Costs and utility of tests in the evaluation of the pediatric patients with syncope.

New diagnostic tests have markedly improved the ability to establish a cause of syncope in pediatric patients, but at a substantial cost. The goal of syncope evaluation should be to diagnose treatable causes and identify patients at high risk for sudden death. The diagnostic utility of commonly used tests is reviewed. Although there are limited data on the application of specific diagnostic tests in the child with syncope, most tests have a low yield in unselected patients. A more directed approach to testing, based on the results of history, physical examination and the electrocardiogram is likely to result in significant cost reduction while still identifying patients with life threatening disorders. Validation of such an approach awaits prospective evaluation.

Late occurrence of heart block after radiofrequency catheter ablation of the septal region: clinical follow-up and outcome.

INTRODUCTION: There are few data regarding the occurrence of delayed heart block at least 24 hours after radiofrequency catheter ablation (RFCA) of AV nodal reentry or posteroseptal accessory pathways (APs). We investigated the late occurrence of heart block in this population, the clinical outcome, and whether findings at electrophysiologic study could have predicted its development. METHODS AND RESULTS: Two of 418 patients with AV nodal reentry undergoing RFCA using a posterior approach and 1 of 54 patients with RFCA of a posteroseptal AP developed late heart block. Anterograde and retrograde AV nodal conduction before and after RFCA were normal. Patients received 12, 15, and 32 RFCA lesions, respectively, using a mean maximum power of 44 W. The RFCA sites were the posterior septum for posteroseptal AP and the posterior and mid-septum for patients with AV nodal reentry, with no His electrogram ever recorded at the ablation site. During RFCA, junctional tachycardia occurred with 1:1 VA conduction in the patient with a posteroseptal AP, but occasional intermittent single retrograde blocked complexes were present in both patients with AV nodal reentry. No rapid junctional tachycardia or >1 consecutive retrograde blocked complex was ever observed during RFCA. Persistent high-degree AV block with junctional escape developed 2 days after RFCA in the posteroseptal AP patient. A permanent pacemaker was implanted, and normal conduction was noted 16 days after RFCA. Both patients with AV nodal reentry complained of fatigue, mainly on exertion, 3 to 4 days after RFCA, and ECG-documented exercise-induced variable AV block was obtained. Because heart block resolved in our initial patient, a prolonged monitoring period was allowed. Symptoms disappeared at 13 and 8 days, and a follow-up treadmill test showed normal PR interval and no heart block. No recurrence of heart block has been seen in any of these three patients. CONCLUSION: Late unexpected heart block after RFCA of AV nodal reentry and posteroseptal AP is rare, often resolves uneventfully in 1 to 2 weeks, and no specific electrophysiologic findings predicted its occurrence. Prolonged clinical observation is preferable to immediate pacemaker implantation in such patients.

Effect of myocardial hypertrophy on systolic and diastolic function in children: insights from the force-frequency and relaxation-frequency relationships.

OBJECTIVE: The objective of this study was to evaluate the effect of myocardial hypertrophy on systolic and diastolic properties of the left ventricle in children. BACKGROUND: In children with myocardial hypertrophy, ejection phase indices are invariably increased. However, indices of force-generation, e.g., end-systolic elastance and invasive indices of diastolic properties, have been studied infrequently in children with myocardial hypertrophy. METHODS: We studied 10 children with congenital aortic stenosis or coarctation of aorta and nine control patients. Systolic properties were assessed from shortening fraction, end-systolic fiber elastance (Ef(es)) measured at resting heart rates, and force-frequency relationship measured at heart rates increasing from 110 to 160 beats per minute. Diastolic properties were assessed from time constant of relaxation (tau) at matched heart rates, chamber stiffness constant, myocardial stiffness constant, and relaxation-frequency relationship measured at gradually increasing heart rates. RESULTS: Ef(es) remained unchanged by myocardial hypertrophy, however, tau was prolonged (tauL: 27.3+/-2.3 vs. 21.8+/-2.2 ms, p < 0.001; and tauD: 43.2+/-3.1 vs. 34.3+/-3.3 ms, p < 0.001). Both chamber and myocardial stiffness constants remained unchanged. Incremental increases in heart rate produced incremental improvement in both contraction and relaxation. Slopes of force-frequency and relaxation-frequency relationships remained unchanged in the experimental group. However, the relaxation-frequency relationship manifested a parallel shift upward. CONCLUSIONS: In conscious, sedated children with myocardial hypertrophy, systolic function assessed by an index of force generation remains unchanged. However, relaxation is prolonged but passive diastolic properties remain unaffected. The combined effect of hypertrophy and heart rate does not alter the force-frequency and relaxation-frequency relationships.

