Adenosine- and verapamil-sensitive ventricular tachycardia in the newborn.

Two neonates presented with sustained, monomorphic VT. Transesophageal electrophysiological studies demonstrated that the VTs were initiated with burst atrial pacing in one and noninducible in the other, and both terminated with burst atrial pacing and with adenosine. Oral verapamil suppressed the VTs in both. Following discontinuation of verapamil at 1 year of age, both children remain free of tachycardia recurrence at 3 and 4 years of age. These cases suggest that cAMP-mediated triggered activity may be responsible for some VTs in infancy.

Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia.

OBJECTIVE: This pharmacokinetic-pharmacodynamic study was designed to define the steady-state relationship between pharmacologic response and dose or concentration of sotalol in children with cardiac arrhythmias, with an emphasis on neonates and infants. METHODS: The treatment consisted of an upward titration with unit doses of 10, 30, and 70 mg of sotalol per square meter of body surface area. The patients received 3 doses at each dose level. The dosing interval was 8 hours. The Class III and beta-blocking activities of sotalol were derived from the QT and R-R intervals, respectively, of the surface electrocardiogram, which was recorded at 6 scheduled times before and after the third, sixth, and ninth doses. During these three dose intervals, 4 scheduled blood samples were also collected. Drug concentrations were measured with a validated nonstereoselective liquid chromatographic tandem mass spectrometric detection assay. Pharmacokinetic and pharmacodynamic parameters were obtained with standard methods. RESULTS: Twenty-one centers enrolled 25 patients in the study: 7 were neonates, 9 were infants, and 11 were children between the ages of 2 years and 12 years. The area under the drug concentration-time curve increased proportionately with dose. The apparent oral clearance of sotalol was linearly correlated with body surface area and creatinine clearance. The smallest children (body surface area <0.33 m2) displayed greater drug exposure than the larger children. The increase of QTc and R-R intervals was dose dependent. At the 70-mg/m(2) dose level, the mean (+/- standard deviation) maximum increase for the QTc interval was 14% +/- 7% and the average Class III effect during a dose interval was 7% +/- 5%. At the same dose level, the mean maximum increase of the R-R interval was 25% +/- 15% and the average beta-blocking effect during a dose interval was 12% +/- 13%. The effects tended to be larger in the smallest children. The Class III response and the plasma concentrations of sotalol were linearly related. The treatment was well tolerated. CONCLUSIONS: The steady-state pharmacokinetics of sotalol were dose proportionate. Pharmacologically important beta-blocking effects were observed at the 30-mg/m2 and 70-mg/m2 dose levels. Important Class III effects were seen at the 70-mg/m2 dose level. The Class III effect was linearly related to the drug concentration.

Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia.

The pharmacokinetics (PK) of the antiarrhythmic sotalol, which elicits Class III and beta-blocking activity, has not been adequately defined in a pediatric population with tachyarrhythmias. The goal of this single-dose study with administration of sotalol HCl at a dose level of 30 mg/m2 body surface area (BSA) was to define the PK of the drug in the following four age groups: neonates (0-30 days), infants (1 month to 2 years), younger children (> 2 to < 7 years), and older children (7-12 years) with tachyarrhythmias of either supraventricular or ventricular origin. The drug was administered in an extemporaneously compounded syrup formulation prepared from the tablets containing sotalol HCl. For safety, vital signs and adverse events were recorded and the QTc interval and heart rate telemetrically monitored. Scheduled blood samples were taken over a 36-hour time interval following dose administration. The drug concentrations in plasma were measured by a sensitive and specific LC/MS/MS assay. Standard compartment model-independent methods were applied to compute the salient PK parameters of sotalol. Twenty-four clinical sites enrolled 34 patients. Thirty-three had analyzable data. Sotalol was rapidly absorbed, with mean peak concentrations occurring 2 to 3 hours after administration. The elimination of sotalol was characterized by an average half-life of between 7.4 and 9.2 hours in the four age groups. There existed statistically significant linear relationships between apparent total clearance (CL/f) or apparent volume of distribution (V lambda z/f) after oral administration and the covariates BSA, creatinine clearance (CLcr), body weight (BW), or age. The best predictors for CL/f were CLcr and BSA, whereas BW best predicted the V lambda z/f. The total area under the drug concentration-time curve in the smallest children with a BSA < 0.33 m2 was significantly greater than that in the larger children. This finding indicated that the BSA-based dose adjustment used in this study led to a larger exposure in the smallest children, whereas the exposure to the drug was similar in the larger children. The dose of 30 mg/m2 was tolerated well. No serious drug-related adverse events were reported. It can be concluded that the PK of sotalol in the pediatric patients depended only on body size, except for the neonates and smallest infants in whom the disposition of sotalol was determined by both body size and maturation of eliminatory processes.

