Magnetic resonance imaging in the diagnosis and follow up of Takayasu's arteritis in children.

BACKGROUND: Takayasu's arteritis (TA) has a mortality rate of up to 40% in children. Because the clinical presentation of TA is often non-specific, accurate and prompt diagnosis depends on a high degree of awareness and appropriate laboratory and imaging studies. OBJECTIVE: To examine the use of advanced magnetic resonance imaging (MRI) in evaluating, gauging activity, and following the complications of TA. METHODS AND RESULTS: T1 weighted, T2 weighted, contrast enhanced MR images, and MR angiograms of the chest and abdomen were obtained in three children (age range 11-14 years). The MRI studies confirmed the diagnosis of active TA and were repeated to evaluate response to treatment. Two patients showed complete resolution of lesions found on MRI at six and 12 months' follow up, while the third patient showed no significant improvement. CONCLUSION: MRI can be used to help establish the initial diagnosis of TA in children, and it can also be used to monitor disease activity and to guide treatment.

Alveolar capillary dysplasia: diagnostic potential for cardiac catheterization.

OBJECTIVE: Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. Infants with this condition die despite maximal medical intervention including inhaled nitric oxide therapy and extracorporeal membrane oxygenation. To date, diagnosis of this lethal condition was made by open lung biopsy or during postmortem examination. We examined the possibility that distinct cardiac catheterization findings could be used in the diagnosis of this lethal disorder. STUDY DESIGN: We present three infants with fatal persistent pulmonary hypertension of the newborn refractory to extracorporeal membrane oxygenation and inhaled nitric oxide therapy, two with postmortem autopsy confirmation of alveolar capillary dysplasia. Each infant underwent cardiac catheterization to complete the diagnostic evaluations. RESULTS: Significant right ventricular hypertension and normal pulmonary venous return were demonstrated, but a markedly diminished or absent capillary blush phase was noted in each infant. This finding is distinct from the normal capillary blush seen in infants with persistent pulmonary hypertension of the newborn of other etiologies. CONCLUSION: Cardiac catheterization may provide a useful alternative to tissue examination in the diagnosis of alveolar capillary dysplasia.

Pediatric cardiac transplantation. The Stanford experience.

BACKGROUND: Cardiac transplantation for children with endstage heart disease has become an accepted form of therapy and is being practiced with increasing frequency and improving short-term outcome. METHODS AND RESULTS: To assess the medium-term outcome of pediatric cardiac transplantation, we analyzed our experience with 72 patients under the age of 18 (range, 0.1 to 17.7 years; mean, 9 +/- 6.4 [SD]) who underwent orthotopic cardiac transplantation at Stanford University between 1977 and 1993. There were 38 male and 34 female patients. Preoperative diagnoses included congenital heart disease in 24 (33%), idiopathic cardiomyopathy in 27 (37%), viral cardiomyopathy in 12 (17%), and familial cardiomyopathy in 7 (10%) patients. Immunosuppressive management has evolved over time and has included a tapering schedule of steroids, azathioprine, rabbit antithymocyte globulin, cyclosporine in all patients after 1980, and induction with OKT3 since 1987. Operative mortality rate was 12.5 +/- 4.0% (mean +/- 70% confidence intervals). Actuarial survival estimates at 1, 5, and 10 years are 75 +/- 7.1%, 60 +/- 6.4%, and 50 +/- 8.1% (mean +/- 1 SEM), respectively. Causes of death included infection in 8 (28% of deaths), rejection in 7 (24%), graft coronary disease in 5 (17%), pulmonary hypertension in 4 (14%), and nonspecific graft failure in 2 (7%) patients. Survival rates were similar for patients over and those under age 10 years (including the infant cohort of 18 patients transplanted since 1986). Currently, there are 43 patients alive, all in New York Heart Association functional class I. Only 22 +/- 5.6% of patients were free of rejection at 1 year, but 86 +/- 5.4% were free of rejection-related death at 10 years. At 1 year, only 37 +/- 6% of patients were free from any infection, but 88 +/- 4.2% remained free of infection-related death at 5 years. Actuarial freedom from graft coronary artery disease (angiographic or autopsy proven) was 85 +/- 6.6% at 5 years and from coronary artery disease-related death was 91 +/- 4.7%. CONCLUSIONS: These data demonstrate satisfactory medium-term outcome of cardiac transplantation in selected pediatric patients with end-stage heart disease, but further progress is necessary to more effectively control rejection, infection, and graft coronary disease.

