Ventricular inversion with normal ventriculoarterial connection and left atrial isomerism: correction by the Mustard operation.

A 2 year old boy with ventricular inversion and normal ventriculoarterial connection is described. Associated cardiac lesions included single atrium, absence of the coronary sinus, bilateral superior venae cavae, absence of the hepatic segment of the inferior vena cava with azygos and hemiazygos continuation, right aortic arch, levocardia and left atrial isomerism. At 5 days of age, the patient underwent a Waterston (aortopulmonary) anastomosis because of suspected pulmonary atresia. The correct diagnosis was established at 2 years of age and the patient had a successful Mustard operation (interatrial baffle procedure) and closure of the Waterston anastomosis. Accurate preoperative diagnosis is difficult in this rare cardiac anomaly and the reported mortality rate is high.

Ventricular septal defect associated with aneurysm of the membranous septum.

The most common variety of ventricular septal defect, a perimembranous defect, is frequently associated with a so-called aneurysm of the membranous septum. Previous studies have suggested that ventricular septal defects associated with an aneurysm of the membranous septum tend to spontaneously decrease in size or close more than defects without such an aneurysm. To better define the natural history of this entity, clinical and catheterization data from 87 patients with ventricular septal defect and aneurysm of the membranous septum were reviewed. The initial evaluation was made at a median age of 0.3 years (range 0.1 to 11), with the final evaluation at a median age of 10 years (range 1.5 to 20) and a median duration of follow-up of 8.6 years (range 1.2 to 18.8). Approximately 75% of the ventricular septal defects had a small or no left to right shunt at last evaluation. Overall, 48 patients (55%) had no significant change in the size of the defect, and 39 (45%) showed improvement during the period of observation. Only four patients (5%) had spontaneous closure of the defect. Of the 49 patients who presented with a large left to right shunt, with or without congestive heart failure, 23 (47%) had persistence of a shunt large enough to warrant surgery. When spontaneous improvement occurred, it did so by 6 years of age in all but one patient. Therefore, a continued tendency for a ventricular septal defect associated with an aneurysm of the membranous septum to spontaneously decrease in size or close after this age may be less likely than previously suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias and Stokes-Adams attacks in acute rheumatic fever.

In spite of general complacency about first-degree heart block in acute rheumatic fever, abnormal conduction with dysrhythmias, occasional complete heart block, and, rarely, Stokes-Adams attacks are important early signs of acute rheumatic fever and may precede other signs. Every person with episodic fainting is entitled to an ECG, and frequent ECGs are imperative in any case of rheumatic fever with signs of arrhythmias. Changing atrioventricular block necessitates continuous monitoring for dysrhythmias. A 13-year-old boy who appeared with Stokes-Adams attacks secondary to acute rheumatic fever was successfully treated by temporary pacing.

Experience with heart transplantation in children.

Between March 1981 and March 1986, 200 orthotopic heart transplantations were performed at the University of Pittsburgh. Fourteen of those procedures were carried out in children 2 to 16 years of age. Two children received combined liver and heart transplants; one because of familial hypercholesterolemia with associated ischemic heart disease, and the other because of dilated cardiomyopathy associated with intrahepatic biliary atresia. Eight patients had dilated cardiomyopathy, and two had myocarditis. Two had heart transplantations for congenital heart disease: one had multiple muscular ventricular septal defects repaired in infancy and had an associated cardiomyopathy, and the other developed a cardiomyopathic ventricle from a congenital right coronary artery to right atrial fistula. Chronic immune suppression consisted 0.2 to 0.5 mg/kg/d of prednisone and 5 to 50 mg/kg/d cyclosporine, with the addition of antithymocyte globulin for unresolved moderate or severe acute rejection. There were three early postoperative deaths: one from intracranial bleeding, one from Pseudomonas mediastinitis, and one from ischemic injury to transplanted organs. Early postoperative complications included reversible renal failure, hypertension, and seizures. Late problems were related to allograft rejection and side effects of cyclosporine and corticosteroids. Significant rejection episodes occurred in all patients surviving longer than 2 weeks, with seven requiring antithymocyte globulin. Two patients died 8 months following transplantation of severe acute and chronic rejection; another patient required retransplantation for ischemic cardiomyopathy resulting from chronic rejection but subsequently died of recurring rejection 3 months after the second transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic function after the Mustard operation for transposition of the great arteries.

Pre- and postoperative cardiac catheterization data and cinenangiocardiograms of 82 patients who survived the Mustard operation for transposition of the great arteries (TGA) were reviewed. The post-operative catheterizations were performed 20 days to 10 years after operation (mean 2.5 years). Forty-six patients (56%) had no or insignificant associated cardiac lesions, whereas 36 (44%) had ventricular septal defect, pulmonary stenosis, or both, and required surgical intervention at the time of the Mustard operation. Postoperatively, 11 patients (13%) had significant systemic venous obstruction. Of the 11 patients, 6 required reoperation, and 2 patients had evidence of restenosis or complete obstruction in the superior vena cava after reoperation. In most patients, superior vena caval obstruction was well tolerated even in the presence of high pressure in the superior vena cava. Pulmonary venous obstruction occurred in 5 patients (6%), 3 of whom had no clinical symptoms despite severe pulmonary venous obstruction, although all had radiographic evidence of pulmonary venous congestion. The incidence of obstruction was drastically reduced after the Mustard operation was modified to include routine enlargement of the pulmonary venous atrium. Tricuspid regurgitation was uncommon (10%), but did occur in patients who had transatrial closure of a ventricular septal defect. Preoperatively, left ventricular outflow obstruction occurred in 38%. In 12 patients an attempt was made to relieve the obstruction at surgery. The 6 patients who had localized obstruction had a good result, but patients with more diffuse narrowing of left ventricular outflow had little or no relief of obstruction. Mild to moderate left ventricular outflow gradients regressed spontaneously in most patients after the Mustard operation.

Rest and exercise right and left ventricular function late after the Mustard operation: assessment by radionuclide ventriculography.

To evaluate ventricular function late after atrial repair of transposition of the great arteries (TGA), 26 asymptomatic patients had rest and exercise radionuclide ventriculography performed a mean of 9 years (range 5 to 15) after undergoing the Mustard operation. The mean resting right (systemic) ventricular (RV) ejection fraction (EF) was 0.50 +/- 0.10 (+/- 1 standard deviation); the RVEF was less than 0.45 in 8 patients. With exercise the RVEF increased in 9 patients and either failed to increase or decreased in 15 (including all 8 patients with resting values less than 0.45). The weight-adjusted work load performed was a first predictor of RV exercise response (sensitivity 87%, specificity 92%); patients whose RVEF increased did more work. The mean resting left (pulmonary) ventricular (LV) EF was 0.58 +/- 0.09; the LVEF was less than 0.50 in 3 patients. With exercise the LVEF increased in 14 patients and did not increase in 10 (including all 3 with resting values less than 0.50). The presence of complex ventricular arrhythmia documented on Holter monitoring was a first predictor of failure of the LVEF to increase with exercise (sensitivity 84%, specificity 71%). The patient's age, operative age, postoperative interval, residual arterial desaturation, preoperative large ventricular septal defect or pulmonary stenosis, postoperative pulmonary stenosis or superior vena caval obstruction, or performance of a second open-heart procedure was predictive of the rest or exercise EF of either ventricle.

Arrhythmias in transposition of the great arteries after the Mustard operation.

Disorders of rhythm or conduction in patients with transposition of the great arteries (TGA) after the Mustard operation have been widely reported. This study provides a systematic evaluation of the electrophysiologic function of 87 survivors of the Mustard operation at a single institution. Surface electrocardiograms were reviewed in all 87 patients, Holter monitoring data in 26 patients, exercise electrocardiograms in 21 patients, and invasive electrophysiologic data in 61 patients. Surface electrocardiograms showed normal sinus rhythm in 52%, sinus node dysfunction in 27%, and atrioventricular block in 16%. Holter monitoring was obtained in an unselected subgroup of 26 patients who had a mean age of 12 years and a mean interval from operation of 9 years. Sinus node dysfunction was found in 58%, atrioventricular block in 27% ventricular ectopy in 50%, supraventricular ectopy in 27%, and no abnormalities in only 8%. Intracardiac electrophysiologic evaluation showed a high frequency of abnormal sinus node recovery times and suboptimal response of the atrioventricular-conduction system to rapid atrial pacing. When all modalities used in this study were considered, sinus node dysfunction occurred in 47%, ectopy in 34% and atrioventricular block in 23%. Although only 30% of patients had no evidence of arrhythmia, symptoms of rhythm or conduction disturbances were rare.

