Low rate of prenatal diagnosis among neonates with critical aortic stenosis: insight into the natural history in utero.

OBJECTIVES: To better understand the natural history and spectrum of fetal aortic stenosis (AS), we aimed to (1) determine the prenatal diagnosis rate of neonates with critical AS and a biventricular (BV) outcome, and (2) describe the findings at fetal echocardiography in patients diagnosed prenatally. METHODS: A multicenter, retrospective study was performed on neonates who presented with critical AS and who were discharged with a BV outcome from 2000 to 2013. The prenatal diagnosis rate was compared with that reported for hypoplastic left heart syndrome (HLHS). We reviewed fetal echocardiographic findings in patients who were diagnosed prenatally. RESULTS: In only 10 (8.5%) of 117 neonates with critical AS and a BV outcome was the diagnosis made prenatally, a rate significantly lower than that for HLHS in the contemporary era (82%; P < 0.0001). Of the 10 patients diagnosed prenatally, all had developed left ventricular dysfunction by a median gestational age of 33 (range, 28-35) weeks. When present, Doppler abnormalities such as retrograde flow in the aortic arch (n = 2), monophasic mitral inflow (n = 3) and left-to-right flow across the foramen ovale (n = 8) developed late in gestation (median 33 weeks). CONCLUSION: The prenatal diagnosis rate of critical AS and a BV outcome among neonates is very low, probably owing to a relatively normal four-chamber view in mid-gestation with development of significant obstruction in the third trimester. The natural history contrasts with that of severe mid-gestation AS with evolving HLHS and suggests that the gestational timing of development of significant AS has an important impact on subsequent left-heart growth in utero.

Delayed cortical development in fetuses with complex congenital heart disease.

Neurologic impairment is a major complication of complex congenital heart disease (CHD). A growing body of evidence suggests that neurologic dysfunction may be present in a significant proportion of this high-risk population in the early newborn period prior to surgical interventions. We recently provided the first evidence that brain growth impairment in fetuses with complex CHD has its origins in utero. Here, we extend these observations by characterizing global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a progressive third trimester fall-off in cortical gray and white matter volumes (P < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS. Significant delays in cortical gyrification were also evident in HLHS fetuses (P < 0.001). In the HLHS fetus, local cortical folding delays were detected as early as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions and appear to precede volumetric brain growth disturbances, which may be an early marker of elevated risk for third trimester brain growth failure.

Left ventricular function and geometry in fetuses with severe tricuspid regurgitation.

OBJECTIVE: Neonatal congenital tricuspid valve (TV) dysplasia and/or displacement (Ebstein's malformation) with severe tricuspid regurgitation (TR) is a challenging condition in which outcomes are frequently poor. Little is known about left ventricular (LV) function during the perinatal period in patients with congenital TV disease. The objective of this study was to evaluate LV function in fetuses with congenital TV anomalies associated with significant TR. METHODS: Serial fetal echocardiograms in 16 fetuses with congenital TV dysplasia and/or displacement (five neonatal survivors and 11 fetal or neonatal deaths) were reviewed. LV stroke volume, LV end-diastolic volume (LVEDV), LV end-diastolic dimension (LVIDd), the LV eccentricity index, thoracic and cardiac areas and the cardiothoracic area ratio (CTAR), the right atrium area index, and LV longitudinal strains were compared according to gestational age and clinical outcome. RESULTS: The gestational age-adjusted LVEDV (Z-score) was lower in late gestation (-1.2 ± 1.2 at last examination ≥ 28 weeks) than earlier in gestation (0.3 ± 1.5 at last examination < 28 weeks) and LV output was lower than reported late-gestation normal values. LV short-axis dimension correlated with LV volume and CTAR. LV mid-septal strain was lower than the normal average of fetal mid-septal strain and correlated with the LV eccentricity index. Among these parameters, only the LV eccentricity index differed between survivors and non-survivors. CONCLUSION: LV function and anatomy are abnormal in fetuses with severe congenital TV anomalies and may be important contributors to outcome.

Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia.

OBJECTIVE: In patients with a left-sided congenital diaphragmatic hernia (CDH), the left ventricle (LV) is often compressed and smaller than normal. The objective of this study was to investigate whether small left heart dimensions prenatally normalize after birth in patients with CDH, or whether prenatal indices of left heart size and flow predict postnatal outcome. METHODS: Clinical and echocardiographic data were reviewed for patients diagnosed with left-sided CDH prenatally. Cardiac dimensions and flows were compared with normative data. Among liveborn patients, pre- and postnatal Z-scores of left heart structures were compared, and associations between prenatal indices and outcome were assessed. RESULTS: Of 125 patients diagnosed prenatally with CDH, 111 had a left-sided defect. Of these, 85 were liveborn, including 20 with congenital heart disease. Gestational age-adjusted dimensions of fetal left heart structures, including aortic valve diameter, mitral valve (MV) diameter, LV long-axis, LV short-axis and LV volume, were all smaller than normal (P < 0.001). On average, the LV contributed 33 +/- 8% of combined ventricular output, lower than the normal 40-50%. Z-scores of left heart structures increased from the prenatal echocardiogram to the postnatal study, with average changes ranging from 0.56 +/- 1.68 (aortic valve) to 1.39 +/- 1.85 (LV volume). Among liveborn patients, there was no association between prenatal left heart Z-scores and postnatal survival. CONCLUSIONS: Hypoplasia of and reduced flow through the left heart are common among fetuses with CDH. After birth and CDH repair, left heart dimensions generally normalize, with adequate size to support a biventricular circulation, even when there is very low flow through the left heart in mid- and late-gestation.

Clinical features of pulmonary arterial hypertension in young people with an ALK1 mutation and hereditary haemorrhagic telangiectasia.

BACKGROUND: Pulmonary arterial hypertension (PAH) has been linked to mutations in genes encoding two members of the transforming growth factor-beta family, BMPR2 and ALK1, the latter of which is also associated with hereditary haemorrhagic telangiectasia (HHT). Relatively little is known about the genetics of childhood PAH, or about the clinical features of PAH in young patients with an ALK1 mutation. METHODS AND RESULTS: Three individuals diagnosed with PAH at 4, 16 and 17 years of age were found on subsequent genetic screening to have non-synonymous mutations of ALK1. All probands met criteria for HHT, although two presented with PAH before HHT was diagnosed. Extended family history revealed relatives with HHT in all three kindreds, a presumptive family history of PAH in two, one with multiple family members dying from PAH at young ages. All three patients in this series had systemic or suprasystemic right ventricular pressure and significantly elevated pulmonary vascular resistance, initially not responsive to oxygen and/or inhaled nitric oxide. All patients had pulmonary arteriovenous malformations and systemic arterial desaturation. CONCLUSION: This report highlights ALK1 mutations associated with a variable PAH phenotype, including pulmonary arteriovenous malformations and severe PAH presenting early in life. Echocardiographic screening for elevated right ventricular pressure may be indicated in patients with HHT, particularly those with an identified ALK1 mutation. Clinical features or a family history of HHT should be elicited in children and adolescents with idiopathic PAH; ALK1 screening may be appropriate when such features are present.

A review of ductal stenting in hypoplastic left heart syndrome: bridge to transplantation and hybrid stage I palliation.

There is increasing interest in applying ductal stenting technology to high-risk patients with hypoplastic left heart syndrome (HLHS). In this review, we present the complete history and a comprehensive up-to-date analysis of all available data on the use of ductal stenting as part of various hybrid strategies for the combined medical and surgical management of HLHS.

Changes in left heart hemodynamics after technically successful in-utero aortic valvuloplasty.