Mortality following radiofrequency catheter ablation (from the Pediatric Radiofrequency Ablation Registry). Participating members of the Pediatric Electrophysiology Society.

Deaths have been reported following radiofrequency catheter ablation (RFCA), but the mortality rate in children has not been defined. This study sought to analyze the incidence and the factors associated with mortality related to RFCA. Ten of 4,651 cases (0.22%) reported to the Pediatric RFCA Registry resulting in death were reviewed and compared with a matched control group (n = 18). Death occurred in 5 of 4,092 children (0.12%, ages 0.1 to 13.3 years) with structurally normal hearts. Death was related to traumatic injury, myocardial perforation and hemopericardium, coronary or cerebral thromboembolism, and ventricular arrhythmia. All cases were left-sided (p = 0.019 vs right or septal) supraventricular arrhythmias with radiofrequency applications in the systemic atrium and/or ventricle, and all procedures were successful. Mortality occurred in 5 of 559 children (0.89%, p = 0.001 vs normals, ages 1.5 to 17.4 years) with structural heart disease. No new pathology except the mural radiofrequency lesions was seen at autopsy. Those with structurally normal hearts who died were smaller (32.7 vs 55.6 kg, p = 0.023) and had more radiofrequency applications (26.3 vs 8.7, p = 0.019) than those who survived. No differences were demonstrated for those with abnormal hearts. Operator experience was not different (deaths 103 +/- 106 vs controls 117 +/- 125, p = 0.41). Mortality associated with pediatric RFCA is rare, but is more frequent when there is underlying heart disease, lower patient weight, greater number of radiofrequency energy applications, and left-sided procedures. Operator experience does not appear to be a factor leading to mortality.

An assessment of desflurane for use during cardiac electrophysiological study and radiofrequency ablation of supraventricular dysrhythmias in children.

Desflurane has several properties making it a desirable agent for use in electrophysiological studies (EPS) for diagnosis and treatment of cardiac dysrhythmias. We studied 47 children, mean age 12.8+/-4.6 years, mean weight 52.9+/-24.0 kg, with clinical history of supra- ventricular tachycardia (SVT) during EPS using desflurane in a crossover comparison with fentanyl. The patients served as their own controls. All received oral premedication with lorazepam, and intravenous induction with thiopentone, rocuronium, and oxygen. Group 1 (n=24) were administered fentanyl 10 microg.kg-1 bolus i.v. with an infusion of 3 microg.kg-1.h-1 during initial EPS. Fentanyl was discontinued and desflurane, 6% endtidal, was administered and the EPS repeated. Group 2 (n=23) were initially administered 6% desflurane after induction, and following EPS the desflurane was discontinued and the patients administered fentanyl 3 microg.kg-1 bolus and EPS repeated (explanations of EPS abbreviations are provided). Desflurane reduced the mean arterial pressure (MAP) in all patients. In Group 1, desflurane shortened the sinus cycle length (SCL), i.e. increasing the heart rate, and atrial effective refractory period (AERP) while Group 2 demonstrated no such effect on AERP. There were no other significant differences between fentanyl or desflurane techniques in terms of EPS measurements. SVT was inducible with both agents in both groups. Desflurane seems an acceptable agent for use during EPS procedures.

Spontaneous resolution of atrioventricular dissociation in utero.

Fetal atrioventricular dissociation is a dysrhythmia associated with significant antenatal and postnatal morbidity and mortality. We present a case of a 19-week-old fetus with atrioventricular dissociation, which spontaneously resolved. The mother had no signs of autoimmune disease. The fetus had an uneventful gestation and, after delivery, had a normal cardiac and transesophageal electrophysiological evaluation.

Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary vasculature in children with pulmonary hypertension.

We sought to describe the morphologic characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in children with and without pulmonary hypertension to compare these anatomic findings with those of pulmonary wedge angiography, and to determine the relation between these structural findings and functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary vascular structure in children with pulmonary hypertension with current imaging techniques has been limited and little is known about the relation between structural and functional characteristics of the pulmonary vasculature. In 23 children undergoing cardiac catheterization (15 with pulmonary hypertension and 8 controls) we performed IVUS and pulmonary wedge angiography of the distal pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15 children with pulmonary hypertension. Baseline pulmonary vascular resistance (PVR) was greater in the 15 children with pulmonary hypertension than in the 8 controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary hypertension showed a thicker middle layer, wall thickness ratio, and diminished pulsatility than did those in controls (p <0.05). The inner layer was not visualized by IVUS in any control patient, but was seen in 9 of 15 patients with pulmonary hypertension. Pulmonary artery wedge angiography correlated with baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of wall thickness ratio and inner layer thickness. The inner layer was not visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity to NO and oxygen did not correlate with structural assessment of the pulmonary vasculature by IVUS. Structural changes in the pulmonary arteries in children with pulmonary hypertension can be directly visualized by IVUS, but are not predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary arteries may complement current techniques utilized in the evaluation of children with pulmonary hypertension.

Inadvertent atrioventricular block during radiofrequency catheter ablation. Results of the Pediatric Radiofrequency Ablation Registry. Pediatric Electrophysiology Society.

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.

Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope.

Overall, these results indicate that oral treatment of neurally mediated syncope is safe and efficacious. Further randomized trials in children will be required to determine the significance of a placebo effect, as well as potential differences in results related to the mechanism of syncope.

Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity.

To determine whether circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, are elevated in children with pulmonary hypertension and related to the degree of hypoxic pulmonary vasoconstriction, we measured arterial and mixed venous plasma concentrations of immunoreactive ET-1 (irET-1) in 13 children during cardiac catheterization. Clinical diagnoses in seven children with pulmonary hypertension (PH) included chronic lung disease (four children), congenital heart disease after surgical repair (two children), and primary ("reactive") pulmonary hypertension (one child). Blood samples were simultaneously obtained from pulmonary artery (venous) and systemic arterial sites during baseline conditions. Plasma irET-1 was elevated in children with PH (12.3 +/- 3.4 versus 3.6 +/- 0.7 pg/ml, PH versus non-PH; p < 0.01). Arterial/venous irET-1 ratios in the PH group (1.1 +/- 0.2) were not different from those in the non-PH group. During acute hypoxia, mean Ppa increased from 27 +/- 3 to 40 +/- 5 mm Hg. Basal irET-1 correlated strongly with the degree of elevation of mean Ppa during acute hypoxia (r = 0.69; p < 0.02). We conclude that irET-1 levels are often elevated in children with PH, and they are strongly correlated with pulmonary vasoreactivity during acute hypoxia. Whether elevated irET-1 levels contribute directly to or are markers of altered pulmonary vascular tone and reactivity in children with PH remains speculative.

Radiofrequency catheter ablation of an accessory atrioventricular connection in a Fontan patient.

Radiofrequency catheter ablation is fast becoming the procedure of choice for the nonpharmacological treatment of atrioventricular connections that are responsible for debilitating tachycardias. We, herein, present a case of reentrant supraventricular tachycardia secondary to an atrioventricular connection in a Fontan patient that was successfully treated with radiofrequency catheter ablation.

Ventriculoatrial intervals during narrow complex reentrant tachycardia in children.

Ventriculoatrial (VA) intervals during narrow complex tachycardia were measured in a pediatric population. The VA intervals were similar to those in adults but were slightly shorter. In the pediatric subjects values less than 60 msec excluded the participation of an accessory pathway in the tachycardia circuit. Three out of 11 patients with atrioventricular nodal reentrant tachycardia (AVNRT) had VA values greater than or equal to 70 msec, while 5 of 28 patients with orthodromic reciprocating tachycardia (ORT) had values less than or equal to 70 msec. Using a cut-off value of 70 msec as the sole criteria to distinguish between ORT and AVNRT could lead to errors in classification of the underlying mechanism of the tachycardia.

