Effects of beta-adrenergic antagonists on the QT measurements from exercise stress tests in pediatric patients with long QT syndrome.

It has been proposed that beta-adrenergic antagonist protection against cardiac events in patients with long QT syndrome (LQTS) may be related to a decrease in baseline QTc dispersion. To determine the effects of beta-blocker therapy on QT measurements, we evaluated the exercise tests of 25 pediatric patients with LQTS. Measurements were made of the maximum QTc interval and QTc dispersion during the various segments of the exercise test. There was no statistically significant difference between the pre-beta-blocker and post-beta-blocker maximum QTc interval during the supine (0.473 +/- 0.039 vs 0.470 +/- 0.038 sec), exercise (0.488 +/- 0.044 vs 0.500 +/- 0.026 sec), or recovery (0.490 +/- 0.031 vs 0.493 +/- 0.029 sec) phases of the exercise stress test. There was also no statistically significant difference between the pre-beta-blocker and post-beta-blocker QTc dispersion during the supine (0.047 +/- 0.021 vs 0.058 +/- 0.033 exercise vs 0.063 +/- 0.028 sec), or recovery (0.045 +/- 0.023 vs 0.052 +/- 0.026 sec) phases of the exercise stress test. Therefore, the protection that beta-blockers offer appears not to be related to a reduction of the baseline QTc interval or a decrease of QTc dispersion.

Evaluation and treatment of syncope in infants.

Syncope in the infant and newborn occurs as a loss of consciousness due to a variety of etiologies. Because syncope at this age may be a harbinger of sudden infant death, the symptom provokes anxiety and challenges clinicians to identify those babies with an increased risk for life threatening events. Recently introduced diagnostic tests and advances in molecular biology offer promising potential, but the population at risk remains unknown. Controversy surrounds: many potential risk factors; the value of home monitoring; and appropriate preventive and therapeutic strategies. This article reviews the differential diagnosis of syncope in children less than 18 months of age, with particular attention to those diagnoses and problems specific to the evaluation and treatment in this age group. Recommendations are presented for an efficient evaluation, which must include a careful history, complete physical examination and thorough investigation of the family history and home environment. In addition, specific diagnostic tests and a practical approach to treatment are suggested.

Permanent epicardial pacing in pediatric patients: seventeen years of experience and 1200 outpatient visits.

BACKGROUND: The purpose of this study was to evaluate the long-term outcome of all pediatric epicardial pacing leads. METHODS AND RESULTS: All epicardial leads and 1239 outpatient visits between January 1, 1983, and June 30, 2000, were retrospectively reviewed. Pacing and sensing thresholds were reviewed at implant, at 1 month, and at subsequent 6-month intervals. Lead failure was defined as the need for replacement or abandonment due to pacing or sensing problems, lead fracture, or phrenic/muscle stimulation. A total of 123 patients underwent 207 epicardial lead (60 atrial/147 ventricular, 40% steroid) implantations (median age at implant was 4.1 years [range 1 day to 21 years]). Congenital heart disease was present in 103 (84%) of the patients. Epicardial leads were followed for 29 months (range 1 to 207 months). The 1-, 2-, and 5-year lead survival was 96%, 90%, and 74%, respectively. Compared with conventional epicardial leads, both atrial and ventricular steroid leads had better stimulation thresholds 1 month after implantation; however, only ventricular steroid leads had improved chronic pacing thresholds (at 2 years: for steroid leads, 1.9 muJ [from 0.26 to 16 mu]; for nonsteroid leads, 4.7 muJ [from 0.6 to 25 muJ]; P<0.01). Ventricular sensing was significantly better in steroid leads 1 month after lead implantation (at 2 years: for steroid leads, 8 mV [from 4 to 31 mV]; for nonsteroid leads, 4 mV [from 0.7 to 10 mV]; P<0.01). Neither congenital heart disease, lead implantation with a concomitant cardiac operation, age or weight at implantation, nor the chamber paced was predictive of lead failure. CONCLUSIONS: Steroid epicardial leads demonstrated relatively stable acute and chronic pacing and sensing thresholds. In this evaluation of >200 epicardial leads, lead survival was good, with steroid-eluting leads demonstrating results similar to those found with historical conventional endocardial leads.

Epicardial pacemaker implantation and follow-up in patients with a single ventricle after the Fontan operation.

