follow‐up of the valve function is excellent.