The longitudinal time course of QTc in early infancy. Preliminary results of a prospective sudden infant death syndrome surveillance program.

Eleven hundred one healthy neonates in Charleston County, SC, were enrolled in a prospective, serial measurement sudden infant death syndrome/QT surveillance program. Automated computer-enhanced ECGs were recorded at 1 day of age in the hospital nursery and again at 1 week and 1, 2, and 3 months in the participant's home. At 1 year, the families were contacted by phone or mail and questioned as to the health of the child. Validation studies demonstrated the computer-enhanced ECGs to be 96% accurate, whereas traditional ECG recording and measurement was 94% accurate. No systematic differences in the QTc according to race and sex were observed. There were parallel longitudinal time courses for each race and sex group with a significant (P less than .001) shortening of the QTc at 1 week. There was no evidence of tracking of the QTc during the first 3 months of life. In conclusion, (1) automated, enhanced ECG QTc intervals are superior to traditional electrocardiography while retaining the advantages of automation; (2) there is a significant shortening of the QTc during the first month of life; and (3) a home follow-up sudden infant death syndrome surveillance program is feasible and produces accurate, reliable information.

Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing greater than or equal to 1,200 meters above sea level.

Little data are available on the hemodynamic effects of premedications and anesthetic agents on infants and children. Ketamine is the most frequently used anesthetic agent for cardiac catheterization procedures in pediatric patients with congenital heart disease. Previous reports both suggest and deny ketamine's pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive equipment, one of the few indications for cardiac catheterization is to obtain accurate pressure data. If ketamine alters pulmonary vascular resistance, it would negate the primary reason for the procedure. Because the patient population studied herein resides greater than or equal to 1,200 meters above sea level, concerns about pharmacologic effects on pulmonary vascular resistance are enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution cardiac outputs, and blood gases were measured in room air (16% oxygen) and with ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia identified 3 groups: normal, intermediate and hyperresponders. The normal responders had normal resistance ratios (0.11) in room air and had little resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine (+0.01). The intermediate responders had a slightly higher but normal resistance ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (-0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17) and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance ratio than hypoxia alone in patients with reactive pulmonary vascular beds. Ketamine should not be used in children undergoing procedures to establish operability based on pulmonary vascular resistance or pulmonary vascular reactivity.

Late sudden unexpected deaths in hospitalized infants with bronchopulmonary dysplasia.

To determine the relative contribution of sudden death as a cause of late inpatient mortality in newborns after prolonged mechanical ventilation, we reviewed the charts of 348 patients who received ventilation assistance and who were admitted to the neonatal intensive care unit during a 26-month period. The overall mortality rate for these patients was 25%, with 88% (77/88) of these deaths occurring within 30 days of birth. Eleven infants died after more than 60 days of mechanical ventilation. Seven of these late deaths were sudden, unexpected in-hospital deaths. Sudden deaths occurred at a mean (uncorrected) age of 12 months (range, 4 to 27 months), during periods when infants appeared to be stable or clinically improving, were unrelated to recent respiratory exacerbations, and occurred despite prompt resuscitative efforts. Four infants still required mechanical ventilation, and 4 had tracheostomies at the time of death. All of the infants had chronic hypercarbia (greater than 50 mm Hg) and an elevated serum bicarbonate level (greater than 30 mmol/L), but not hyponatremia, hypochloremia (less than 80 mmol/L), or alkalemia. Left and right ventricular hypertrophy, multiple drug therapy, recurrent cyanotic episodes, and frequent unexplained fevers were common. In comparison with 17 bronchopulmonary dysplasia survivors who required longer than 60 days of ventilation therapy, the late deaths group more frequently had left ventricular hypertrophy and received prolonged combination theophylline anhydrous and beta-adrenergic agonist therapy. We report that sudden death can occur in infants with severe bronchopulmonary dysplasia despite in-hospital cardiopulmonary monitoring and the rapid institution of cardiopulmonary resuscitation, and is a significant cause of late mortality in infants who receive ventilation therapy for longer than 2 months.