Electrical restitution in diseased human ventricular myocardium.

Action potential configuration and electrical restitution were studied in diseased human ventricular muscle by comparing the characteristics of hypertrophic (HYP) and dilated (DIL) human ventricular preparations. Conventional microelectrode techniques were used to evaluate action potentials evoked at increasingly longer diastolic intervals. The steady-state action potential duration (APD90) was significantly longer in DIL than in HYP preparations (393 +/- 5 ms, n = 4 and 296 +/- 11 ms, n = 4, respectively; P < 0.001, mean +/- SEM). In the dilated preparations studied at long diastolic intervals, the initial period of rapid repolarization (phase 1) was absent, and the rate of final repolarization (phase 3) was reduced. Electrical restitution relations in these preparations were fitted as the sum of two exponentials. The time constant of the fast component was significantly longer in DIL than in HYP preparations (242 +/- 9 ms and 121 +/- 4 ms, respectively; P < 0.001). No difference was observed in the time constants for the slow component of restitution in the two groups. Electrical restitution was also studied in single human ventricular myocytes by using patch clamp techniques. The initial 600 ms period of restitution was fitted in these cells to a monoexponential function. The time constant for this period of the restitution relation was significantly longer, while the estimated amplitude of this early rising phase was significantly lower in human cells obtained from DIL hearts than the respective parameters obtained in the healthy canine and guinea pig cells also examined. The observed changes in the restitution kinetics of the dilated human heart are, likely, the consequence of alterations in the ionic currents that underlie the cardiac action potential.

Cardiac abnormalities associated with hydrops fetalis.

Cardiovascular abnormalities are associated with hydrops fetalis in 26% of cases reported in the modern era. These include not only structural abnormalities, but also cardiac arrhythmias, failure, tumors, myopathy, infection, inflammation, infarction, and arterial calcification. Cardiac structural abnormalities may be causative or seen only in association with hydrops fetalis. Structural lesions that result in right atrial pressure or volume overload seem to be most commonly associated with hydrops fetalis. Fetal cardiac tumors, cardiomyopathy, myocarditis, myocardial infarction, and arterial calcification probably result in hydrops fetalis by a similar mechanism. Fetal tachyarrhythmia has been shown to result in elevation of atrial pressure and atrial natriuretic peptide. Fetal tachyarrhythmias are the most treatable of cardiac causes of hydrops fetalis. Fetal bradyarrhythmias are less easily treatable and less certainly a causative mechanism of hydrops fetalis.

Use of adenosine for diagnosis and treatment of tachyarrhythmias in pediatric patients.

This report reviews our experience with the use of adenosine for diagnosis and treatment of narrow QRS complex tachyarrhythmias in children. All electrocardiograms obtained since the introduction of adenosine for clinical use at one pediatric tertiary care institution during an 18-month period were reviewed, and those patients receiving adenosine were included for study. Of the 24 patients who received adenosine, the median age was 4 years; four neonates were included. Adenosine produced atrioventricular block in 21 (88%) of 24 patients. It terminated the tachyarrhythmia in 11 patients and produced atrioventricular block but did not terminate the tachyarrhythmia in 10 patients. The mechanism of the arrhythmia was known in three patients before adenosine administration. Adenosine was useful in establishing the mechanism of the tachyarrhythmia in 17 of the remaining 18 patients but was not useful in one patient, in whom the arrhythmia was successfully terminated because a good-quality electrocardiogram was not obtained during adenosine administration. Therefore the mechanism of the supraventricular tachycardia was ultimately determined for all patients in whom adenosine successfully produced atrioventricular block and had acceptable electrocardiographic tracings. Side effects were limited and transient. We conclude that adenosine was a safe and effective agent for the pharmacologic treatment of narrow QRS complex tachyarrhythmias in our patients, including those less than 1 year of age. If proper electrocardiographic recordings are performed during adenosine administration, it is also helpful in establishing the cause of the tachyarrhythmia.

Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of intravenous amiodarone in young patients. BACKGROUND: Oral amiodarone therapy has proved useful for problematic arrhythmias in children, but its pharmacokinetics with the oral route preclude its use in several acute settings. METHODS: Intravenous amiodarone was administered in 1-mg/kg body weight aliquots followed by continuous infusion to patients with potentially life-threatening tachyarrhythmias that had not been abolished by standard therapies. RESULTS: Ten patients (mean age 6.8 years) received intravenous amiodarone: for ventricular tachycardia in seven patients and for atrial tachycardia, junctional tachycardia and multiple arrhythmias in one patient each. Surgery for congenital heart defects had been performed previously in six patients. Two patients had a hamartoma causing ventricular tachycardia. Six of 10 patients had complete resolution of arrhythmia with intravenous amiodarone: 4 of 7 with ventricular tachycardia, 1 of 1 with atrial tachycardia and 1 of 1 with postoperative junctional ectopic tachycardia. Intravenous amiodarone was not successful in the two patients with a hamartoma but slowed ventricular tachycardia in one, allowing successful surgical cure. Average drug load at the time of effect was 4.8 mg/kg body weight. Four patients had transient hypotension during loading, corrected with volume or low dose calcium. Intravenous infusion of amiodarone, 10 mg/kg per day, continued an average of 3 days. Four of 10 patients died, all of nonarrhythmic causes not attributable to intravenous amiodarone. CONCLUSIONS: Intravenous amiodarone was well tolerated in this small series of patients. Postoperative ventricular tachycardia was responsive to intravenous amiodarone in 80% (8 of 10) of the patients (95% confidence interval 40% to 99%). Use of this drug in acute, postoperative tachyarrhythmias may be lifesaving in some patients when standard intravenous therapies fail.

Active and passive electrical properties of isolated canine cardiac Purkinje fibers under conditions simulating ischaemia: effect of diltiazem.

The effect of a calcium channel blocker diltiazem on the electrical properties of canine Purkinje fibers superfused in a milieu similar to that occurring in acute myocardial ischaemia was studied. Action potential parameters, passive electrical properties, and conduction velocity were measured using conventional microelectrode techniques. Superfusion with glucose-free Tyrode's solution containing 9 mM K+, gassed with 100% N2 at pH = 6.5 ('ischemic solution') significantly reduced the maximal diastolic potential, action potential duration, maximal upstroke velocity, conduction velocity and length constant, while input resistance and longitudinal resistance were elevated and membrane resistance remained unchanged. Diltiazem (1 microM) alone reduced only the action potential duration, while all other parameters were unaffected. Pretreatment with diltiazem did not fully prevent the effects of ischemic superfusion; however, the ischaemia-induced decrease in length constant was not significant in the presence of diltiazem. In addition, the increase in longitudinal resistance during ischaemia was significantly reduced following diltiazem pretreatment. This decrease in longitudinal resistance may contribute to the improvement of ischaemia-induced conduction delay observed in intact animals and may be related to a reduction of ischaemia-induced increase in intracellular free Ca2+.

Biphasic effect of tetraethylammonium on canine purkinje fibre action potential configuration.

1. Using conventional microelectrode techniques a biphasic effect of tetraethylammonium (5 mmol/l) on the configuration of action potentials recorded from isolated canine Purkinje fibres: action potentials were first shortened (early effect) and then lengthened (late effect) by tetraethylammonium. 2. The early effect of tetraethylammonium also included lengthening of phase 1 duration and elevation of the plateau amplitude. These early effects reached steady-state within the first 3 min of superfusion and were readily reversed within 3 min of initiating washout of the drug. 3. The late effect (gradual lengthening of repolarisation during phase 3) failed to reach steady-state within the initial 60 min of superfusion and was not reversible. 4. The early effects of tetraethylammonium were more marked at slow driving rates and were not affected by blockade of alpha- and beta-adrenoceptors using 1 mumol/l phentolamine and 1 mumol/l propranolol. 5. The early effects of tetraethylammonium were mimicked by 4-aminopyridine (0.5 mmol/l), and in the presence of 4-aminopyridine tetraethylammonium failed to induce further changes in action potential morphology. 6. The early effects of tetraethylammonium may be due to inhibition of the transient outward current. 7. The rapid onset and reversibility of these early effects suggest that tetraethylammonium may act from outside the cell membrane.

Bedside termination of sustained ventricular tachycardia by transesophageal atrial pacing.

Transesophageal atrial pacing was used to terminate hemodynamically stable sustained monomorphic ventricular tachycardia in two patients. The procedure was performed at the bedside, no anesthesia was required, there were no complications, and one of the patients went home after the procedure was performed. This method should be considered prior to using direct current cardioversion in patients with hemodynamically stable sustained monomorphic ventricular tachycardia.

Antiarrhythmic drug therapy in the management of cardiac arrest survivors.

