Biomedical subjects

H J Duff

Publications and source records attributed to H J Duff.

At least 109 records · Page 6Linked to original sources

PubMed1987

A randomized clinical trial of the noninvasive and invasive approaches to drug therapy of ventricular tachycardia.

There is controversy over whether therapy to prevent ventricular tachyarrhythmias should be selected noninvasively (by trying drugs and monitoring the patient electrocardiographically) or invasively (by selecting a drug that prevents induction of the arrhythmia by programmed stimulation). We randomly assigned 57 patients with symptomatic and demonstrable ventricular tachyarrhythmias to therapy selected either noninvasively or invasively. The tachyarrhythmias involved were sustained ventricular tachycardia (35 patients), nonsustained ventricular tachycardia with hypotension (15 patients), and ventricular fibrillation (7 patients). The noninvasive approach sought reduction of ventricular premature beats by more than 80 percent and of couplets by more than 90 percent, with elimination of three or more successive ventricular beats on ambulatory monitoring and exercise testing. The invasive approach sought to prevent the induction of five or more repetitive beats by programmed stimulation. The noninvasive approach required fewer drug trials (3.2 +/- 1.8 [mean +/- SD] vs. 5.5 +/- 2.8, P less than 0.001) and fewer hospital days (20 +/- 15 vs. 33 +/- 24, P = 0.01) and identified a therapy predicted to be effective for more patients than did the invasive approach (29 of 29 vs. 15 of 28, P less than 0.001). When a predicted effective therapy was not found, amiodarone was prescribed despite persisting inducibility of ventricular tachycardia. Patients randomly assigned to the noninvasive approach had more symptomatic recurrences of tachyarrhythmia than those treated by the invasive approach (two-year actuarial probabilities of 0.50 +/- 0.10 vs. 0.20 +/- 0.08, P = 0.02). Similar differences were observed when amiodarone recipients were excluded. There were only three deaths from recurrent ventricular tachyarrhythmias--two in the group whose treatment was selected noninvasively and one in the group whose treatment was selected invasively (not significant). We conclude that therapy selected by the invasive approach prevents recurrences of ventricular tachyarrhythmias better than that selected by the noninvasive approach.

Anti-Arrhythmia Agents↗

PubMed1987

Procainamide, disopyramide and quinidine: discordant antiarrhythmic effects during crossover comparison in patients with inducible ventricular tachycardia.

A crossover comparison of intravenous procainamide, disopyramide and quinidine was made in 32 patients. All three drugs had dosage-related effects on electrocardiographic intervals, refractory periods and cycle length of ventricular tachycardia. Significant linear relations between serum drug levels and changes in refractory periods and ventricular tachycardia cycle length were also observed. Ventricular tachycardia was no longer inducible on at least one drug in 11 patients but concordance of this effect on both of the others was 36% and on either of the others it was 45%. Ventricular tachycardia remained inducible on at least one drug in 28 patients and concordance of this effect on both of the others was 75% and on either of the others was 79%. Continued inducibility on quinidine, the drug producing the greatest electrophysiologic effects, was the best individual predictor of continued inducibility on the others. Subdivision of continued inducibility into easier to induce, inducibility unchanged, or harder to induce dramatically decreased concordance of this effect. Thus the antiarrhythmic effects of these drugs are discordant in individual patients despite electrophysiologic similarities. Nevertheless, continued inducibility after high dosages of any one of these drugs is clinically useful for screening for continued inducibility on the others and this is dose-related rather than drug specific.

Adult↗

PubMed1987

Mexiletine-quinidine combination: electrophysiologic correlates of a favorable antiarrhythmic interaction in humans.

Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone. The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles. Ventricular tachycardia could no longer be induced in 7 (35%) of the 20 patients studied with combination therapy. This was a significantly higher proportion of patients than that of the groups responding to either monotherapy (quinidine, 10%; mexiletine, 5%). Ventricular effective and functional refractory periods were measured when applying single (S2), double (S3) and triple (S4) extrastimuli. Quinidine monotherapy increased functional and effective refractory periods of both single and multiple extrastimuli. However, when comparing measurements made during mexiletine treatment with those at baseline, mexiletine monotherapy increased only the refractory periods of S4. The effective refractory period of S4 during mexiletine monotherapy (200 +/- 20 ms) was significantly longer than at baseline (160 +/- 21 ms). Similarly, when comparing measurements made during combination therapy with those during quinidine monotherapy, combination therapy significantly increased the refractory periods only of multiple extrastimuli. The effective refractory period of S4 during combination therapy (253 +/- 26 ms) was significantly longer than that of quinidine monotherapy (223 +/- 27 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Electropharmacology of sotalol in patients with Wolff-Parkinson-White syndrome.

The beta-adrenoceptor-blocking and class III effects of sotalol were assessed in 11 patients with inducible orthodromic reciprocating tachycardia. Serum sotalol concentration, maximum exercise heart rate, and electrophysiologic study data were obtained at control, at the beta-adrenoceptor-blocking dosage (407 +/- 149 mg/day, 1.4 +/- 0.5 micrograms/ml), and at the maximum well-tolerated dosage (924 +/- 337 mg/day, 3.2 +/- 1.3 micrograms/ml). Class III effects (increases in anterograde and retrograde accessory connection effective refractory periods, ventricular effective refractory period, and the QT interval during fixed-rate atrial pacing) were evident at the beta-adrenoceptor-blocking dosage of sotalol and became more marked at the maximum well-tolerated dosage. For example, the mean anterograde accessory connection effective refractory period was significantly increased over control (272 +/- 41 msec) by the beta-adrenoceptor blocker (324 +/- 52 msec) and was further significantly increased by the maximum well-tolerated dose (364 +/- 37 msec). Similarly, the minimum preexcited RR interval during atrial fibrillation was increased in all patients at each dosage tested. Antiarrhythmic efficacy, defined by the absence of inducible, sustained, orthodromic reciprocating tachycardia and a minimum preexcited RR interval during atrial fibrillation of 300 msec or greater, was achieved in four patients at the beta-adrenoceptor-blocking dosage and in another four patients at the maximum well-tolerated dosage. These eight patients received long-term sotalol therapy and none has had recurrent, sustained reciprocating tachycardia during 15 +/- 12 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

A receptor for type I antiarrhythmic drugs associated with rat cardiac sodium channels.

We assessed the effects of type I antiarrhythmic drugs on the binding of ligands to receptors on voltage-sensitive sodium channels of rat cardiac myocytes. The radioligand was [3H]batrachotoxinin A 20 alpha-benzoate ([3H]BTXB), a toxin that binds to the sodium channel. The 8 drugs tested inhibited [3H]BTXB binding in a dose-dependent fashion with IC50 values from 1.34 microM for O-demethylencainide to 811 microM for procainamide. A log-log plot of IC50 versus mean therapeutic serum concentration yielded a regression line with slope of 1.17 and r of 0.95. Scatchard analysis of [3H]BTXB binding showed that lidocaine reduced the maximal binding without altering the KD for [3H]BTXB binding, indicating allosteric inhibition. The inhibition by lidocaine of [3H]BTXB binding was reversible within 30 minutes when the samples were diluted from 390 to 39 microM lidocaine. In other studies, the stereoisomers of tocainide were shown to have a threefold to fourfold difference in IC50 for inhibition of [3H]BTXB binding. The binding of antiarrhythmic drugs to this site is saturable, reversible, and stereospecific and occurs at pharmacologically relevant concentrations with similar rank order of potency in vivo and in vitro. This suggests that binding at this site relates to pharmacologic activity.

Animals↗

PubMed1987

Evaluation of a therapeutic drug monitoring program for theophylline in a teaching hospital.