OBJECTIVE: Severe aortic stenosis in the mid-gestation fetus can progress to hypoplastic left heart syndrome (HLHS). @ In-utero aortic valvuloplasty is an innovative therapy to promote left ventricular growth and function and potentially to prevent HLHS. This study evaluated the effects of mid-gestation fetal balloon aortic valvuloplasty on subsequent fetal left ventricular function and left heart Doppler characteristics. METHODS: We reviewed fetuses with aortic stenosis that underwent attempted in-utero aortic valvuloplasty between 2000 and 2006. Pre-intervention and the latest post-intervention fetal echocardiograms were analyzed to characterize changes in left heart function and Doppler characteristics in utero. RESULTS: Forty-two fetuses underwent attempted aortic valvuloplasty during the study period, 12 of which were excluded from analysis secondary to inadequate follow-up data, termination or fetal demise. Study fetuses (n = 30) underwent pre-intervention echocardiography at a median gestational age of 23 weeks, and were followed for a median of 66 +/- 23 days post-intervention. In 26 fetuses, aortic valvuloplasty was technically successful. Among these 26, left heart physiology was abnormal pre-intervention and improved or normalized after intervention in most cases: biphasic mitral inflow was present in 5/25 (20%) cases pre-intervention and in 21/23 (91%) post-intervention (P < 0.001); moderate or severe mitral regurgitation was present in 14/26 (54%) cases pre-intervention and in 5/23 (22%) post-intervention (P = 0.02); bidirectional flow across the patent foramen ovale was present in 0/26 cases pre-intervention and in 6/25 (24%) post-intervention (P = 0.01); antegrade flow in the transverse arch was present in 0/25 cases pre-intervention and in 17/26 (65%) post-intervention (P < 0.001). The left ventricular ejection fraction increased from 19 +/- 10% pre-intervention to 39 +/- 14% post-intervention (P < 0.001). These changes were not observed in control fetuses (n = 18). CONCLUSION: Fetal aortic valvuloplasty, when technically successful, improves left ventricular systolic function and left heart Doppler characteristics.

Chromosome 22q11 deletion in patients with truncus arteriosus.

The association between truncus arteriosus and chromosome 22q11 deletion is well recognized, but the frequency of a chromosome 22q11 deletion has not been characterized in a large series of patients with truncus arteriosus, and little is known about cardiovascular morphologic features associated with a chromosome 22q11 deletion in this group of patients. We prospectively enrolled 50 consecutive patients with truncus arteriosus who were admitted to The Children's Hospital of Philadelphia between November 1991 and December 2001. Patients were studied for chromosome 22q11 deletion using fluorescence in situ hybridization. Correlations between anatomic features and chromosome 22q11 deletion were assessed. A chromosome 22q11 deletion was detected in 20 of the 50 patients (40%). Anatomic features that were significantly associated with a chromosome 22q11 deletion included a right-sided aortic arch, an abnormal aortic arch branching pattern, both abnormal sidedness and branching of the aortic arch, and the combined category of either abnormal sidedness or branching of the aortic arch. There was a trend toward the association of discontinuous pulmonary arteries with a chromosome 22q11 deletion. Interruption of the aortic arch and truncal valve morphology and function did not correlate significantly with the presence of a chromosome 22q11 deletion. In conclusion, a chromosome 22q11 deletion is common in patients with truncus arteriosus, and those with abnormal sidedness and/or branching of the aortic arch are significantly more likely to have a deletion. Clinically important anatomic variables, such as abnormalities of the truncal valve and interrupted aortic arch, were not associated with a chromosome 22q11 deletion in this series.

Sarcoma of the mitral valve causing coronary arterial occlusion in children.

