Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.

Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first-degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein's anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.

Postnatal atresia of extraparenchymal pulmonary veins, fulminant necrotizing pulmonary arteritis and elevated circulating immune complexes.

An infant with operatively corrected total anomalous pulmonary venous connection developed postnatal atresia of the extraparenchymal left pulmonary veins with secondary arteritis of the ipsilateral intraparenchymal pulmonary arteries. Atresia of the right or left main pulmonary veins or of the common pulmonary vein is a rare occurrence and it is believed that association of such with necrotizing pulmonary arteritis has never been reported. This case illustrates the potential consequences of severe pulmonary venous obstruction in the absence of a left to right shunt.

Children with heart murmurs: can ventricular septal defect be diagnosed reliably without an echocardiogram?

OBJECTIVES: This study was undertaken to determine the accuracy of expert examination for ventricular septal defect (VSD) among children with a heart murmur. BACKGROUND: Because the frequency and nature of errors that might be made by reliance solely on expert examination for diagnosis of VSD are speculative, the role of echocardiography in such diagnosis is controversial. METHODS: Two hundred eighty-seven consecutive previously unevaluated pediatric subjects were enrolled in the study. For each child, the pediatric cardiologists prospectively recorded a working diagnosis and their level of confidence in the diagnosis, categorizing any VSD diagnosed as small or moderate to large. After echocardiography, VSDs were subcategorized by location and requirement for treatment as minor, intermediate or major. Receiver-operating characteristic (ROC) curves described the accuracy of the clinical examination. RESULTS: Seventy-three subjects had a VSD (minor in 52, intermediate in 10 and major in 11). ROC areas (1.0 = perfect discrimination, 0.5 = indiscriminate) were minor VSD 0.92 +/- 0.02 and major/intermediate VSD 0.69 +/- 0.07 (p = 0.0016). Four of 52 minor VSDs were not identified at any level of suspicion; the clinical diagnoses were moderate to large VSD in two patients and atrial septal defect and unlimited differential diagnosis in one patient each. Fourteen of 235 patients without a minor VSD were believed with confidence to have a small VSD, but the final diagnosis was intermediate VSD in 4, innocent murmur in 3, major VSD in 2, pulmonary stenosis in 2 and subaortic membrane, atrial septal defect and mitral regurgitation in 1 patient each. CONCLUSIONS: Almost all minor VSDs are recognized without echocardiography; however, errors can occur even when an expert examiner is confident. Clinical recognition of an intermediate or major VSD is less accurate than clinical recognition of a minor VSD. Failure to distinguish VSDs of major or intermediate importance from minor VSDs is a weakness of the expert clinical examination.

Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study.

OBJECTIVES: The purpose of this study was to determine long-term outcome in adults with congenitally corrected transposition of the great arteries (CCTGA), with particular emphasis on systemic ventricular dysfunction and congestive heart failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF being relatively common in older adults. METHODS: Retrospective analysis of records of 182 patients from 19 institutions were reviewed to determine current status and possible risk factors for systemic ventricular dysfunction and CHF. Factors considered included age, gender, associated cardiac defects, operative history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular) regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were common in groups with or without associated cardiac lesions. By age 45, 67% of patients with associated lesions had CHF, and 25% of patients without associated lesions had this complication. The rates of systemic ventricular dysfunction and CHF were higher with increasing age, the presence of significant associated cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of any type, and particularly with tricuspid valvuloplasty or replacement. Aortic regurgitation (a previously unreported problem) was also relatively common in this patient population. CONCLUSIONS: Patients with CCTGA are increasingly subject to CHF with advancing age; this complication is extremely common by the fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular regurgitation is strongly associated with RV (anatomical right ventricle connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction and CHF; whether it is causative or a secondary complication remains speculative.

Ligation of patent ductus arteriosus in premature infants: importance of accurate anatomic definition.

The aortic arch anatomy of the premature infant may not be as simple to determine as the anatomy of an older child. A case of a premature infant who had inadvertent ligation of the left pulmonary artery during attempted ligation of a patent ductus arteriosus is described. On the fourth day following the initial operation, the patient underwent successful surgery to remove the pulmonary artery ligature and to ligate the persistent patent ductus arteriosus. A lung scan on the seventh day following removal of the pulmonary artery ligature showed normal perfusion of both lungs. Six months later, the child's growth, development, and chest roentgenogram were normal.

Electrophysiologic effect of digitalis on sinoatrial nodal function in children.