Studies concerning the value of therapeutic drug monitoring programs for theophylline have yielded contradictory findings. This study employed a prospective, single-blind, randomized, crossover design to evaluate the effect of a therapeutic drug monitoring program for theophylline. There were 410 serum theophylline assays performed in 169 patients. The average number of assays drawn incorrectly and the average number of assays used inappropriately were significantly reduced (from 1.87 to 1.32 and from 2.07 to 1.45, respectively) with therapeutic drug monitoring. When the program was withdrawn, no statistically significant change resulted, and when the program was reinstituted, there was improvement in audit criteria performance but the change was not statistically significant. Although the savings from the program would equal the cost in the first year, cost savings would be anticipated in the future.

Biological Assay↗

PubMed1987

Impact of a therapeutic drug monitoring program for digoxin.

Although numerous utilization reviews of serum digoxin assays have demonstrated the positive impact of therapeutic drug monitoring, to our knowledge, the question of whether the withdrawal of such a program would reverse the effect has not been addressed. The current study employed a prospective, randomized, crossover design to evaluate this question and document the cost savings. There were 196 serum digoxin assays performed in the 207 patients. It was found that a continuous therapeutic drug-monitoring program was warranted since, after its withdrawal, there was a deterioration in audit criteria performance. Reimplementation of the therapeutic drug-monitoring program resulted in a significant decrease in the average number of assays requested per patient (from 1.41 to 0.73) and an improvement in audit criteria performance.

Canada↗

PubMed1986

Usefulness of noninvasive studies for diagnosis of right ventricular dysplasia.

The value and limitations of echocardiography and cardiac scintigraphy in the diagnosis of right ventricular (RV) dysplasia were assessed. Criteria that defined RV dysfunction were developed first using data from 40 normal subjects. The sensitivity and specificity of these criteria to detect RV dysplasia were then determined in 44 patients suspected of having RV dysplasia. In these patients the presence (14 patients) or absence (30 patients) of RV dysplasia had been established using cardiac catheterization data, which included contrast RV cineangiograms. Mean RV end-diastolic and end-systolic diameters, and RV/left ventricular (LV) ratios of end-diastolic and end-systolic diameters and end-diastolic and end-systolic volumes were greater in patients with RV dysplasia (p less than 0.001). Using cardiac scintigraphy, all patients with RV dysplasia were identified by an RV/LV end-systolic volume greater than 1.8; exercise RV ejection fraction less than 50%; or exercise RV wall motion score more than 1. Using echocardiography, RV contraction abnormalities were seen in 80% of patients with RV dysplasia. The specificities, even in this selected population, were less than 100%. Thus, normal echocardiographic and scintigraphic results can be used instead of RV contrast cineangiography to exclude the diagnosis of RV dysplasia.

Adult↗

PubMed1986

Concentration-dependent pharmacologic properties of sotalol.

Sotalol is a nonselective beta-receptor antagonist that prolongs action potential duration and refractoriness in vitro at higher concentrations than those associated with heart rate slowing. To determine if this additional action can be expressed in humans, 17 patients with chronic stable ventricular premature complexes were studied. Each patient was hospitalized and arrhythmia frequency was quantified during a 48-hour drug-free baseline and during every third day of therapy with increasing incremental sotalol dosages. The dosages were 160, 320, 640 and 960 mg/day, administered in 1 or 2 doses. An index of action potential duration, the rate-corrected QT (QTc), was measured using serial 12-lead electrocardiograms on the third day of each dosage at presumed steady state and the degree of beta-receptor blockade was assessed by the reduction of the maximal exercise-induced heart rate. Of the 17 patients, 11 had an antiarrhythmic response (70 to 100% reduction in VPCs), at a wide range of plasma concentrations (340 to 3,440 ng/ml). The responders to sotalol included 8 patients in whom therapy with conventional beta-receptor antagonists had failed. In the group as a whole, the concentration associated with significant QTc prolongation (2,550 ng/ml) was greater than that associated with 50% reduction of the maximal slowing in heart rate (804 ng/ml). Sotalol was generally well tolerated, but in 1 nonresponder torsades de pointes developed 3 hours after the first 640-mg dose at a plasma sotalol concentration well within the concentration range measured in other patients. Sotalol's repolarization-prolonging actions are seen at higher concentrations than those associated with heart rate slowing and may contribute to its clinical effects.

Arrhythmias, Cardiac↗

PubMed1986

Programmed electrical stimulation studies for ventricular tachycardia induction in humans. I. The role of ventricular functional refractoriness in tachycardia induction.

Closely coupled extrastimuli are frequently necessary to induce ventricular tachycardia at electrophysiologic study. Although induction usually requires propagated extrastimuli, systematic evaluations of minimal coupling intervals have focused on nonpropagated measures (effective refractory periods) rather than on propagated measures (functional refractory periods). The effects of procedural factors on ventricular functional refractory periods were examined in 10 patients. Like the effective refractory period, the functional refractory period shortens with rapid pacing cycle lengths (281 +/- 12 ms at a cycle length of 600 ms; 260 +/- 15 ms at a cycle length of 400 ms) and with multiple extrastimuli (279 +/- 16 ms with one extrastimulus; 214 +/- 16 ms with two extrastimuli). The effects of multiple extrastimuli exceed those of shortening pacing cycle length. Unlike the effective refractory period, the functional refractory period is affected by recording site (increasing as the distance from the pacing site increases) but is not affected by increasing the stimulus intensity above twice diastolic threshold (282 +/- 14 ms at 2 times threshold; 282 +/- 13 ms at 16 times threshold) or by increasing the pulse width above 2 ms (282 +/- 13 ms at a pulse width of 2 ms; 282 +/- 14 ms at a pulse width of 5 ms). The effect of varying stimulus intensity on ventricular tachycardia induction was examined in a second group of 11 patients with documented, spontaneous ventricular tachycardia. No change in ventricular tachycardia inducibility accompanied changes in stimulus intensity from 2 to 10 times threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Programmed electrical stimulation studies for ventricular tachycardia induction in humans. II. Comparison of indwelling electrode catheter and daily catheter replacement.

Suppression of the ability to induce ventricular tachycardia by programmed electrical stimulation during serial drug testing has been used as a therapeutic end point to identify long-term prophylactic antiarrhythmic therapy. However, ventricular tachycardia induction, particularly with an indwelling electrode catheter, has not been systematically assessed over the time period required for serial drug testing. In this study, the results of programmed electrical stimulation were evaluated daily during serial drug-free conditions before testing various antiarrhythmic drugs. Twenty-four patients were randomly allocated to be studied with the electrode catheter left in place or replaced daily. All patients had inducible sustained ventricular tachycardia during the first study. Loss of the ability to induce ventricular tachycardia occurred in 8 of 13 patients whose catheter was left in place whereas this did not occur in patients whose catheter was replaced daily (p less than 0.01). In addition, use of an in situ catheter was accompanied by significant (p less than 0.05) changes in other electrophysiologic measurements, including number of extrastimuli required to induce ventricular tachycardia and length of ventricular functional and effective refractory periods. The serial changes seen with indwelling catheters in the drug-free state may mimic effective antiarrhythmic drug action.

Adult↗

PubMed1986

Antiarrhythmic efficacy of propranolol: comparison of low and high serum concentrations.

Propranolol has been effective in suppressing ventricular arrhythmias in up to 70% of patients in some series; however, a wide range of concentrations was required to produce this degree of efficacy. In one series, 40% of responders required high serum concentrations (greater than 500 ng/ml) in excess of those required for physiologic beta-receptor blockade (25 to 150 ng/ml). To assess the relative contribution of high concentration electrophysiologic effects to antiarrhythmic efficacy the results of programmed electrical stimulation were compared at high and low (beta-blocking) concentrations in 28 patients with inducible sustained ventricular tachycardia. