John D. Kugler

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. Ebsteins 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.

Radiofrequency Catheter Ablation for Tachyarrhythmias in Children and Adolescents

Background Although radiofrequency catheter ablation has been used extensively to treat refractory supraventricular tachycardia in adults, few data are available on its safety and efficacy in children and adolescents. We reviewed registry data obtained from 24 centers to evaluate the indications, early results, complications, and short-term follow-up data in young patients who underwent this procedure. Methods Standardized data were submitted for 652 patients who underwent 725 procedures between January 1, 1991, and September 1, 1992. The mean length of follow-up was 13.5 months. Results The median age of the patients was 13.5 years, and 84 percent of them had structurally normal hearts. The initial success rates for ablation of atrioventricular accessory pathways (508 of 615 procedures) and atrioventricular-node reentry (63 of 76 procedures) were both 83 percent. Greater institutional experience in performing ablation in children and location of the accessory pathway in the left free wall correlated with...

Pediatric Radiofrequency Catheter Ablation Registry Success, Fluoroscopy Time, and Complication Rate for Supraventricular Tachycardia: Comparison of Early and Recent Eras

Ablation Outcomes for Supraventricular Tachycardia. Introduction: To assess changes of success rate, fluoroscopy time, and complication rate for six supraventricular tachycardia pathways/mechanisms, data from the Pediatric Radiofrequency Catheter Ablation Registry were grouped into two eras (1991–1995; 1996–1999).

Radiofrequency Catheter Ablation for Paroxysmal Supraventricular Tachycardia in Children and Adolescents Without Structural Heart Disease

Abstract 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

Cardiac Rhythm after the Mustard Operation for Complete Transposition of the Great Arteries

The Mustard operation corrects the effects of congenital transposition of the great arteries by creating an intraarterial baffle to direct pulmonary venous blood to the tricuspid orifice and systemic venous blood to the mitral orifice. To identify the long-term effects of this procedure, we followed 372 patients with complete transposition of the great arteries who survived the Mustard operation for at least three months. The mean follow-up period was 4.5 years (range, 0.4 to 15.9); the mean age at operation was 2.0 years. Mean resting heart rates were consistently lower than those for age-matched normal children. Seventy-six per cent of the patients had sinus rhythm during the year of operation--a figure that decreased to 57 per cent by the end of the eighth postoperative year. Twenty-five patients died during the follow-up period, nine suddenly. Life-table analysis revealed a cumulative survival rate of 91 per cent for 11 years and 71 per cent for 15 years after the operation. No strong risk factor for sudden unexpected death identified. This study demonstrates that extended survival among patients with transposition can be expected after the Mustard operation. However, over time there is a decreasing prevalence of normal sinus rhythm in survivors, as well as a small risk of sudden death.

Ventricular arrhythmias in postoperative tetralogy of Fallot.

Ventricular arrhythmias in patients after total surgical repair of tetralogy of Fallot have been associated with late sudden death. In this large multicenter retrospective study of 359 patients with postoperative tetralogy of Fallot, spontaneous ventricular premature complexes (VPCs) on 24-hour ambulatory electrocardiographic monitoring and laboratory-induced ventricular tachycardia (VT) by electrophysiologic stimulation were analyzed. The mean age at surgical repair was 5 years and the mean follow-up duration after repair was 7 years. Spontaneous VPCs on ambulatory monitoring were found in 48% and induced VT on electrophysiologic stimulation was found in 17% of patients. Both spontaneous VPCs and induced VT were significantly related to delayed age at repair, longer follow-up interval, symptoms of syncope or presyncope and right ventricular systolic hypertension (greater than 60 mm Hg) (p less than 0.05), but not to right ventricular diastolic pressure greater than 8 mm Hg. The VPCs on ambulatory monitoring were more complex with increasing age at repair and follow-up duration. Induction of VT on electrophysiologic stimulation correlated with spontaneous VPCs including VT on 24-hour ambulatory electrocardiographic monitoring. The electrophysiologic stimulation protocol varied and the induction of VT increased with a more aggressive stimulation protocol. While induced sustained monomorphic VT was related to all forms of spontaneous VPCs, induced nonsustained polymorphic VT was related to more complex forms of VPCs on ambulatory monitoring. VT was not induced in asymptomatic patients who had normal 24-hour ambulatory electrocardiographic monitoring and normal right ventricular systolic pressure. (ABSTRACT TRUNCATED AT 250 WORDS)

Inadvertent Atrioventricular Block During Radiofrequency Catheter Ablation Results of the Pediatric Radiofrequency Ablation Registry

BACKGROUND Inadvertent atrioventricular block is a complication of radiofrequency ablation. The present study is an analysis of the incidence, significance, and factors associated with inadvertent atrioventricular block during radiofrequency catheter ablation in childhood and adolescence. METHODS AND RESULTS The records of the Pediatric Radiofrequency Ablation Registry were reviewed. Between January 1, 1991, and April 1, 1994, atrioventricular block occurred in 23 of 1964 radiofrequency ablations (1.2%): 14 as third-degree block (3 transient) and 9 as second-degree block (5 transient). Atrioventricular block occurred from 5 seconds to 2 months (mean, 4.1 days; median, 15 seconds) after the onset of the energy application. Eight transient cases lasted 1 hour to 1 month (mean, 9.4 days; median, 7 days). Inadvertent atrioventricular block was related to the ablation anatomic site: 3 of 111 (2.7%) anteroseptal, 11 of 106 (10.4%) midseptal, and 2 of 197 (1.0%) right posteroseptal sites (P = .0007) for anteroseptal, P = .0001 for midseptal, and P = .17 for right posteroseptal versus nonright septal sites). Five of 314 (1.6%) ablations for atrioventricular nodal reentrant tachycardia resulted in atrioventricular block (P = .004 versus nonright septal sites). Compared with a matched subgroup, radiofrequency ablation experience was the only significant risk factor (32.7 versus 106.6, P = .002) for the occurrence of atrioventricular block. CONCLUSIONS Inadvertent atrioventricular block may occur during or late after radiofrequency catheter ablation. It is associated with ablations for (1) anterior and midseptal accessory pathways and atrioventricular nodal reentry and (2) relative institutional inexperience.

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).

Development of a pediatric cardiology quality improvement collaborative: From inception to implementation. From the joint council on congenital heart disease quality Improvement task force

While clinical outcomes in pediatric cardiac disease have improved in recent years, marked institutional and individual cardiology practice variability exists. Quality improvement science has demonstrated that reducing process variation leads to more favorable outcomes, safer practices, cost savings, and improved operating efficiency. This report describes the process undertaken to develop the first collaborative quality improvement project of the Joint Council on Congenital Heart Disease. The project chosen aims to reduce mortality and improve the quality of life of infants with hypoplastic left heart syndrome during the interstage period between discharge from the Norwood procedure and admission for the bidirectional Glenn procedure. The objective of this special article is to inform the pediatric cardiology and cardiac surgery communities of the project to help ensure that the early work by the project pilot participants will spread to clinicians caring for children with cardiovascular disease. It is anticipated that this project will add to our understanding of care for this challenging group of children with hypoplastic left heart syndrome, identifying clinical care changes with the potential to lead to improvements in outcome. It will also introduce the field of pediatric cardiology to the science of collaborative quality improvement and assist in reducing clinical process variation and improving patient outcomes across centers. Finally, it will establish an ongoing network of pediatric cardiologists and their teams linked through a longitudinal data set and collaboration for improvement and research.

The learning curve for radiofrequency ablation of tachyarrhythmias in pediatric patients

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.