FISH for 22q11.2 deletion not cost-effective for infants with congenital heart disease with microarray.

The objective of this study is to evaluate the yield of genetic testing in infants with congenital heart disease, who undergo surgical intervention prior to one year of age, and develop a cost-effective strategy to screen infants with congenital heart disease for genetic conditions while providing standard of care. 409 charts of patients with congenital heart disease, who underwent surgical intervention prior to one year of age, were retrospectively reviewed for cytogenetic testing results. 278 patients underwent cytogenetic testing, and 89.6 % of these patients had more than one cytogenetic test completed. The most commonly encountered chromosomal anomaly within the sample was Down Syndrome (12.5 %), followed by 22q11.2 Deletion Syndrome (4.6 %). G-Banded Karyotypes were abnormal in 10.5 % of patients, fluorescence in situ hybridization (FISH) probe for 22q11.2 deletion was abnormal in 7.1 % of patients. SNP microarray testing showed the highest yield and was abnormal in 33 % of patients. Based on the data at our institution, a more directed approach of genetic screening with only microarray would have saved our institution approximately $101, 200 on the 103 patients who underwent genetic evaluation with microarray reviewed. Screening infants with congenital heart disease for 22q11.2 deletion with FISH resulted in a loss of approximately $32,000 per 100 patients at our institution. Institutions should develop microarray-based protocols for genetic screening in patients with congenital heart disease with the anticipation of adding lesion-specific single gene testing as single gene testing becomes routinely available.

Is additional pulsatile pulmonary blood flow beneficial to patients with bidirectional Glenn?

OBJECTIVE: To compare the results of bidirectional Glenn when performed with or without pulsatile pulmonary blood flow in a cohort of patients with a single ventricle. METHODS: Records of 212 patients undergoing staged single ventricle palliation during a 10-year period were retrospectively reviewed. Of those, 103 (33 in pulsatile group A and 70 in nonpulsatile group B) were selected. RESULTS: Demographics and pre- and intraoperative variables were comparable for both groups. There was no difference in oxygen saturations immediately after the bidirectional Glenn in the 2 groups. The duration and output of chest tube drainage, incidence of chylothorax, and total length of stay was higher in group A. There was no difference in the number of diuretics or oxygen requirement upon discharge between groups. Pre-Glenn measurements showed a mean McGoon ratio in group A of 1.5 (1.46-1.57) and in group B of 1.59 (1.53-1.7) (P = .11); however, there was a significant difference in the ratio between groups at pre-Fontan measurements: group A, 1.76 (1.73-1.79) and group B, 1.6 (1.53-1.66) (P < .05). At pre-Fontan measurements there was a significant difference in mean pulmonary artery pressure between group A (14 mm [12.8-15.2]) and group B (10 mm [9.7-11]) (P < .05) and a trend toward higher incidence of venovenous collaterals in group A. There was no perioperative or interstage mortality in either group. CONCLUSIONS: Pulsatile bidirectional Glenn is associated with better pulmonary artery growth, which might improve long-term outcomes after Fontan. However, it was associated with a higher postoperative complication rate.

Pulmonary arterial capacitance in children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease: relation to pulmonary vascular resistance, exercise capacity, and survival.

BACKGROUND: Pediatric pulmonary arterial hypertension (PAH), whether idiopathic PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor for mortality in adults with PAH. However, the relation of PAC to pulmonary vascular resistance (PVR), exercise endurance, and survival is poorly defined in children. METHODS: Catheterization and clinical data of children with PAH (mean pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary shunts, stents, collaterals, or pulmonary venous hypertension were excluded. Primary outcomes were 6-minute walk distance and freedom from death/lung transplant. RESULTS: Forty-seven patients were studied. Nineteen (43%) had iPAH, and 28 (57%) had aPAH (7.1 ± 6.2 vs 8.4 ± 5.5 years, P = .45). Patients with iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC (PACi), lower exercise tolerance, and lower freedom from death/lung transplant than patients with aPAH. Both higher PVRi (P < .0001) and lower PACi (P = .02) were associated with shorter 6-minute walk distance. A PACi <0.70 mL/mm Hg per square meter or >1.25 mL/mm Hg per square meter and a PVRi >13 Wood units × m(2) were associated with decreased freedom from death or lung transplant. The relationships between PVRi and PACi and survival were independent of each other and not confounded by etiologic group. CONCLUSIONS: Low PACi and high PVRi are independently associated with low 6-minute walk distance and survival in children with PAH. Therefore, both should be assessed for better prognostication and management in this high-risk population.