Pulmonary vascular extraction of circulating norepinephrine in infants with bronchopulmonary dysplasia.

Although the pulmonary circulation in infants with advanced bronchopulmonary dysplasia (BPD) is characterized by abnormal structure and vasoreactivity, metabolic lung functions have not been studied in these infants. To test the hypothesis that patients with severe BPD may have abnormal metabolic lung function, we assessed the pulmonary vascular extraction of circulating norepinephrine in six children with BPD during cardiac catheterization. Plasma norepinephrine levels were measured from simultaneously drawn mixed venous (main pulmonary artery) and left atrium or femoral artery samples. In comparison with four infants with mild heart disease without pulmonary hypertension, we found that infants with BPD extract proportionately less norepinephrine than non-BPD infants [-7 +/- 50% (BPD) versus +27 +/- 6% (non-BPD); P less than 0.001, t test]. Three infants with BPD had higher arterial than mixed venous concentrations of plasma norepinephrine, suggesting net production across the lung. Plasma catecholamine levels and percent extraction correlated poorly with cardiac index and systemic and pulmonary vascular resistance indices. However, this study group was characterized by a high incidence of pulmonary (6/6) and systemic (4/6) hypertension, left ventricular hypertrophy (4/6), and subsequent death (3/6). We conclude that infants with severe BPD and pulmonary hypertension have decreased pulmonary vascular clearance or net production of circulating norepinephrine, but links between altered pulmonary catecholamine metabolism and pulmonary hypertension, or other cardiovascular abnormalities associated with BPD, remain speculative.

The St. Jude Medical cardiac valve in infants and children: role of anticoagulant therapy.

The experience at the University of Colorado with the St. Jude Medical cardiac valve was reviewed to determine the feasibility of placing this prosthesis in children and the role of anticoagulation. A St. Jude Medical cardiac valve was placed in 33 patients ranging in age from 2.5 months to 17 years. Seven patients were less than 1 year of age. Nineteen valves were placed in the aortic position in patients aged 5 months to 17 years (mean 9.5 years). Five patients had valve replacement only, 13 had concomitant aortoventriculoplasty and 1 a Manouguian procedure. Indications for anulus enlarging procedures were recurrent subaortic stenosis or inability to place an adult-sized valve in the native aortic anulus, or both. There were no early or late deaths. Fourteen valves were placed in the mitral position. They were anular positioned in 6 patients aged 6 months to 16 years and supraanular positioned in 8 patients aged 2.5 months to 2 years. There were no deaths with the anular positioned replacements and seven deaths (two early and five late) with the supraanular positioned replacements. Four of the five late deaths were associated with marked pre- and postoperative left ventricular dysfunction. The follow-up time was 784 patient-months in 31 long-term survivors. Anticoagulation was achieved with warfarin, usually in combination with sulfinpyrazone, dipyridamole or aspirin. There were four episodes of thromboembolism, three occurring in patients with suboptimal anticoagulation, and one in a patient lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise radionuclide right ventriculography in children.

Supine exercise equilibrium radionuclide right ventriculography was performed in 13 children (8-18 years) with hypercholesterolemia. Phase analysis was used to construct right ventricular regions of interest, and a peri-right ventricular region was used for background correction. Right ventricular ejection fraction at rest and exercise was 50.5 +/- 9.2% and 61.5 +/- 8.1%, respectively, with a mean increase of 11.0 +/- 7.5 percentage units (range 1-27 percentage units). During exercise, end-diastolic volume remained unchanged while end-systolic volume decreased by 19.4%, producing a 21.7% increase in stroke volume. Stroke volume ratios (left ventricular stroke volume counts/right ventricular stroke volume counts) approach unity (1.00 +/- 0.27). However, interobserver and intraobserver correlations are just fair, implying only a modest degree of accuracy and reliability of the procedure. This imprecision needs to be considered when evaluating the results of nuclear equilibrium right ventriculography.