Primary tumors of the cardiac valves are rare. One of the most common reasons that left-sided cardiac tumors come to clinical attention is embolization to the systemic circulation. We present two children who suffered left coronary arterial occlusion due to embolization of a sarcoma of the mitral valve. A 6-year-old female who had been admitted to the hospital after cerebrovascular embolization of a fragment of sarcoma of the mitral valve experienced sudden cardiovascular collapse due to occlusion of the left coronary artery. She was placed on extracorporeal membrane oxygenation, and underwent coronary embolectomy and resection of the tumor from the mitral valve and its tendinous cords. Left ventricular function did not improve, and she underwent orthotopic heart transplantation. On follow-up 32 months after transplant, the patient is well, with no evidence of recurrence of or metastasis from the tumor. The tumor arose from the leaflets and tendinous cords of the mitral valve, and was composed grossly of multiple white nodules. Histopathologic evaluation disclosed fragments composed predominantly of peripheral spindle cells in an extensive fibromyxoid stroma. The mildly pleomorphic cells of the tumor gradually blended with adjacent pieces of the mitral valvar leaflet and tendinous cords. Immunohistochemical studies revealed strong staining for vimentin, smooth muscle actin, muscle specific actin, and myoglobin, suggesting myogenic differentiation. The other patient was a 2 1/2-year-old female who died suddenly at home. Grossly and histologically, the tumor was essentially identical to the first case, and there was a 3 cm string-like extension passing into the orifice of the left coronary artery. To put the cases in context, we compare them with other descriptions of this rare type of tumor.

Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age.

OBJECTIVE: Cardiovascular anomalies are present in 75% to 80% of patients with a chromosome 22q11 deletion. In the majority of cases, the cardiovascular defect becomes evident in the neonatal period and is often the initial manifestation of the chromosome 22q11 deletion syndrome. However, a 22q11 deletion may also be associated with cardiovascular defects that are less obvious, such as a vascular ring, which may not be diagnosed until the patient is older. The objective of this study was to determine the frequency and types of cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age. METHODS: We studied 29 patients diagnosed with a chromosome 22q11 deletion at a median age of 6.2 years (9 months to 45 years) who were subsequently referred for cardiovascular evaluation. Comprehensive cardiologic evaluation was performed, with transthoracic echocardiography (N = 28) and/or magnetic resonance imaging (N = 6), including imaging of the aortic arch. The frequency of cardiovascular anomalies diagnosed in these patients and the need for intervention were assessed. RESULTS: Cardiovascular anomalies were detected in 11 (38%) patients: 3 with a vascular ring formed by a right aortic arch with an aberrant left subclavian artery and left-sided ligamentum arteriosum, 3 with a right aortic arch with mirror-image branching of the brachiocephalic arteries (no vascular ring; 1 with a patent ductus arteriosus), 4 with a left aortic arch with an aberrant right subclavian artery (no vascular ring; 1 with a patent ductus), and 1 with a left superior vena cava draining to the coronary sinus. The median age at diagnosis in these 11 patients was 3 years (9 months to 28 years). The remaining 18 patients had normal cardiovascular anatomy. All 3 patients with vascular rings subsequently underwent surgical repair, and 1 patient with a ductus arteriosus underwent transcatheter coil occlusion. CONCLUSIONS: The frequency of cardiovascular anomalies necessitating intervention in patients referred for cardiovascular evaluation after diagnosis of a chromosome 22q11 deletion beyond 6 months of age is 14% in our experience. Routine screening for cardiovascular anomalies, including echocardiography and other imaging studies to identify the laterality and branching pattern of the aortic arch, is indicated in patients diagnosed with 22q11 deletion beyond 6 months of age and is particularly critical for patients with respiratory or feeding disorders.

Hemidiaphragmatic paralysis increases postoperative morbidity after a modified Fontan operation.

OBJECTIVES: After a Fontan procedure, forward pulmonary blood flow is augmented during inspiration because of negative intrathoracic pressure. Total pulmonary blood flow is higher during inspiration. With hemidiaphragmatic paralysis, inspiratory augmentation of pulmonary flow is lost or diminished. The objective of this study was to compare early postoperative morbidity after the modified Fontan operation in patients with and without hemidiaphragmatic paralysis. METHODS: A case-control analysis was performed comparing 10 patients with documented hemidiaphragmatic paralysis against 30 patients without paralysis who were matched for diagnosis, fenestration, and age. The following early postoperative outcomes were assessed: duration of ventilator support, duration of hospital stay, incidence of ascites, prolonged effusions, and readmission. RESULTS: Preoperatively, there were no significant differences between the 2 groups. However, among the postoperative outcomes, the duration of hospital stay (25.4 +/- 16.6 days vs 10.8 +/- 6.3 days; P =.03), incidence of ascites (70% vs 3%; P <.001), prolonged pleural effusions (60% vs 13%; P =.007), and readmission (50% vs 7%; P =.007) were significantly greater in patients with hemidiaphragmatic paralysis than in those without hemidiaphragmatic paralysis. CONCLUSIONS: Hemidiaphragmatic paralysis after the modified Fontan operation is associated with an increase in early morbidity. Care should be taken to avoid injury to the phrenic nerve. Patients with prolonged effusions should be evaluated for hemidiaphragmatic paralysis.

Recurrent arch obstruction after repair of isolated coarctation of the aorta in neonates and young infants: is low weight a risk factor?

BACKGROUND: Repair of aortic coarctation is often delayed in small infants because of the belief that such patients are at risk of recurrent arch obstruction and that growth will decrease this risk. To determine whether low weight was a risk factor for recurrent arch obstruction, we reviewed our experience with coarctation repair via left thoracotomy in infants less than 3 months of age. METHODS: From 1990 to 1999, 103 patients less than 3 months of age underwent repair of aortic coarctation through a left thoracotomy. Median age was 18 days (1-90 days), with 45 patients less than 2 weeks. Median weight was 3.3 kg (1.0-6.4 kg) and 14 patients were less than 2 kg. The method of repair was resection and end-to-end anastomosis in 64 patients, subclavian flap angioplasty in 34, and patch augmentation of the arch in 5. Demographic, echocardiographic, and operative variables were analyzed for correlation with recurrent arch obstruction. RESULTS: One early and 1 late death occurred, both in patients who had complications but no evidence of recoarctation. At median follow-up of 24 months, reinterventions for recurrent arch obstruction were performed in 15 patients. The median time to reintervention was 5 months and was less than 1 year in 12 patients. Kaplan-Meier freedom from arch reintervention was 88% at 1 year (95% confidence intervals: 82%-94%) and 82% at 5 years (95% confidence intervals: 72%-92%). Factors associated with shorter duration to arch reintervention by univariable Cox regression included younger age (continuous, P =.01; <2 weeks, P =.005), smaller transverse arch (absolute diameter, P <.001; indexed to weight, P =.03; indexed to ascending aortic diameter, P =.02), and smaller ascending aorta (absolute diameter, P =.02). Smaller absolute transverse arch diameter and younger age were the only independent predictors of shorter time to arch reintervention by multivariable Cox regression analysis. Weight and type of repair did not correlate with risk of recoarctation. CONCLUSIONS: Low weight is not a risk factor for recurrent obstruction after repair of coarctation of the aorta in infants less than 3 months of age. Rather, risk of recoarctation is more a function of the anatomy of the arch. Thus, it is not indicated to delay repair in low weight infants with the goal of achieving growth.

A prospective randomized study comparing volume-standardized modified and conventional ultrafiltration in pediatric cardiac surgery.

BACKGROUND: Modified ultrafiltration has been touted as superior to conventional ultrafiltration for attenuating the consequences of hemodilution after cardiac surgery with cardiopulmonary bypass in children. We conducted a prospective randomized study to test the hypothesis that modified and conventional ultrafiltration have similar clinical effects when a standardized volume of fluid is removed. METHODS: From October 1998 to September 1999, 110 children weighing 15 kg or less (median weight 6.1 kg, median age 6.3 months) undergoing surgery with cardiopulmonary bypass for functionally biventricular congenital heart disease were randomized to conventional (n = 67) or arteriovenous modified ultrafiltration (n = 43) for hemoconcentration. The volume of fluid removed with both methods was standardized as a percentage of effective fluid balance (the sum of prime volume and volume added during cardiopulmonary bypass minus urine output): in patients weighing less than 10 kg, 50% of effective fluid balance was removed, whereas 60% was removed in patients weighing 10 to 15 kg. Hematocrit, hemodynamics, ventricular function, transfusion of blood products, and postoperative resource use were compared between groups. RESULTS: There were no significant differences between groups in age, weight, or duration of cardiopulmonary bypass. The total volume of fluid added in the prime and during bypass was greater in patients undergoing conventional ultrafiltration than in those receiving modified ultrafiltration (205 +/- 123 vs 162 +/- 74 mL/kg; P =.05), although the difference was due primarily to a greater indexed priming volume in patients having conventional ultrafiltration. There was no difference in the percentage of effective fluid balance that was removed in the 2 groups. Accordingly, the volume of ultrafiltrate was greater in patients receiving conventional than modified ultrafiltration (95 +/- 63 vs 68 +/- 28 mL/kg; P =.01). Preoperative and postoperative hematocrit levels were 35.6% +/- 6.6% and 36.3% +/- 5.6% in patients having conventional ultrafiltration and 34.4% +/- 6.7% and 38.7% +/- 7.5% in those having modified ultrafiltration. By repeated-measures analysis of variance, patients receiving modified and conventional ultrafiltration did not differ with respect to hematocrit value (P =.87), mean arterial pressure (P =.85), heart rate (P =.43), or left ventricular shortening fraction (P =.21) from baseline to the postbypass measurements. There were no differences between groups in duration of mechanical ventilation, stay in the intensive care unit, or hospitalization. CONCLUSIONS: When a standardized volume of fluid is removed, hematocrit, hemodynamics, ventricular function, requirement for blood products, and postoperative resource use do not differ between pediatric patients receiving conventional and modified ultrafiltration for hemoconcentration after cardiac surgery.

Neonatal repair of truncus arteriosus: continuing improvement in outcomes.

BACKGROUND: Repair of truncus arteriosus in the neonatal and early infant periods has become standard practice at many centers. We reviewed our recent experience with repair of truncus arteriosus in neonates, with a focus on early and intermediate outcomes. METHODS: From July 1992 to December 1999, 65 patients 1 month of age or less underwent primary complete repair of truncus arteriosus. Median age was 10 days, and median weight was 3.2 kg. Major associated anomalies included moderate or severe truncal valve regurgitation in 15 patients (23%), interrupted aortic arch in 8 (12%), coronary artery abnormalities in 12 (18%), and nonconfluence of the pulmonary arteries in 3 (5%). Median durations of cardiopulmonary bypass and cardioplegic arrest were 172 minutes and 90 minutes, respectively. Circulatory arrest was employed only in 7 patients undergoing concomitant repair of interrupted arch. Reconstruction of the right ventricular outflow tract was achieved with an aortic (n = 39) or pulmonary (n = 26) allograft valved conduit (median diameter, 12 mm). Replacement (n = 6) or repair (n = 5) of a regurgitant truncal valve was performed in 11 patients, and interrupted arch was repaired in 8. RESULTS: There were three early deaths (5%). Early reoperations included reexploration for bleeding in 3 patients, emergent replacement of a pulmonary outflow conduit that failed acutely in 1 patient, and placement of a permanent pacemaker in 1. Mechanical circulatory support was required in 1 patient. During the median follow-up of 32 months, there were two deaths. The Kaplan-Meier estimate of survival was 92% at 1 year and beyond. The only demographic, diagnostic, or operative factors significantly associated with poorer survival over time were operative weight of 2.5 kg or less (p = 0.01) and truncal valve replacement (p = 0.009). Actuarial freedom from conduit replacement among early survivors was 57% at 3 years. CONCLUSIONS: Repair of truncus arteriosus in the neonatal period can be performed routinely with excellent survival, even in patients with major associated abnormalities.

Patterns of right aortic arch and mirror-image branching of the brachiocephalic vessels without associated anomalies.

It is unusual to have a right aortic arch with mirror-image branching of the brachiocephalic vessels and no associated congenital cardiac anomalies. Pathogenetic factors of this anomaly, and associated development of the derivatives of the pharyngeal arches, have not been explored extensively. Eleven patients with a mirror-image right aortic arch and no intracardiac anomalies have undergone evaluation at our institution since 1987. Of these, 4 had stenosis (n = 2) or atresia (n = 2) of the proximal left pulmonary artery. These included 2 with bilateral ductus arteriosus. Six patients had a vascular ring formed by a ductus arteriosus or ligamentum arteriosum from the descending aorta to the left pulmonary artery. Six patients were evaluated for deletion within the DiGeorge critical region of chromosome 22q11. All 6 of the patients with a vascular ring underwent division of the ductus arteriosus or ligamentum through a left lateral thoracotomy. None of the patients with stenosis or atresia of the LPA have undergone intervention. Two of the 6 patients who underwent evaluation for chromosome 22q11 deletion were found to have the deletion. At a median follow-up of 7 years (15 months to 12 years), the patients who underwent division of the ring are all alive and asymptomatic. Two of these patients have undergone repeat magnetic resonance imaging, 1 of whom had mild residual tracheal compression. A right aortic arch with mirror-image branching of the brachiocephalic vessels and no associated intracardiac anomalies is extremely uncommon. We have observed two basic patterns of this lesion: (1) with associated abnormalities of the proximal left pulmonary artery, (2) with a vascular ring formed by a ductus arteriosus or ligamentum from the descending aorta to the left pulmonary artery. Pathogenetic considerations are explored, with a focus on flow-related vascular development and the role of deletions within chromosome 22q11.

Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching.

OBJECTIVES: The purpose of this study was to determine the frequency of chromosome 22q11 deletions in patients with isolated anomalies of the aortic arch and its branches. BACKGROUND: Chromosome 22q11 deletions are often present in patients with certain forms of congenital cardiovascular disease, including tetralogy of Fallot, truncus arteriosus and interruption of the aortic arch. Among patients with these anomalies, chromosome 22q11 deletion is more common in those with abnormal aortic arch laterality or branching. METHODS: We studied 66 patients with isolated anomalies of the aortic arch and no associated intracardiac defects for deletions within chromosome 22q11, using fluorescence in situ hybridization with the cosmid probe N25 (D22S75). Arch anomalies included: double aortic arch (n = 22); right aortic arch with aberrant left subclavian artery (n = 28); right aortic arch with mirror-image branching and a vascular ring formed by a left-sided ductus from the descending aorta (n = 5); right aortic arch with mirror-image branching and no vascular ring (n = 4); and left aortic arch with aberrant right subclavian artery (n = 7). In addition, four patients had a cervical aortic arch, four had aortic coarctation and six had hypoplasia/atresia of the proximal pulmonary arteries. RESULTS: Chromosome 22q11 deletions were found in 16 patients (24%) across the full spectrum of anomalies studied. Among the morphologic variables analyzed, only hypoplasia/atresia of the proximal pulmonary arteries correlated with the deletion (p = 0.03). Among patients with a double arch, the frequency of chromosome 22q11 deletion was higher in those with an atretic minor arch than it was in those with a patent minor arch (p = 0.02). CONCLUSIONS: Chromosome 22q11 deletion is associated with isolated anomalies of laterality or branching of the aortic arch in 24% of cases in our series. These findings should alert the clinician to consider deletion screening in patients with isolated anomalies of the aortic arch.

Outcomes of neonates with congenital heart disease.

One of the most important advances of the past 10 to 15 years in the field of pediatric cardiology is the improvement in prognosis for neonates with complex congenital heart disease. During the past 18 months, several publications have addressed outcomes in neonates with congenital heart disease. Many of these reports demonstrate continuing improvement in preoperative, early postoperative, and late postoperative survival among patients with complex neonatal heart defects. Other reports shed substantial new light on late functional outcome, especially neurodevelopmental status. In addition to data on survival, morbidity, and functional status, we discuss developments in perioperative evaluation and management that are likely to further the trend toward improved outcome for neonates with complex congenital heart disease.

Perioperative administration of angiotensin converting enzyme inhibitors decreases the severity and duration of pleural effusions following bidirectional cavopulmonary anastomosis.

BACKGROUND: Pleural effusions after bidirectional cavopulmonary anastomosis remain a significant cause of morbidity. Prolonged effusions in such patients have been associated with persistent elevations in plasma renin and angiotensin II. METHODS: We conducted a controlled study in 36 patients (median age 8 months) undergoing bidirectional cavopulmonary anastomosis. Enalapril (5 mcg/kg) was administered intravenously within 1 hour of surgery and every 12 hours thereafter in 18 patients; when these patients were tolerating feeds, enalapril was switched to enteral captopril (3 mg/kg/day) every 8 hours. The other 18 patients did not receive perioperative angiotensin converting enzyme inhibitors. Using standardized criteria for discontinuation of chest tubes (< 2 mL/kg/day), volume and duration of pleural drainage were compared between groups. RESULTS. There were no differences between groups in demographic, diagnostic, or hemodynamic factors. There was no difference in cardiopulmonary bypass time between groups and no difference in postoperative pulmonary arterial pressures. The duration of pleural drainage was shorter (2.2+/-1.4 vs 5.9+/-1.4 days, p<0.001) and the volume less during the first 24 hours (4.7+/-1.2 vs 7.7+/-2.1 mL/kg, p<0.001) and overall (10.6+/-2.4 vs 19.6+/-4.5 mL/kg, p<0.001) in patients who received angiotensin converting enzyme inhibitors than those who did not. Readmission for persistent effusions was required in 3 patients who did not receive angiotensin converting enzyme inhibitors and none who did (p=0.11). CONCLUSIONS: Perioperative administration of angiotensin converting enzyme inhibitors is associated with decreased severity and duration of pleural effusions following bidirectional cavopulmonary anastomosis.

Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is frequently diagnosed prenatally, but this has not been shown to improve surgical outcome. METHODS AND RESULTS: We reviewed patients with HLHS between July 1992 and March 1999 to determine the influence of prenatal diagnosis on preoperative clinical status, outcomes of stage 1 surgery, and parental decisions regarding care. Of 88 patients, 33 were diagnosed prenatally and 55 after birth. Of 33 prenatally diagnosed patients, 22 were live-born, and pregnancy was terminated in 11. Of 22 prenatally diagnosed patients who were live-born, 14 underwent surgery, and parents elected to forego treatment in 8. Of 55 patients diagnosed postnatally, 38 underwent surgery, and 17 did not because of parental decisions or clinical considerations. Prenatally diagnosed patients were less likely to undergo surgery than patients diagnosed after birth (P:=0.008). Among live-born infants, there was a similar rate of nonintervention. Among patients who underwent surgery, survival was 75% (39/52). All patients who had a prenatal diagnosis and underwent surgery survived, whereas only 25 of 38 postnatally diagnosed patients survived (P:=0.009). Patients diagnosed prenatally had a lower incidence of preoperative acidosis (P:=0.02), tricuspid regurgitation (P:=0.001), and ventricular dysfunction (P:=0.004). They were also less likely to need preoperative inotropic medications or bicarbonate (P:=0.005). Preoperative factors correlating with early mortality included postnatal diagnosis (P:=0.009), more severe acidosis (P:=0.03), need for bicarbonate or inotropes (P:=0.008 and 0.04), and ventricular dysfunction (P:=0.05). CONCLUSIONS: Prenatal diagnosis of HLHS was associated with improved preoperative clinical status and with improved survival after first-stage palliation in comparison with patients diagnosed after birth.