Electrocardiogram in double chamber right ventricle.

Thirty patients with a double chamber right ventricle were seen during a 7 year period. The majority of patients had associated cardiac anomalies, most commonly a ventricular septal defect. In this series, as in others, the history, clinical examination, chest roentgenogram and echocardiogram were inconclusive for diagnosing double chamber right ventricle. Symptoms were generally related to the severity of the associated anomalies. In 40 percent of the patients reviewed, upright T waves were found in lead V3R as the only electrocardiographic finding suggestive of right ventricular hypertrophy. Because upright T waves in lead V3R in the absence of other evidence of right ventricular hypertrophy are not commonly seen in patients with an isolated ventricular septal defect or a defect associated with other forms of right ventricular outflow obstruction, this finding should alert the cardiologist to the possibility of the presence of double chamber right ventricle prior to cardiac catheterization.

Absent right superior vena cava with persistent left superior vena cava: implications and management.

Seven cases of absent right superior vena cava with persistent left superior vena cava and normal situs were diagnosed at Children's Hospital of Pittsburgh. All patients had associated cardiac defects. In two cases the diagnosis was made at autopsy, the first in 1957 and in a 26 day old infant with multiple cogenital defects and the second in 1965 in a 22 day old infant who had pulmonary atresia with ventricular septal defect and patent ductus arteriosus. Since 1966 absent right superior vena cava has been diagnosed at cardiac catheterization in five children. Three of these children have had surgery, two for subaortic stenosis and one for an atrial septal defect. One has an insignificant atrial septal defect and the fifth has a ventricular septal defect. The electrocardiogram of four reveals s short P-R interval and a leftward frontal plane axis of the P wave, suggesting a low atrial focus. None has had any significant conduction problem. All five children are living and well, the oldest has survived 13 years postoperatively. Certain precautions are necessary should corrective cardiac surgery or transvenous pacemaker insertion be necessary.

Echocardiographic findings before and after liver transplantation.

Echocardiographic studies were performed in 73 patients with various types of chronic liver disease. They were 0.5 to 19 years old (mean 5). Thirteen patients underwent follow-up echocardiography 1 to 13 months (mean 6) after liver transplantation. Preoperatively 60 patients (82%) showed evidence of high cardiac output (cardiac index greater than 4 liters/min/m2); these patients manifested increased left ventricular (LV) and left atrial dimensions and a thickened LV posterior wall. Transvenous contrast echocardiographic study confirmed the presence of intrapulmonary arteriovenous shunting in 4 patients. Studies after liver transplantation revealed a reduced LV end-diastolic dimension in 12 patients. Cardiac index was reduced a mean of 35% after transplantation (p less than 0.001). This study suggests that liver transplantation improves common hemodynamic abnormalities in chronic liver disease.

Exercise studies after the Mustard operation in transposition of the great arteries.

Twenty-one postoperative patients with transposition of the great arteries (TGA) underwent graded exercise testing 4 to 15 years (mean 9) after the Mustard operation. No patient had subjective exercise intolerance before testing, although some had symptomatic resting arrhythmias. Correlations were made between cardiac catheterization data and 24-hour ambulatory monitoring. Exercise tolerance was diminished in nearly half of the patients. No statistically significant differences were found in heart rate or blood pressure responses, but maximal oxygen consumption values were lower than the control values (p less than 0.001) in the larger patients. Arrhythmias were present or provoked in most patients during exercise testing. Only 28% remained in normal sinus rhythm during and after exercise. Multifocal premature contractions were the most serious arrhythmias demonstrated. Some long-term survivors of the Mustard operation may have abnormal exercise dynamics, even though they may be asymptomatic and have normal physical activities and endurance. Mean maximal systolic blood pressure, heart rate, oxygen consumption, and maximal treadmill times were consistently in the low-normal range or were statistically lower than normal.

Pneumonectomy for intractable left bronchial compression in d-transposition of the great arteries.

In infants with transposition of the great arteries (TGA) tracheobronchial obstruction may occur as a result of compression by a dilated posterior pulmonary artery, especially if there is a large interventricular septal defect with its attendant large pulmonary blood flow and high pressure. Banding of the pulmonary artery may give temporary relief. A patient with TGA had collapse of the left lung at 2 months of age, following atrial septectomy. Bronchoscopy and bronchography revealed extrinsic compression of the left main bronchus. Banding of the pulmonary artery at 6 months of age relieved the respiratory distress. At 8 years of age atelectasis of the left lung recurred following a Mustard procedure. Two additional procedures were attempted to decrease the pressure of the pulmonary artery on the bronchus but these were unsuccessful. At age 9 years, pneumonectomy, her sixth thoracotomy, was performed as a final attempt to relieve the respiratory problem caused by persistent atelectasis. She is now 17 years of age and has remained asymptomatic during the last 8 years.

Clinical implications of postoperative unilateral phrenic nerve paralysis.

Unilateral phrenic nerve paralysis (PNP) folowed 32 (1.7 percent) of 1,891 consecutive cardiac surgical procedures during an 8 year peroid. Diagnosis was based on radiographic criteria with comparison of preoperative and postoperative chest radiographs and was confirmed in all 21 evaluated by fluoroscopy. Six had persistent radiographic abnormality more than 12 months postoperatively. PNP occurred most frequently in association with Blalock-Taussig shunts. These operations represented 22 percent of this series, and PNP complicated 7 percent of all Blalock-Taussig shunts. PNP was less well tolerated in the 14 infants than in the 18 older children. Eleven infants had serious difficulties during weaning from mechanical ventilatory support. Five infants required tracheostomy, one underwent diaphragmatic plication, and three died. Infants had a mean duration of mechanical ventilation of 24 days and required prolonged intensive care and long-term hospitalization. In comparison, older children had a more benign postoperative course. Diaphragmatic plication should be considered in infants with paradoxical motion of the hemidiaphragm who remain dependent on mechanical ventilatory support for more than 2 weeks postoperatively.

Bilateral ductus arteriosus in d-transposition of the great arteries with right aortic arch.

The rare anomaly of a right aortic arch, distal origin of the left subclavian artery, and posterior left ductus arteriosus (forming a vascular ring) plus a right ductus arteriosus is described in an infant with d-transposition of the great arteries with an intact septum. The presence of a right aortic arch and distal left subclavian artery with bilateral ductus arteriosus has not been described previously.

Discrete subvalvular aortic stenosis. An evaluation of operative therapy.

Angiocardiographic and operative observations support the validity of classifying the spectrum of congenital subvalvular aortic stenosis into a membrane, fibromuscular collar, and tunnel. Our current operative method is to excise a thin membrane or thick fibrous ridge, and, if a fibromuscular collar or tunnel is identified, to effect a left ventricular myomectomy as described by Morrow for hypertrophic subaortic stenosis. Data from experience with 35 children indicate that this approach is effective and safe. Gradients are substantially reduced and residual obstruction acceptable. Successive clinical evaluations (100 percent of 33 survivors) over an interval of 1 to 13 years (mean of 6) affirm that amelioration of the obstruction endures.

Management of bilateral ductus arteriosus in complex cyanotic heart disease.

Bilateral ductus arteriosus (BDA) usually is associated with complex cyanotic heart disease. Since pulmonary valve atresia often is part of the complex, hypoxia may necessitate emergency cardiac catheterization and surgery for these critically ill newborn infants. Optimum management depends on accurate delineation of the intracardiac and great vessel anatomy. Since the ductus arteriosus has a tendency to close spontaneously, the true anatomy of the fourth to sixth aortic arch connections should be determined on the first catheterization. An over-all plan for future care by the medical-surgical team should have been made at the time of the initial surgical procedure. The case histories of four newborn infants with BDA associated with cyanotic heart diseases are reported. The anatomy and basic embryology of the fourth to sixth arch system is reviewed and recommendations for long-term management are given.

Valve replacement in children and adolescents.

Replacement of diseased heart valves has become the treatment of choice in many adults. Valve replacement in older children and adolescents has been done in our institution only when other procedures are ineffective. Over the past 10 years, 24 patients have received 28 artificial valves. Thirteen (54 per cent) had rheumatic heart disease; the remainder had congenital or acquired valvular abnormalities. The Björk-Shiley valve was most commonly used in the aortic position and the Beall prosthesis in the mitral position. Sixteen patients (67 per cent) survived operation and have been followed from 3 to 79 months, averaging 27 months. All are free of cardiac symptoms. Hemarthrosis occurred once in 2 survivors (13 per cent). Eight patients died (33 per cent), 5 immediately postoperatively and 3 within a year after the operation. The mortality rate has declined to 21 percent during the past 3 years. Our experience in the pediatric age group suggests that valve replacement is a serious undertaking with higher mortality rate than in adults. The operation should be reserved for those patients in whom valvuloplasty or valvulotomy is expected to be ineffective.