Antiarrhythmic drugs may be used as primary therapy to prevent recurrent cardiac arrest or as adjunctive treatment in patients given an implantable cardioverter defibrillator. In the latter instance, drugs are given to suppress nonlethal arrhythmias that are capable of initiating defibrillator discharge or to slow and/or decrease the number of episodes of sustained ventricular tachyarrhythmias. When used as primary therapy, drug efficacy should be judged by nonempirical methods, preferably serial electrophysiological testing. Although no study has compared noninvasive with invasive testing to determine antiarrhythmic drug effectiveness in a substantial number of cardiac arrest survivors, several investigations have demonstrated that electrophysiological testing is useful for this purpose. One important limitation of serial electrophysiological testing is that nearly 40% of cardiac arrest survivors do not have a sustained ventricular tachyarrhythmia initiated at baseline study; nonpharmacological treatment would appear preferable in these patients. Further, since a relatively high arrhythmic recurrence rate has been noted in individuals with suppressible sustained ventricular tachycardia/fibrillation during drug therapy and a left ventricular ejection fraction less than 30%, we recommend serial electrophysiological/pharmacological testing primarily for patients with inducible sustained ventricular tachyarrhythmias with an ejection fraction greater than or equal to 30%.

Rate and concentration-dependent effects of UK-68,798, a potent new class III antiarrhythmic, on canine Purkinje fibre action potential duration and Vmax.

1. The frequency-dependent electrophysiological effects of UK-68,798 in concentrations of 1, 3, 10 and 30 nM were examined in isolated cardiac Purkinje fibres of the dog at both a number of constant rates of stimulation and following abrupt changes in pacing cycle length. 2. In all concentrations evaluated, UK-68,798 lengthened action potential duration in a concentration- and rate-dependent manner (e.g., at a cycle length = 500 ms, control APD90 = 234.0 +/- 3.3 ms, while after 10 nM UK-68,798, APD90 = 315.0 +/- 5.9 ms). 3. The duration of action potentials evoked following abrupt changes in pacing rate were also increased in a concentration-dependent manner at all diastolic intervals tested. 4. The fast and slow time constants for restitution of APD were not altered by UK-68,798. However, the amplitude terms for this relation were increased. 5. In addition, the maximum upstroke velocity (Vmax) was not significantly affected by exposure to UK-68,798 at any concentration or diastolic interval. The kinetics for recovery of Vmax were thus unaffected. 6. These findings are similar to those previously reported for recognized class III antiarrhythmic agents (e.g., bretylium, clofilium, and sotalol); however, UK-68,798 was 1,000 to 10,000 times more potent. 7. The combined potency and selectivity of this agent seem to make it an ideal tool for the investigation of cardiac potassium channels believed responsible for controlling the duration of the action potential. 8. This potent and highly selective compound may prove extremely useful in the control of cardiac arrhythmias.

Electrophysiologic effects of FPL 13210 on canine Purkinje fiber action potential duration and Vmax comparison to disopyramide.

The frequency-dependent effects of FPL 13210, a new disopyramide derivative, were examined in isolated canine cardiac Purkinje fibers paced at a frequency of 2 Hz and following abrupt changes in pacing cycle length. At 2 Hz, FPL 13210 depressed Vmax, while shortening action potential duration measured at 50% of repolarization (APD50) and not affecting duration measured at 90% of repolarization (APD90). These effects were concentration dependent over the range of 1-30 microM. The depression of Vmax produced by 5 microM FPL 13210 was not significantly different than that produced by 18 microM disopyramide while the preparations were paced constantly at 2 Hz. At these concentrations, recovery of Vmax was slowed by both FPL 13210 and disopyramide. The slow time constant estimated for this relation after exposure to FPL 13210 was approximately 6.5 times longer than that estimated following administration of disopyramide. In addition, APD90s evoked by early premature stimuli in the presence of 5 microM FPL 13210 were longer than those produced in the absence of drug when the diastolic intervals longer than 100 ms produced shorter APD90s after FPL 13210 administration. Therefore, when FPL 13210 is compared to disopyramide using concentrations selected to produce equivalent degrees of Vmax depression, FPL 13210 produced effects on APD90 that were opposite to those produced by disopyramide when the diastolic interval was longer than normal. These effects of FPL 13210 would suggest that this compound should be classified as a class Ic antiarrhythmic agent, unlike disopyramide, a class Ia antiarrhythmic agent.

Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine Purkinje fibres.

The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1-30 mumol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 mumol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 mumol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 +/- 5.2 ms (control, n = 6) to 217.1 +/- 17.8 ms (n = 6, P less than 0.05). In the presence of restacorin (10 mumol/l), a second slow component for recovery of maximal action potential upstroke rising velocity was expressed having a time constants of 8.5 +/- 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P less than 0.01) by 10 mumol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.