OBJECTIVES: There is an increasing incidence of sinus node dysfunction after the Fontan procedure. Inability to maintain atrioventricular synchrony after the Fontan operation has been associated with an adverse late outcome. Although pacing may be helpful as a primary or adjunct modality after the Fontan procedure, the effects of performing a late thoracotomy or sternotomy for epicardial pacemaker implantation are unknown. In addition, little is known about the long-term effectiveness of epicardial leads in patients with single ventricles. The purpose of this study was to compare the hospital course and follow-up of epicardial pacing lead implantation in patients with Fontan physiology and patients with 2-ventricle physiology. METHODS: We retrospectively reviewed all isolated epicardial pacemaker implantations and outpatient evaluations performed between January 1983 and June 2000. RESULTS: There was no difference in the perioperative course for the 31 Fontan patients (27 atrial and 41 ventricular leads [68 total]) compared with the 56 non-Fontan subjects (9 atrial and 61 ventricular leads [70 total]). The median length of stay in Fontan and non-Fontan patients was 3 and 4 days, respectively. There was no early mortality in either group. Pleural drainage for 5 days or longer was reported in 4% of the Fontan cohort and 3% of the non-Fontan group. Late pleural effusions were identified in only 2 patients in the Fontan group and 2 patients in the non-Fontan group. There was no significant difference in epicardial lead survival between the Fontan group and the non-Fontan group (1 year, 96%; 2 years, 90%; 5 years, 70%). The overall incidence of lead failure was 17% (24/138). CONCLUSIONS: Epicardial leads can be safely placed in Fontan patients at no additional risk compared to patients with biventricular physiology. Sensing and pacing qualities were relatively constant in both the Fontan and non-Fontan groups over the first 2 years after implantation.

Fetal and neonatal arrhythmias.

Perinatal arrhythmias may occur either during fetal life or in the early neonatal period. These arrhythmias include both tachycardias and bradycardias. This article presents a brief overview of fetal and neonatal arrhythmias concentrating on their presentation, diagnosis, and treatment.

Creation of viable pulmonary artery autografts through tissue engineering.

BACKGROUND: "Repair" of many congenital cardiac defects requires the use of conduits to establish right ventricle to pulmonary artery continuity. At present, available homografts or prosthetic conduits lack growth potential and can become obstructed by tissue ingrowth or calcification leading to the need for multiple conduit replacements. Tissue engineering is an approach by which cells are grown in vitro onto biodegradable polymers to construct "tissues" for implantation. A tissue engineering approach has recently been used to construct living cardiac valve leaflets from autologous cells in our laboratory. This study assesses the feasibility of a tissue engineering approach to constructing tissue-engineered "living" pulmonary artery conduits. MATERIALS AND METHODS: Ovine artery (group A, n = 4) or vein (group V, n = 3) segments were harvested, separated into individual cells, expanded in tissue culture, and seeded onto synthetic biodegradable (polyglactin/polyglycolic acid) tubular scaffolds (20 mm long x 15 mm diameter). After 7 days of in vitro culture, the autologous cell/polymer vascular constructs were used to replace a 2 cm segment of pulmonary artery in lambs (age 68.4 +/- 15.5 days, weight 18.7 +/- 2.0 kg). One other control animal received an acellular polymer tube sealed with fibrin glue without autologous cells. Animals were sacrificed at intervals of 11 to 24 weeks (mean follow-up 130.3 +/- 30.8 days, mean weight 38.9 +/- 13.0 kg) after echocardiographic and angiographic studies. Explanted tissue-engineered conduits were assayed for collagen (4-hydroxyproline) and calcium content, and a tissue deoxyribonucleic acid assay (bis-benzimide dye) was used to estimate number of cell nuclei as an index of tissue maturity. RESULTS: The acellular control graft developed progressive obstruction and thrombosis. All seven tissue-engineered grafts were patent and demonstrated a nonaneurysmal increase in diameter (group A = 18.3 +/- 1.3 mm = 95.3% of native pulmonary artery; group V = 17.1 +/- 1.2 mm = 86.8% of native pulmonary artery). Histologically, none of the biodegradable polymer scaffold remained in any tissue-engineered graft by 11 weeks. Collagen content in tissue-engineered grafts was 73.9% +/- 8.0% of adjacent native pulmonary artery. Histologically, elastic fibers were present in the media layer of tissue-engineered vessel wall and endothelial specific factor VIII was identified on the luminal surface. Deoxyribonucleic acid assay showed a progressive decrease in numbers of cell nuclei over 11 and 24 weeks, suggesting an ongoing tissue remodeling. Calcium content of tissue-engineered grafts was elevated (group A = 7.95 +/- 5.09; group V = 13.2 +/- 5.48; native pulmonary artery = 1.2 +/- 0.8 mg/gm dry weight), but no macroscopic calcification was found. CONCLUSIONS: Living vascular grafts engineered from autologous cells and biodegradable polymers functioned well in the pulmonary circulation as a pulmonary artery replacement. They demonstrated an increase in diameter suggesting growth and development of endothelial lining and extracellular matrix, including collagen and elastic fibers. This tissue-engineering approach may ultimately allow the development of viable autologous vascular grafts for clinical use.

