Catheter ablation of a right atrial appendage to the right ventricle connection in a neonate.

A neonate with incessant supraventricular tachycardia refractory to multiple antiarrhythmic medications was referred to our institution for radiofrequency ablation. An unusual accessory pathway between the right atrial appendage and right ventricle was successfully ablated. This case also emphasizes the congenital origin of such an accessory pathway.

Is arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias.

BACKGROUND: Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. METHODS AND RESULTS: Children aged

Major coronary artery anomalies in a pediatric population: incidence and clinical importance.

OBJECTIVES: We sought to prospectively determine the incidence and clinical significance of major coronary artery anomalies in asymptomatic children using transthoracic two-dimensional echocardiography. BACKGROUND: Anomalous origins of the left main coronary artery (ALMCA) from the right sinus of Valsalva or anomalous origins the right coronary artery (ARCA) from the left sinus are rarely diagnosed in children and can cause sudden death, especially in young athletes. Because most patients are asymptomatic, the diagnosis is often made post mortem. No study to date has prospectively identified anomalous coronary arteries in asymptomatic children in the general population. METHODS: After serendipitously identifying an index case with ALMCA, we examined proximal coronary artery anatomy in children with otherwise anatomically normal hearts who were referred for echocardiography. In those diagnosed with ALMCA or ARCA, we performed further tests. RESULTS: Within a three-year period, echocardiograms were obtained in 2,388 children and adolescents. Four children (0.17%) were identified with anomalous origin of their coronary arteries, and angiograms, exercise perfusion studies and/or stress tests were then performed. One ARCA patient had decreased perfusion in the right coronary artery (RCA) perfusion area and showed ventricular ectopy on electrocardiogram (ECG) at rest that diminished but did not resolve with exercise. A second patient with ALMCA had atrial tachycardia immediately after exercise, with inferior and lateral ischemic changes on ECG and frequent junctional and/or ventricular premature complexes both at rest and recovery. CONCLUSIONS: This study demonstrates that although anomalous origins of coronary arteries are rare in asymptomatic children, the prevalence is greater than that found in other prospective studies. Ischemia can occur with both ALMCA and ARCA even though patients remain asymptomatic. Because of the high risk of sudden cardiac death, aggressive surgical management and close follow-up are necessary.

Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela.

OBJECTIVE: We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND: Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS: A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS: Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS: Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require close follow-up not only of their cardiac rate and rhythm, but also ventricular function.

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease.

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.

Corrected QT interval (QTc) prolongation and syncope associated with pseudohypoparathyroidism and hypocalcemia.

An adolescent presented with exercise-associated syncope and electrocardiographic corrected QT interval (QTc) prolongation. Pseudohypoparathyroidism-induced hypocalcemia was diagnosed. The QTc (485 to 505 milliseconds) shortened during normalization of calcium levels, and syncope has not reoccurred.

Intermediate-term results in pediatric aortic valve replacement.

BACKGROUND: Aortic valve replacement (AVR) in children is now more commonly performed with human tissue valves. METHODS: The results of 100 consecutive pediatric AVRs (50 mechanical, 50 human) were reviewed. RESULTS: There were five perioperative deaths in the mechanical group and one in the human group (p = 0.2). Late complications in the mechanical group included 4 late deaths, 2 cases of endocarditis, 3 thromboembolic complications, and 10 reoperations on the aortic valve. In the human group, there were no late deaths, 2 reoperations for allograft aortic valve deterioration (both in Marfan's patients), and 1 reoperation for allograft pulmonary valve stenosis. Four-year actuarial survival was 83% in the mechanical group and 98% in the human group (p = 0.02). Four-year actuarial survival free of all valve-related complications was 61% in the mechanical group and 88% in the human group (p = 0.008). CONCLUSIONS: Human valves in children requiring AVR provide superior intermediate-term survival and freedom from valve-related complications compared to mechanical valves. Marfan's syndrome may represent a rare remaining contraindication for human AVR in children.

A case for routine screening of coronary artery origins during echocardiography: fortuitous discovery of a life-threatening coronary anomaly.

Anomalous origin of the left main coronary artery from the right sinus of Valsalva with retropulmonary course is a rare congenital abnormality. It is associated with a high incidence of sudden cardiac death, particularly among young, athletic individuals. Many of these individuals do not have symptoms before sudden death, and the diagnosis is usually made at postmortem examination. We present a case of a 15-year-old boy who was evaluated for a systolic click with routine 2-dimensional echocardiography. The anomalous coronary artery was serendipitously identified, allowing surgical intervention. Coronary artery origin and proximal course should be visualized on routine echocardiography in the pediatric population.