Despite the prevalence of digitalis usage in children, the electrophysiologic effects of digitalis on sinoatrial (S-A) nodal function is unknown in this age group. The purpose of this study was to determine the effect of digitalis on sinoatrial conduction time as well as on S-A nodal automatically. Ten subjects (mean age 10.5 years) underwent electrophysiologic assessment of S-A nodal function before and 30 minutes after administration of ouabain (0.01 mg/kg). Total S-A conduction time increased in each subject and the mean value after ouabain (182 msec +/- 13 standard errors of the mean [SEM]) was significantly higher (P less than 0.01) than before (149 msec +/- 11). The sinus cycle length was variable after ouabain (P greater than 0.1). The corrected sinus nodal recovery time also was variable (P greater than 0.1), decreasing substantially in three subjects. Mechanisms of the effect of digitalis on the S-A node and atrium are proposed and discussed. It is concluded that digitalis prolongs the S-A conduction time in children with normal S-A nodal function. By prolonging the S-A conduction time, digitalis may artifactually shorten corrected S-A nodal recovery time in some patients.

Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia in children and adolescents without structural heart disease. Pediatric EP Society, Radiofrequency Catheter Ablation Registry.

Since 1990, management options available for children with paroxysmal supraventricular tachycardia (PSVT) have included radiofrequency catheter ablation (RCA). To determine the efficacy and safety of the procedure and to maintain a database for long-term follow-up, the Pediatric Electrophysiology Society began a Pediatric RCA Registry on January 1, 1991, to which 46 centers have submitted data from 4,135 total children and adolescents (patient age 0.1 to 20.9 years) who underwent 4,651 RCAs (through September 15, 1996). Of the 88% with a structurally normal heart, PSVT mechanisms (n = 4,030) included 3,110 accessory pathways and 920 atrioventricular node reentry tachycardia (AVNRT) during 3,653 procedures for 3,277 patients. During the 7 years of the Registry, analysis of indications for the procedure has shown a gradual shift. During the first year of the Registry for this PSVT group, "medically refractory tachycardia" was listed as the indication for 44% and "patient choice" was listed as 33%, compared with 29% and 58%, respectively, for the years 1995 to 1996 (p <0.005). Registry results were: 90% immediate success for accessory pathways (95% for left lateral; 87% for septal; 86% for right free wall) and 96% for AVNRT; mean fluoroscopy time 47.6 +/- 40 SD minutes; procedure time 257 +/- 157 SD minutes; major complication rate at the time of the procedure 3.2%. Procedure-related deaths included 1 immediate and 3 at 2, 12 and 68 weeks after the procedure (2 were infants). Follow-up revealed 77% and 71% freedom from recurrence at 3 years for accessory pathways AVNRT, respectively, and rare (<1%) detection of additional complications. RCA has evolved into a standard management option for PSVT in children with a structurally normal heart. RCA for children and adolescents should be recommended after consideration of the procedural risk/benefit compared with that of other management options, the natural history, and individual tolerance/symptoms related to PSVT.

Surgical treatment of supraventricular tachycardia in infants and children.

The technique, indications and results of surgical division of accessory atrioventricular connections in 10 infants and children with drug-resistant supraventricular tachycardia are described. The patients ranged in age from 6 months to 15 years. Four patients had associated congenital heart disease. Division of accessory connections were performed on free wall pathways in nine patients (seven right atrial, two left atrial) and on a septal pathway in one patient. Four patients had both anterograde and retrograde conduction over the accessory connection (manifest Wolff-Parkinson-White conduction) whereas six had only retrograde conduction (concealed Wolff-Parkinson-White conduction). The manifst Wolff-Parkinson-White conduction was abolished by surgical division in all four patients. In 8 of the 10 patients the procedure stopped the attacks of paroxysmal supraventricular tachycardia for follow-up periods ranging from 9 months to 3 1/2 years; no patient receives medication to date.

Elective mapping and surgical division of the bundle of Kent in a patient with Ebstein's anomaly who required tricuspid valve replacement.

A 14 year old girl with Ebstein's anomaly and Wolff-Parkinson-White syndrome without supraventricular tachycardia underwent closure of an atrial septal defect and tricuspid valve commissurotomy. Her postoperative course was complicated by her first episodes of recurrent debilitating paroxysmal supraventricular tachycardia. Severe tricuspid insufficiency with low cardiac output necessitated a repeat intracardiac operation. At reoperation the patient underwent successful tricuspid valve replacement with concomitent cardiac mapping and division of the bundle of Kent. In patients with heart disease requiring intracardiac repair who also have Wolff-Parkinson-White syndrome, elective surgical division of the anomalous bundle is recommended whether or not preoperative attacks of tachycardia have occurred.