Tissue-engineered heart valve leaflets: does cell origin affect outcome?

BACKGROUND: We previously reported the successful creation of tissue-engineered valve leaflet constructs and the implantation of these autologous tissue leaflets in the pulmonary valve position in a lamb model. The optimal cell origin for creating these valve leaflets remains unclear. This study was designed to compare dermal with arterial wall myofibroblasts as the cells of origin for the leaflet constructs. METHODS AND RESULTS: Mixed cell populations of endothelial cells and fibroblasts were isolated from ovine femoral arteries or subdermis and then expanded in vitro. A synthetic biodegradable polymer scaffold was then seeded with the cultured cells. The tissue scaffold was composed of a polyglactin woven mesh sandwiched between two nonwoven polyglycolic acid mesh sheets, which measured 3x3 cm in size and 3.2 mm in thickness. The cell-seeded polymer construct was implanted to replace one pulmonary valve leaflet in the same juvenile animal from which the cells had originally been obtained. Using cardiopulmonary bypass, the right posterior leaflet of the pulmonary valve was completely resected and replaced with an autologous engineered valve leaflet. In group D (n=5), the cells were obtained from subdermis, and in group A (n=4), they were obtained from the arterial wall. Eight to 10 weeks after leaflet implantation, the animals were killed, and the implanted valve leaflets were examined histologically, biochemically, and biomechanically. The dimensions of each tissue-engineered leaflet (TEL) were compared with those of the two remaining native valve leaflets to obtain a growth index. A 4-hydroxyproline assay was performed to evaluate collagen content. Leaflet tensile strength was evaluated in vitro by using a Vitrodyne V-1000 mechanical tester. Factor VIII and elastin stains were performed to histologically assess the presence of endothelial cells and elastin, respectively. In all animals, the TEL persisted in the pulmonary valve position after 8 to 10 weeks, and all polyglycolic acid polymer had been degraded. Group A leaflets had a higher growth index (0.86+/-0.11) than group D (0.41+/-0.08) (P<.05). Macroscopically, the group D leaflets appeared thicker and contracted. Histologically, elastic fibers were more abundant in group A than in group D. Total collagen content and biomechanical testing showed no differences between groups. Leaflets from both groups had positive staining for factor VIII on the surface, confirming growth of endothelial cells to cover the TEL. CONCLUSIONS: Autologous TEL derived from vascular fibroblasts seem to develop functionally and morphologically like the native valve leaflets in the pulmonary circulation. Use of arterial myofibroblasts for the creation of TEL seems preferable to dermal fibroblasts with current tissue culture conditions.

High-rate atrial pacing as an innovative bridging therapy in a neonate with congenital long QT syndrome.

INTRODUCTION: The neonatal presentation of the long QT syndrome is rare, although it is frequently accompanied by life-threatening arrhythmias. Infants may not survive childhood despite traditional management with beta-adrenergic blockade and pacing. METHODS AND RESULTS: This case describes a newborn with a long QT interval, T wave alternans, intermittent 2:1 AV block, ventricular arrhythmias, and a family history of sudden death. After failing medical therapy, conventional VVI and DDD pacing were unsuccessful due to prolonged ventricular refractoriness and proarrhythmia. At 2 months of life, the child was treated with high-rate (180 ppm) atrial pacing to produce intentional 2:1 AV block. Following an episode of possible syncope at 16 months of age, an automatic implantable cardioverter defibrillator (ICD) was added. Finally, as recently reported, acutely induced hyperkalemia led to both a marked decrease in QTc and functional improvement in repolarization (consistent 1:1 AV conduction at rates to 180 beats/min). Spironolactone and dietary potassium were added and have produced the same effects chronically. CONCLUSIONS: High-rate atrial pacing with 2:1 AV block is presented as a novel and "bridging" therapy for neonatal long QT syndrome and 2:1 AV block with ventricular arrhythmias. Definitive therapy with ICD implantation was then possible when patient size was substantially increased. The electrophysiologic response to intentional elevation of the serum potassium suggests a genetic defect in an inward potassium channel and demonstrates a possible therapy of long QT syndrome in some future patients.