Left-sided atrioventricular nodal ablation using the transseptal approach: clinico-histopathologic correlation.

To our knowledge, prograde access to the left ventricle to perform a left-sided AV node (AVN) ablation has not been reported. We present the case of a patient with Noonan's syndrome and supravalve aortic stenosis who required aortic valve replacement with a mechanical valve. Due to chronic atrial fibrillation, a transvenous pacing system was implanted and transcatheter radiofrequency ablation of the AVN was performed. Attempts at right-sided AVN ablation were unsuccessful. Due to the presence of the mechanical aortic valve, a left-sided AVN ablation was performed successfully using the transseptal approach. The patient died suddenly 6 months after the procedure, and the histologic study of the heart is reported.

Effect of age and surgical technique on symptomatic arrhythmias after the Fontan procedure.

The purpose of this study was to determine the effects of newer Fontan modifications (lateral tunnel with or without fenestration) and patient's age at surgery on the incidence and impact of symptomatic postoperative early and intermediate arrhythmias. Modifications to the Fontan procedure are used to decrease postoperative complications, and the Fontan procedure is now being performed on younger patients to reduce age-related changes in ventricular function. A retrospective review was done of the medical records of 151 consecutive patients, ranging in age from 1 to 49 years, who underwent a Fontan procedure at Texas Children's Hospital between 1987 and 1993. Risk factors were identified for early and intermediate arrhythmias. Age at time of the procedure was an independent predictor of early atrial arrhythmias (p = 0.03), ventricular arrhythmias (p = 0.003), and junctional ectopic tachycardia (JET) (p = 0.05). We found that the older the patient at surgery, the higher the incidence of atrial and ventricular arrhythmias, whereas the younger the patient, the higher the incidence of JET. Using Cox's proportional-hazards model, the risk of intermediate atrial arrhythmias after lateral tunnel modification was 1/3 that after atriopulmonary connection. Younger patients who underwent the Fontan procedure had a lower risk for early atrial and ventricular arrhythmia but an increased risk for JET. The lateral tunnel modification can be performed in order to reduce the risk of intermediate atrial arrhythmias.

Postinfarction ventricular arrhythmias in children.

Because limited information is available on significant arrhythmias after myocardial infarction in pediatric patients, this study was performed to determine the incidence and impact of ventricular tachycardia or fibrillation on the postinfarction course in patients aged 1 day to 16 years. Review of 96 such children showed a wide range of underlying heart disease (56 patients with congenital heart disease, 12 with cardiomyopathy, and 28 with acquired heart disease). Postinfarction ventricular tachycardia/fibrillation occurred commonly (28% of patients with acute myocardial infarction) and early (84% by 2 days after diagnosis). Postinfarction mortality was high in patients with acute myocardial infarction (61%) and appeared to be independent of type of associated heart disease. Ventricular tachycardia/fibrillation was associated with higher mortality rates (approximately 80%) in patients with acute or remote myocardial infarction. The 61 postinfarction survivors were monitored for an average of 4.9 years, and none had significant recurrent ventricular arrhythmias or late sudden death.

Differentiating anomalous left main coronary artery originating from the pulmonary artery in infants from myocarditis and dilated cardiomyopathy by electrocardiogram.

Anomalous left main coronary artery (ALMCA) originating from the pulmonary artery is an important cause of morbidity from heart failure and mortality in infants. Discriminating ALMCA from myocarditis or other forms of dilated cardiomyopathy (DC) in infants is critical for proper early management of this treatable disease. This study was performed to characterize electrocardiographic (ECG) patterns in infants with ALMCA, and to identify features that would allow differentiation of these infants from those with myocarditis/DC. Presenting electrocardiograms from 28 patients with ALMCA < 2 years of age were analyzed for 103 variables, and compared with electrocardiograms from 28 aged-matched infants with myocarditis/DC using the t test, Fisher's exact test, and discriminant analysis using stepwise logistic regression techniques. ECG findings characteristic of infants with ALMCA were confirmed, including deep (> or = 3 mm) and wide (> or = 30 ms) Q waves and a QR pattern in at least 1 of the following leads: I, aVL, V5 to V7. Also, the complete absence of Q waves from leads II, III, and aVF in all infants with ALMCA was noted. These and other ECG patterns were more common in infants with ALMCA than in those with myocarditis/DC (p < 0.05), but were also noted in some patients with myocarditis/DC. Stepwise logistic regression analysis identified 3 ECG variables that best discriminated ALMCA from myocarditis/DC, including Q wave width (w) in lead I, and Q-wave depth (d) and ST-segment amplitude (s) in lead aVL.(ABSTRACT TRUNCATED AT 250 WORDS)

Lifelong management of patients with a single functional ventricle: a protocol.