Cardiovascular evaluation in Turner syndrome: utility of MR imaging.

Forty patients with karyotypically proven Turner syndrome were prospectively studied using magnetic resonance imaging (MRI) and echocardiography in order to determine the frequency of cardiovascular anomalies and to assess the utility of both imaging modalities as methods for cardiovascular evaluation in Turner syndrome. Cardiovascular anomalies were found in 45% of patients. A high absolute prevalence of bicuspid aortic valve (17.5%) and aortic coarctation (12.5%) were observed relative to comparable series. Of clinically significant abnormalities, three of five aortic coarctations and four of five ascending aortic dilatations were solely MRI detected and not evident at echocardiographic examination. MRI is thus seen as a valuable adjunct to echocardiography in the cardiovascular evaluation of Turner syndrome patients. The usefulness of MRI primarily relates to its ability to provide excellent visualisation of the entire thoracic aorta where a large proportion of clinically significant anomalies occur in Turner syndrome.

Current approach to hypoplastic left heart syndrome. Palliation, transplantation, or both?

Over the past 3 years, 35 newborn infants have been referred for surgical management of hypoplastic left heart syndrome. Surgical palliation (first-stage Norwood) or cardiac transplantation was offered. Twenty-four families (68%) chose palliation and 11 families (32%) chose cardiac transplantation. Of the 11 infants listed for cardiac transplantation, five underwent transplantation. Because of a lack of donors after an average wait of 25 days (19 to 31), the remaining six infants underwent palliation, with no perioperative deaths. Of the 30 infants undergoing palliation, including crossovers, 20 (67%) survived the first operative stage. Among the last 19 infants undergoing palliation in 1990, the early survival was 84%. Risk factors determined for poor outcome were year of operation (p less than 0.001) and circulatory arrest time greater than 50 minutes (p less than 0.001). Among the 13 infants undergoing palliation with a circulatory arrest time of less than 50 minutes, there were 12 survivors (92%); among 12 having a circulatory arrest time of more than 50 minutes, there were four survivors (33%). At intermediate follow-up, six infants have undergone second-stage procedures (Glenn), with five survivors. There were eight late deaths, four caused by respiratory infections and four caused by cardiac problems, including a thrombosed shunt in one infant. Three of five infants are alive and doing well after cardiac transplantation. Size of aorta, tricuspid regurgitation, and ventricular wall thickness did not prove to be risk factors. Given the existing data, we believe these infants should be managed selectively on the basis of donor availability and family wishes.

Ebstein's anomaly appearing in the neonate. A new surgical approach.

Ebstein's anomaly appearing during the neonatal period carries a high mortality rate. These infants exhibit cyanosis, acidosis, and congestive heart failure. The pathophysiologic characteristics consist of severe tricuspid regurgitation and functional pulmonary atresia. As a result of the inability of the right ventricle to generate forward flow through the pulmonary arteries, these infants remain dependent on ductal patency. Since May 1988, five newborn infants with severe Ebstein's anomaly have been admitted for treatment at our institution. At initial examination, they weighed 3.6 +/- 1.8 kg and had a mean oxygen tension of 29.6 +/- 2.3 mm Hg and a mean pH of 7.20 +/- 0.05. Chest roentgenography demonstrated a mean cardiothoracic ratio of 0.81 +/- 0.02. As determined by echocardiography, the right atria were massively enlarged, severe tricuspid regurgitation was present in all patients, and the pulmonary valves were not opening. All infants were dependent on prostaglandin E1 and attempts to wean them from this drug were unsuccessful. Palliative treatment consisted of tricuspid closure with autologous pericardium and an aortopulmonary shunt of 4 mm polytetrafluoroethylene tubing. There were no operative or late deaths. At discharge, mean oxygen tension was 42.2 +/- 0.85 mm Hg and mean systemic oxygen saturation was 83.2% +/- 1.94%. Infants have grown satisfactorily during the follow-up period. Three infants have since returned for further surgical intervention. One infant, at 11 months of age, underwent a Glenn anastomosis for progressive oxygen desaturation. Two infants have returned, at ages 23 and 22 months, for Fontan procedures, which represent their definitive operative management. We believe this new procedure offers excellent palliative treatment for Ebstein's anomaly in critically ill neonates. Feasibility of later definitive correction is demonstrated by the good results obtained with the Fontan procedure in two infants.

Late pulmonary sequelae of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS: We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS: Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS: Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known.