Syncope in the pediatric patient.

Syncope in the pediatric patient is a common and usually benign event that frequently causes concern and anxiety. This article describes three general categories of syncope in children and adolescents: cardiac, noncardiac, and neurocardiogenic. The discussion includes specific pediatric issues and dissimilarities when compared to adult patients with syncope. In addition, a focused approach to the diagnostic evaluation of syncope in childhood is described.

Five-year experience with radiofrequency catheter ablation: implications for management of arrhythmias in pediatric and young adult patients.

OBJECTIVE: A review of the results of the first 5 years of radiofrequency catheter ablation procedures performed at Children's Hospital, Boston, a large tertiary referral center for patients with congenital heart disease and arrhythmias common to the infant, child, and young adult. STUDY DESIGN: A retrospective review of 410 consecutive procedures in 346 patients who underwent at least one application of radiofrequency energy for the treatment of recurrent supraventricular or ventricular tachycardia. RESULTS: The overall final success rate for all diagnoses was 90%, with a higher success rate in patients with an accessory pathway (96%). During the 5-year study period, the success rate improved while the rates of failures and late recurrences declined. The incidence of serious complications was 1.2% (1 late death, 1 ventricular dysfunction, 1 complete heart block, 1 cardiac perforation, and 1 cerebrovascular accident). CONCLUSIONS: This report of a large series of radiofrequency catheter ablation procedures performed at an institution committed to treating congenital heart disease and pediatric arrhythmias confirms the safety and efficacy of this procedure. The pediatric cardiologist/electrophysiologist treating such patients must be aware of specific technical, anatomic, and electrophysiologic variations in the pediatric patient that are critical to the success of this therapy.

Prospective comparison of culture vs genome detection for diagnosis of enteroviral meningitis in childhood.

OBJECTIVE: To assess the sensitivity and specificity of a new polymerase chain reaction (PCR) assay with uninterrupted reverse transcription and complementary DNA amplification (RT-PCR) for the diagnosis of enteroviral (EV) meningitis in children. DESIGN: A prospective, cohort study. SETTINGS: Two medical centers: 1 university hospital and 1 children's hospital in San Diego County, California, during a 5-week period. PATIENTS: All pediatric patients younger than 16 years who underwent a lumbar puncture for evaluation of possible meningitis. MAIN OUTCOME MEASURES: The results of cerebrospinal fluid (CSF) RT-PCR were compared with viral cultures and clinical histories. RESULTS: During the 5-week period, 90 patients were entered into the study. Nonpolio EVs were cultured from 10% (9/90) of the patients from the following sites: CSF, 6.7% (6/90) of the patients; stool, 19% (4/21) of the patients; and throat swabs, 5.6% (1/18) of the patients. The EV genome was detected in the CSF by using RT-PCR in 7 of 9 EV culture-positive patients. The sensitivity and specificity of the CSF RT-PCR assay to detect EV meningitis were 77.8% and 100%, respectively. This compared with a sensitivity of 66.7% for detection of EV in CSF by viral culture alone. CONCLUSION: The new RT-PCR assay is a rapid and reliable method for the detection of EV infection in childhood.

Tissue engineering lamb heart valve leaflets.

Tissue engineered lamb heart valve leaflets (N - 3) were constructed by repeatedly seeding a concentrated suspension of autologous myofibroblasts onto a biodegradable synthetic polymeric scaffold composed of fibers made from polyglycolic acid and polylactic acid. Over a 2-week period the cells attached to the polymer fibers, multiplied, and formed a tissue core in the shape of the matrix. The tissue core was seeded with autologous large-vessel endothelial cells that formed a monolayer which coated the outer surface of the leaflet. The tissue engineered leaflets were surgically implanted in place of the right posterior pulmonary valve leaflet of the donor lamb while on cardiopulmonary bypass. Pulmonary valve function was evaluated by two-dimensional echocardiography with color Doppler which demonstrated valve function without evidence of stenosis and with only trivial regurgitation under normal physiologic conditions. Histologically, the tissue engineered heart valve leaflets resembled native valve leaflet tissue.