Survival following blunt chest impact-induced cardiac arrest during sports activities in young athletes.

Blunt chest impact-induced cardiac arrest on the athletic field (commotio cordis) is not necessarily fatal. The 3 survivors reported here emphasize the importance of recognizing this syndrome so that emergency resuscitative measures are more likely to be implemented promptly, and such catastrophes avoided.

Mechanisms of cardiac arrhythmias after the Mustard operation for transposition of the great arteries.

To determine the mechanisms of the cardiac arrhythmias frequently seen after the Mustard operation for transposition of the great arteries, intracardiac electrophysiologic studies were performed in 52 children 1 to 8 years after the Mustard operation. Sinus nodal automaticity as judged from the response to rapid atrial pacing was abnormal in 28 of the 52 children. Sinoatrial conduction (conduction of the sinus impulse to the atrium) was found to be abnormal in three of nine patients studied with the atrial extrastimulus method. Conduction of the sinus impulse from the high right atrium to the atrioventricular (A-V) node was abnormally delayed in only 2 of 41 subjects. The low lateral wall of the right atrium was depolarized late in 3 of 11 subjects (including the preceding 2). Two subjects showed delayed A-V nodal conduction and one delayed His-Purkinje conduction. The mechanism of supraventricular tachycardia induced in the laboratory was determined to be sinoatrial nodal reentry in four subjects and atrial muscle reentry in four. Two of the four with atrial muscle reentry had prolonged high right atrium to low lateral right atrium intervals during sinus rhythm. Thus, damage to the sinus node remains the most common cause of arrhythmias after the Mustard operation. In addition, delayed atrial conduction may predispose to atrial muscle reentrant tachycardia.

Sustained ventricular tachycardia after repair of tetralogy of Fallot: new electrophysiologic findings.

Ventricular arrhythmia originating from the outflow tract of the right ventricle is a presumed cause of late sudden death in patients after repair of tetralogy of Fallot. Exercise testing has been shown to enhance detection, and phenytoin has been shown to control ventricular arrhythmias in these patients. This study reports new findings in 3 patients who underwent electrophysiologic studies at postoperative cardiac catheterization; in each, sustained ventricular tachycardia was induced and found to originate from the inflow-septal area of the right ventricle. Using serial studies, the same sustained ventricular tachycardia was induced during therapeutic serum concentrations of phenytoin but not after propranolol. No patient had ventricular arrhythmia during a 24-hour electrocardiogram or during exercise. Although no patient had normal hemodynamic function, only 1 patient had right ventricular pressure greater than two-thirds systemic pressure. Each patient had undergone initial intracardiac repair at a relatively late age (3, 9, and 9 years).

The learning curve for radiofrequency ablation of tachyarrhythmias in pediatric patients. Participating members of the Pediatric Electrophysiology Society.

The results of radiofrequency ablation for treatment of supraventricular tachyarrhythmias have been reported to improve with increasing experience; however, the precise nature of the learning curve in children is unknown. From November 1990 to October 1993, 1,546 consecutive procedures from the Pediatric Radiofrequency Ablation Registry were categorized into deciles based on number of prior pediatric procedures at the submitting institution. Negative exponential models were tested for strength of relation between volume of prior experience and 4 measures of outcome: success rate, complication rate, fluoroscopy time, and procedure time. Negative exponential curves described the experience-outcome relations well (r = 0.81 to 0.97). Learning rates were most rapid for successful ablation of left free wall accessory pathways, and slowest for right free wall pathway ablation. These models suggest that, given enough experience, procedural success rates > 90% (regardless of pathway location) and fluoroscopy and procedure times averaging < 40 minutes and 250 minutes, respectively, can be achieved in pediatric patients.

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.

Serum concentrations of prostacyclin and thromboxane in children before, during, and after cardiopulmonary bypass.