Septal origin of sustained ventricular tachycardia in a patient with right ventricular outflow tract obstruction after correction of tetralogy of Fallot.

Right ventricular hypertension and ventricular arrhythmias are risk factors for sudden death after correction of tetralogy of Fallot, but sustained ventricular tachycardia has been reported only in patients without residual hemodynamic abnormalities. A patient with right ventricular hypertension and hypotensive ventricular tachycardia tolerated the arrhythmia better after relief of right ventricular outflow tract obstruction. This case provides insight into the relationship between hemodynamic abnormalities and the clinical consequences of arrhythmias. To our knowledge, it is the first report of ventricular tachycardia originating in scar adjacent to the ventricular septal defect patch after correction of tetralogy of Fallot.

Phrenic nerve injury complicating closed cardiovascular surgical procedures for congenital heart disease.

Phrenic nerve injury (PNI) with resulting hemidiaphragmatic paralysis occurred in 19 (2.1 +/- 0.5%) of 891 closed cardiac surgical procedures during a twenty-three-year period. Diagnosis was confirmed by standard radiographic criteria. Phrenic nerve injury was most commonly noted following systemic-pulmonary artery anastomosis, ligation of persistent ductus arteriosus plus pulmonary artery banding, and atrial septectomy. Most patients were managed conservatively (nasotracheal or orotracheal intubation and positive end-expiratory pressure). Although no deaths were a direct result of PNI, major complications occurred in 15 of the 19 instances of PNI (79% +/- 10%). The serious morbidity and the hospital costs associated with this complication, however, underscore the cardinal importance of prevention. If injury does occur, early surgical intervention (diaphragmatic plication) in very young infants may reduce the attendant morbidity, but the complete role of diaphragmatic plication remains to be defined.

Severe superior vena cava syndrome and hydrocephalus after the Mustard procedure: findings and a new surgical approach.

Some degree of obstruction of the superior vena cava is common after the Mustard operation for transposition of the great arteries. This can cause superior vena cava syndrome, which in extreme cases may lead to hydrocephalus in young children. While revision of the intra-atrial baffle can be performed, this procedure is associated with significant morbidity and mortality and may not resolve the problem. We describe an alternative operative approach in a group of patients who had superior vena cava syndrome after the Mustard procedure: anastomosis of the innominate vein to the left atrial appendage. This procedure is not complicated to perform and is safe; symptoms were relieved in all patients.

Cardiac localization of transvascular bioptome using 2-dimensional echocardiography.

Two-dimensional (2-D) echocardiography was added to standard fluoroscopic localization of transvascular endomyocardial biopsy in 7 children with heart muscle disease whose ages were 6 months to 18 years. One left ventricular and 11 right ventricular biopsies were carried ot without complications using the fluoroscopic-echocardiographic technique. Two-dimensional echocardiographic monitoring has the advantages of reducing radiation exposure and providing anatomic information about intracardiac structures as well as bioptome localization. Lateral beam spread and reverberation artifacts represent potential problems with 2-D echocardiography, but they did not cause significant difficulties in this study.

The durability of porcine xenograft valves and conduits in children.

One hundred four patients younger than 20 years of age underwent intracardiac xenograft valve replacement (n = 41) or extracardiac conduit implantation (n = 63). Long-term follow-up averaged 4.5 and 4.3 years, respectively, and cumulative follow-up totaled 344 patient-years (pt-yr). Thirty patients were followed more than 5 years. Functional results and survival were satisfactory, but valve failure and conduit failure prompted 23 reoperations at linearized rates of 10.1 +/- 2.6% and 4.1 +/- 1.5%/pt-yr, respectively. The rate of valve failure due to leaflet fibrocalcification (primary tissue failure [PTF] was 8.1 +/- 2.4%/pt-yr. Among patients who underwent valve replacement, 52 +/- 13% were free of reoperation at 5 years (59 +/- 13% for PTF only), as were 80 +/- 9% of patients who received an extracardiac conduit. There were no deaths associated with the 22 late reoperations or with the 21 reoperations for PTF. Valve failure was due to PTF in 80% of cases; conversely, isolated valvular PTF was the cause of conduit failure in only one of eight patients. The most common cause of conduit failure was exuberant pseudointimal proliferation in the proximal conduit, which was seen in six of eight patients (75%) with or without other sites of obstruction and responsible for nine of the 15 obstructions (60%). These results underscore the palliative nature of these procedures, militate against indiscriminant use of conduits, prompt consideration of alternative nonconduit techniques where possible, and reemphasize the clinical need for superior valve substitutes and biomaterials for use in the pediatric age group.