Ventriculocoronary artery connections with the hypoplastic left heart: a 4-year prospective study: incidence, echocardiographic and clinical features.

Ventriculocoronary connections (VCCs), also called sinusoids, occur with hypoplastic left heart (HLH). Previous reports are limited to case reports, pathologic series, and surgical series with limited detail, which may underestimate the incidence and overestimate the severity of VCCs in HLH. A study was conducted to determine the incidence VCCs in HLH, their effect on survival, and their echocardiographic and clinical features. The echocardiograms and medical records of 100 consecutive neonatal HLH cases were analyzed. All had an aortic and a mitral valve diameter and a left ventricular (LV) volume less than Z-3. For palliation, Norwood, Sano, or hybrid procedures were used, and if the patient was alive, subsequent bidirectional Glenn and extracardiac Fontan procedures were applied. Cases were classified as manifesting mitral and aortic atresia (MAAA), mitral and aortic stenosis (MSAS), or mitral stenosis and aortic atresia (MSAA). All other diagnoses or any case with additional cardiac anomalies were excluded from the study. Overall, VCCs were found in 15% of the cases. They occurred in 56% of the MSAA subtype cases and were not statistically associated with a high mortality rate. However, in one case, large and multiple VCCs definitely caused or contributed to early death. All VCCs had a transmyocardial course, a turbulent color-Doppler flow, and a dominant usually retrograde systolic coronary artery flow pattern. The VCCs were associated (p < 0.05) with MSAA, endocardial fibroelastosis, and ascending aortic size less than 2 mm. As shown by the findings, 15% of the HLH patients had MSAA with VCCs. Unless the VCCs were large or extensive, they did not contribute to mortality. Detailed echocardiographic analysis of VCCs in HLH was feasible. Recent reports emphasize more severe cases.

Drotrecogin alfa (activated) in an infant with gram-negative septic shock.

The authors observed the effect of drotrecogin alfa (activated) in a case of pediatric severe sepsis. A 4-month-old male infant with Serratia marcescens septic shock, multiple organ dysfunction syndrome (MODS), and consumptive coagulopathy was admitted. The safety and efficacy of drotrecogin alfa (activated) has not yet been established for patients younger than 18 years of age. This is the first published report of the use of drotrecogin alfa (activated) in an infant with severe sepsis. Within 6 hours of starting therapy, there was a significant improvement in hemodynamics, which was not maintained after the drotrecogin alfa (activated) infusion was temporarily discontinued. No significant bleeding complications occurred during the infusion. A brain MRI on day 22 after drotrecogin alfa (activated) infusion showed bilateral small occipital hemorrhages. Drotrecogin alfa (activated) in this infant was temporally related to significant improvement. It is unknown whether the MRI brain lesions are related to severe sepsis with disseminated intravascular coagulation or drotrecogin alfa (activated) infusion. The authors believe that drotrecogin alfa (activated) should be considered in select children with life-threatening severe sepsis.

Congenital methemoglobinemia: a rare cause of cyanosis in the newborn--a case report.

Cyanosis is a physical finding that can occur at any age but presents the greatest challenge when it occurs in the newborn. The cause is multiple, and it usually represents an ominous sign, especially when it occurs in association with neonatal sepsis, cyanotic congenital heart disease, and airway abnormalities. Cyanosis caused by abnormal forms of hemoglobin can also be life-threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal hemoglobin, such as hemoglobin M, is traditionally discovered by electrophoresis, so the newborn screen, which is mandatory in several states, is a useful tool for the diagnosis. Although acquired methemoglobinemia, caused by environmental oxidizing agents, is common, congenital deficiency of the innate reducing enzyme is so rare that only a few cases are documented in the medical literature around the world. We present a neonate with cyanosis as a result of congenital deficiency of the reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase enzyme. This infant was found to be blue at a routine newborn follow-up visit. Sepsis, structural congenital heart disease, prenatal administration, and ingestion of oxidant dyes were excluded as a cause of the cyanosis by history and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and hemoglobin electrophoresis made the diagnosis of hemoglobin M unlikely as the cause of the methemoglobinemia (Hb A 59.4%, A2 1.8%, and F 38.8%). Red blood cell enzyme activity and DNA analysis revealed a homozygous form of the cytochrome b5 reductase enzyme deficiency. He responded very well to daily methylene blue and ascorbic acid administration, and he has normal growth and developmental parameters, although he shows an exaggerated increase in his methemoglobin level with minor oxidant stress such as diarrhea.