Surgical management of univentricular heart with subaortic obstruction.

In children with a univentricular heart and a rudimentary subaortic chamber, surgical relief of subaortic obstruction caused by a restrictive bulboventricular foramen is associated with high morbidity and mortality. A 6-year-old child with a univentricular heart of the left ventricular type, a rudimentary subaortic chamber, and atresia of the left-sided atrioventricular valve had pulmonary artery banding in infancy. Severe subaortic obstruction subsequently developed. At operation, the pulmonary artery was transected and the stump was anastomosed directly to the posterior aspect of the ascending aorta, diverting left ventricular blood into the aorta through the pulmonary valve. The distal pulmonary artery was anastomosed side-to-side to the ascending aorta to provide pulmonary blood flow. Cardiac catheterization fifteen months after the operation demonstrated an excellent hemodynamic result. When the pulmonary artery is adequate in size, a bypass operation by way of an anastomosis between the ascending aorta and the pulmonary artery is a relatively safe and effective means of relieving the ventricular outflow obstruction caused by a restrictive bulboventricular foramen.

The role of non-nutritive dietary constituents in carcinogenesis.

Very low levels of a large variety of non-nutritive chemicals occur in the diet. Among those that occur naturally are metabolites of molds (for example, mycotoxins) and bacteria (for example, nitrosamines) and natural constituents of plants (for example, pyrrolizidine alkaloids). Many of these are occasional contaminants, whereas others are normal components of relatively common foods. Some compounds (for example, aflatoxin, nitrosamines, and hydrazones) have been found to be carcinogenic in laboratory animals and mutagenic in bacterial and other systems, thereby posing a potential risk to humans. However, there have been very few definitive epidemiologic studies. Therefore, further investigations are necessary to determine the significance of these experimental findings for humans. It is apparent that many foods naturally contain substances with mutagenic properties and that some substances found in foods can enhance or inhibit the mutagenic activity of other compounds. Furthermore, mutagens can be formed during the cooking or processing of foods. However, caution is needed in the interpretation of these findings. Although mutagens by definition are "suspect" carcinogens, many mutagens detected in foods have not been adequately tested for carcinogenicity, and therefore their significance for human health cannot be fully assessed. With the exception of studies on non-nutritive sweeteners like saccharin and cyclamate, or those on nitrate and nitrite, very few epidemiologic studies have been conducted to examine the effect of food additives on cancer risk. Of the few direct food additives that have been tested and found to be carcinogenic in animals, all except saccharin have been banned from use in the food supply. Minute residues of a few indirect additives that are known either to produce cancer in animals (for example, vinyl chloride and acrylonitrile) or to be carcinogenic in humans (for example, vinyl chloride) are occasionally detected in foods. Thus far, the increasing use of food additives does not seem to have contributed significantly to the overall cancer risk for humans. However, the relatively short duration of use of many of these substances and the inadequacy of the data base preclude definitive conclusions. Very low levels of a large and chemically diverse group of substances--environmental contaminants (for example, residues of pesticides, polycyclic aromatic hydrocarbons, and traces of toxic metals)--may be present in foods.(ABSTRACT TRUNCATED AT 400 WORDS)

A uridine adduct with an ester of the carcinogen 3-hydroxy-1-methylxanthine.

The structure of the uridine adduct with the acetate ester of the carcinogen 3-hydroxy-1-methylxanthine has been determined. Covalent binding is between C-8 of xanthine and O-2 of uracil. This was determined from studies of the NMR spectrum, mass spectra and solvolysis in liquid hydrogen sulfide. The nucleoside adduct, formed with uridine, is identical with the adduct with polyuridylic acid after enzymatic hydrolysis. Treatment with aqueous ammonia or pH 7 at 100 degrees C leads to the loss of ribose. Thymidine also forms an adduct with 3-acetoxy-1-methylxanthine in a similar yield. Model studies with a space-filling model suggest that the methylxanthine moiety can fit into the major groove of DNA and cause minimal helix distortion if the thymine base is rotated into the unnatural syn conformation.