A double blind study of the effects of oral indomethacin in preterm infants with patent ductus arteriosus who failed medical management.

Over a two year period, 52 infants were found to have clinical signs of patent ductus arteriosus (PDA). Twenty-seven responded to fluid restriction and furosemide; the remaining 25 infants entered the Indomethacin (IN) study protocol. Their mean (+/- SE) gestational age was 29.3 (+/- 0.6) weeks and birth weight was 1,142 (+/- 80) gm. Either a placebo or IN (0.25 mg/kg) orally was given for two doses, 24 hours apart; if no response occurred, the patient was crossed over to the opposite medication. Using Chi-square analysis, a significant response rate to IN was found. There were no significant differences in birth weights, gestational ages, or fluid intake between responders and nonresponders. However, both responders and nonresponders required a prolonged ventilator course, suggesting factors other than PDA causing prolonged ventilatory requirements in these babies.

Renal responses of the fetal lamb to fetal or maternal volume expansion.

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.

Acute effects of maternal ethanol infusion on fetal cardiac performance.

In adult animals and man, both acute and chronic ethanol intake is associated with depression of myocardial performance. Accordingly, the cardiac effects of maternal ethanol infusions, in a manner comparable to common obstetric practice of inhibition of premature labor with ethano mighte for inhibition of premature labor, were evaluated in six chronically instrumented fetal sheep. Fetal and ewe arterial PO2, PCO2, and pH values remained within normal limits with infusion rates of 15 c.c. per kilogram of 10 per cent ethanol over two hours (blood ethanol = 110 mg. per cent) and 15 c.c. per kilogram over one hour (blood ethanol = 210 mg. per cent). Fetal instrument evaluation (for 14 to 30 days after operation) provided data concerning pressures and cardiac dimensions which allowed analysis of left ventricular performance. Ethanol produced a significant depression of the extent (p less than 0.01) and velocity (p less than 0.001) of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular circumferential fiber shortening (p less than 0.01). These indices of cardiac contractility were depressed in the absence of changes in end diastolic diameter, left atrial pressure, and systemic arterial pressure. Thus, the practice of inhibition of premature labor with ethano6 might contribute to depressed myocardial performance in the neonatal period.

Pharmacologic closure of patent ductus arteriosus in the premature infant.

The prostaglandins affect smooth-muscle tone of the ductus arteriosus. Patent ductus often complicates the clinical course of prematurely born infants with respiratory-distress syndrome. In the present study, a single oral or rectal dose of a potent inhibitor of prostaglandin synthesis, indomethacin, was administered to six consecutive premature infants with the syndrome who would otherwise have undergone surgical ligation of the patent ductus. Within 24 hours all the clinical symptoms and physical, echocardiographic and radiographic signs attributable to substantial left-to-right shunting through a patent ductus arteriosus dramatically and permanently disappeared. A transient reduction in renal function was observed in two infants in whom sustained ill-effects did not occur. The observation that constriction and closure of the patent ductus arteriosus may be induced pharmacologically raises important possibilities for the improved treatment of the respiratory-distress syndrome.

Frank-Starling relationship as an important determinant of fetal cardiac output.

The importance of the Frank-Starling mechanism was evaluated in seven chronically instrumented fetal lambs (128-141 days gestation). Continuous determinations of left ventricular (LV) internal dimensions and pressures were obtained while LV end-diastolic diameter (LVEDD) was reduced by superior vena cava occlusion and increased by infusion of fetal blood into left atrium. A highly significant relationship was found to exist between stroke volume and LV extent of shortening (delta D) (r = + 0.99, P less than 0.001). Altering LVEDD from 10,5 to 13mm or LV end-diastolic pressure from 2.5 to 8 mmHg resulted in a 68% augmentation, in delta D. Spontaneous respiratory efforts resulted in frequent beat-to-beat variations in LVEDD and delta D, which maintained cardiac output constant over a wide range of respiratory rates. Moreover, LV output determined by indicator-dilution techniques remained unchanged over a wide range of spontaneous heart rates (114-180 beats/min) as a result of changes in delta D appropriate to alterations in LVEDD. Thus, changes in resting myocardial fiber length are of fundamental importance in fetal cardiovascular homeostasis and, within physiologic limits, it is quite clear that the Frank-Starling mechanism is operative and effective in the fetal lamb;