Of the wide variety of congenital heart defects, the single functional ventricle continues to be one of the most enigmatic. Compared with patients who have complex congenital heart defects and 2 functional ventricles, patients with a single functional ventricle have greater surgical and long-term morbidity and mortality, and use more medical resources. Recent investigations have shown that patients with a single functional ventricle often have very satisfactory hemodynamics soon after a modified Fontan repair but then develop dilated cardiomyopathy during the subsequent decade. The cause and pathogenesis of the cardiomyopathy have not yet been determined. Many publications have examined individual aspects of the care of these patients based on retrospective reviews, but very few have provided comprehensive prospective methods for managing patients with a single functional ventricle. We hypothesized that a comprehensive management protocol with regular review of the results would provide a better understanding of the problems encountered in these patients and thus improve long-term outcome. Herein, we present our initial protocol for the lifelong management of patients with a single functional ventricle.

Effect of T3 on insulin action, insulin binding, and insulin receptor kinase activity in primary cultures of rat hepatocytes.

In vivo studies have demonstrated that the liver is the main site of insulin resistance in hyperthyroidism. To further investigate the effect of thyroid hormone in the liver, we have incubated primary cultures of rat hepatocytes in the presence and absence of triiodothyronine (T3) 1 ng/ml and 5 ng/ml for 20 hr. Without affecting basal activity, T3 5 ng/ml decreased insulin-stimulated (1 x 10(-7) M) lipid synthesis but not insulin-stimulated alpha-aminoisobutyric acid uptake. These changes occur in the absence of any abnormalities in 125I-insulin binding, degradation, internalization or insulin receptors structure as determined by affinity-labeling methods. However, basal insulin receptor kinase activity using Glu4: Tyrl as phospho-acceptor was decreased by T3 without altering its insulin responsiveness. These results demonstrate the heterogeneity of T3's effects at the postinsulin binding level in the liver.

Insulin resistance in uremia: insulin receptor kinase activity in liver and muscle from chronic uremic rats.

We have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the beta-subunit and insulin receptor kinase activity using Glu80, Tyr20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristic of the receptors, as determined by electrophoretic mobilities of affinity labeled alpha-subunit and the phosphorylated beta-subunit, were normal in uremia. 125I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus our data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase.

Is glycosylation in the liver needed for insulin binding, processing, and action? Evidence for heterogeneity.

Incubation of primary cultures of rat hepatocytes with tunicamycin (1 microgram/ml) for 16 h inhibits de novo glycosylation by more than 90%, yet 50% of initial 125I-insulin binding is still present. The remaining insulin-binding activity is to glycosylated receptors, since they are adsorbed and specifically desorbed from wheat germ agglutinin-Sepharose. Furthermore, there is no difference in the molecular weight size of the alpha-subunit of the insulin receptors either in normal or tunicamycin-treated hepatocytes as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 125I-insulin receptor cross-linked with disuccinimidyl suberate. This gives us an opportunity to study the function of these glycosylated insulin receptors in cells where de novo glycosylation is inhibited. Inhibition of de novo glycosylation decreases receptor-mediated 125I-insulin internalization and degradation. The tunicamycin-treated cells are totally resistant to insulin with regard to [14C]aminoisobutyric acid uptake. In contrast, there is normal stimulation of [14C] acetate and [14C]glucose incorporation into lipids and glycogen by a maximal concentration of insulin. The interpretation of these data is, however, complicated by the fact that tunicamycin markedly inhibits basal lipid synthesis without altering basal glycogen synthesis or [14C]aminoisobutyric uptake. These results demonstrate the heterogeneity of the postinsulin binding system in the liver. Besides glycosylation of the insulin receptor, which is needed for insulin binding, other cellular glycoproteins are important for insulin processing as well as mediation of some, but not all, of the biological actions of insulin. The nature of these liver glycoproteins and their relationship to the insulin receptor have not yet been defined.

Chemical mediator of insulin action stimulates lipid synthesis and down regulates the insulin receptors in primary cultures of rat hepatocytes.

Incubation of rat liver particulate fraction with insulin causes the release of a substance that stimulates lipid synthesis and down regulates the insulin receptor in primary cultures of isolated rat hepatocytes. This substance may be similar to putative mediator(s) of insulin action which has been shown to modulate the activity of key enzymes of lipid and carbohydrate metabolism in various cell free systems. Our data demonstrate that the mediator of insulin is also biologically active in an intact cell system. Down regulation of the insulin receptor by the mediator supports the concept that this phenomenon is a post binding event of insulin action.