Tissue engineering heart valves: valve leaflet replacement study in a lamb model.

BACKGROUND: Valve replacements using either bioprosthetic or mechanical valves have the disadvantage that these structures are unable to grow, repair, or remodel and are both thrombogenic and susceptible to infection. These characteristics have significantly limited their durability and longevity. In an attempt to begin to overcome these shortcomings, we have tested the feasibility of constructing heart valve leaflets in lambs by seeding a synthetic polyglycolic acid fiber matrix in vitro with fibroblasts and endothelial cells. METHODS: Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low-density lipoprotein marker and separated from the fibroblasts using a fluorescent activated cell sorter. A synthetic biodegradable scaffold constructed from polyglycolic acid fibers was seeded with fibroblasts, which grew to form a tissue-like sheet. This tissue was subsequently seeded with endothelial cells, which formed a cellular monolayer coating around the leaflet. Using these constructs, autologous (n = 3) and allogenic (n = 4) tissue engineered leaflets were implanted in 7 animals. In each animal the right posterior leaflet of the pulmonary valve was resected and replaced with an engineered valve leaflet. RESULTS: All animals survived the procedure. Postoperative echocardiography demonstrated no evidence of stenosis and trivial pulmonary regurgitation in the autografts and moderate regurgitation in the allogenic valves. Collagen analysis of the constructs showed development of an extracellular matrix. Histologic evaluation of the constructs demonstrated appropriate cellular architecture. CONCLUSIONS: This preliminary experiment showed that a tissue engineered valve leaflet constructed from its cellular components can function in the pulmonary valve position. Tissue engineering of a heart valve leaflet is feasible, and these preliminary studies suggest that autograft tissue will probably be superior to allogenic tissue.

Sotalol for refractory arrhythmias in pediatric and young adult patients: initial efficacy and long-term outcome.

Sotalol is an antiarrhythmic medication that has properties of both a beta-blocker and a class III agent and has been used safely and effectively to treat arrhythmias of multiple mechanisms in pediatric patients. The purpose of this study was to review our institutional experience with sotalol in 45 patients with refractory arrhythmias and determine their long-term outcome. Patients responded to sotalol with 80% efficacy and a 22% incidence of adverse side effects. The mean sotalol dose was 116 mg/m2/day, and the average duration of therapy was 15.2 months. In spite of 80% efficacy, only 22% of patients remained on sotalol long-term. Sotalol was discontinued most commonly for either spontaneous resolution of disease or definitive cure by radiofrequency ablation. Other reasons for discontinuation of effective therapy included adverse side effects and arrhythmia control with either an antitachycardia pacemaker or another medication. One patient died while taking sotalol, but this case was considered a failure of treatment rather than an adverse side effect. Of the patients who still receive therapy, several have complex structural heart disease and require a combination of therapies, including sotalol, for adequate rhythm control.

Coronary artery abnormalities detected at cardiac catheterization following the arterial switch operation for transposition of the great arteries.

Because the arterial switch operation has become the routine surgical approach for transposition of the great arteries, there is increasing awareness of adverse sequelae in some survivors. For the arterial switch to be considered the procedure of choice for transposition of the great arteries, long-term patency and normal function of the translocated coronary arteries must be achieved. We reviewed the cineangiograms and hemodynamic data in 366 patients who underwent postoperative catheterization after arterial switch operation. Of these, 13 patients (3%) had previously unsuspected coronary abnormalities diagnosed angiographically. No patient had noninvasive evidence of resting systolic dysfunction. Findings included left main coronary artery stenosis (n = 3) or occlusion (n = 2), anterior descending coronary artery stenosis (n = 1) or occlusion (n = 2), right coronary artery stenosis (n = 1) or occlusion (n = 1), and small coronary artery fistulas (n = 3). One patient died suddenly 3.3 years after surgery, 1 patient is lost to follow-up, and the remaining 10 patients are alive and asymptomatic up to 11 years after surgery.