Twenty-six consecutive pediatric patients undergoing reparative procedures necessitating cardiopulmonary bypass were prospectively studied to determine changes in serum levels of 6-keto-prostaglandin F1 alpha and thromboxane B2. Cardiac lesions included acyanotic lesions (five patients), obstructive lesions (10 patients), and right-to-left shunts (11 patients). There was a significant (p less than 0.05) increase in 6-keto-prostaglandin F1 alpha from preoperative levels measured at the time of arterial and venous cannula insertion. This concentration was maintained throughout cardiopulmonary bypass and remained significantly elevated (p less than 0.001) in the recovery room, but returned to preoperative levels by the morning after the operation. Preoperative levels of thromboxane B2 varied widely and were not significantly different from intraoperative levels. The postoperative levels of thromboxane B2, however, were significantly different (p less than 0.05) from the intraoperative levels. In the pediatric age group undergoing cardiopulmonary bypass, 6-keto-prostaglandin F1 alpha and thromboxane B2 change during bypass but do not significantly differ when preoperative levels are compared to postoperative values.

Taussig-Bing anomaly: total repair with closure of ventricular septal defect through the pulmonary artery.

Total surgical repair of a Taussig-Bing malformation in an 8-year-old boy was accomplished successfully after previous palliative procedures. The child had undergone a Rashkind septostomy when he was 10 days old, banding of the pulmonary artery and division of a patent ductus arteriosus when he was 2 weeks old, and a Blalock-Hanlon septectomy when he was 1 year old. Complete repair involved patching the ventricular septal defect (VSD), debanding and patching the pulmonary artery, and rerouting the venous return by performing a Mustard procedure. Because of its high location, the VSD could not be reached properly through the tricuspid valve and was approached through the pulmonary arteriotomy. Excellent exposure was obtained by retracting the pulmonary valve, and patch closure of the defect was achieved without difficulties. We believe this approach to the VSD is preferable because no incision is necessary in the right ventricle. This is important since the right ventricle becomes the systemic ventricle after the Mustard operation.

Valve replacement in the right side of the heart in children: long-term follow-up.

Twenty-five patients (16 male, 9 female) underwent right-sided valve replacement (10 pulmonary valve replacement, 14 tricuspid valve replacement, 3 tricuspid plus pulmonary valve replacement, and 2 replacements of a single atrioventricular valve) at the University of Nebraska Medical Center from June 1977 to December 1986. Twenty-one patients (84%) are long-term survivors with 2,035 months follow-up (range, 41 to 143 months; mean, 96.9 months). Twenty-three Carpentier-Edwards bioprosthetic valves, one Ionescu-Shiley bioprosthetic valve, and nine St. Jude Medical valves were inserted. Follow-up of 17 patients with a Carpentier-Edwards valve ranged from 5 years 9 months to 11 years 9 months (mean, 8 years 11 months). To date there has been one reoperation after 3 years 4 months in this group. One patient who received an Ionescu-Shiley bioprosthesis required re-replacement at 20 months after operation. Three of 4 patients who received St. Jude mechanical valves and are long-term survivors have required replacement after 36 to 56 months. We conclude that the Carpentier-Edwards bioprosthetic valve is a viable option in the right side of the heart in the young age group when annular size is adequate to accommodate an appropriate bioprosthesis.

Changing indications for pacemakers in children.

Permanent pacemakers were implanted in 50 children. Indications were symptomatic sinus node dysfunction in 34 (68%), surgical block in 9 (18%), and congenital block in 7 (14%). Twenty-three (68%) of the 34 children with sinus node dysfunction had undergone prior cardiac operations. Only 4 of the 50 patients (8%) had electrode problems after a mean pacing time of 29.5 months (range, 1 to 96 months). All 35 of the mercury-cell pulse generators used in 28 patients ceased to function after an average useful life of 20.8 months (range, 1 to 51 months). The lithium-powered units in the 45 survivors all show satisfactory pacing after 5 to 44 months (mean, 28.1 months). With improved pacemaker technology, longer survival after complex repairs, and better monitoring techniques, the indications for cardiac pacing in children have broadened. Surgical block now is an indication in only a small fraction of the pediatric pacemaker population. Sinus node dysfunction accounts for an ever-increasing majority of the pacemakers we currently implant in children.

Epicardial corkscrew lead fracture: an underreported cause of pacing failure?

Three children with a pacemaker sustained similar lead fractures within a two-year period. Each fracture occurred in the corkscrew portion of a Medtronic Model 6917 epicardial lead. All patients were boys. The leads had been in place for 12, 45, and 43 months prior to fracture. None of the patients had sustained major trauma. Fracture of the corkscrew lead has been considered an uncommon complication. However, three lead fractures in the corkscrew area in a population of 60 children followed at this institution indicate that this may be a more common cause of pacemaker-system malfunction than previous data suggest. A plea is made for reporting all pacing failure to the manufacturer.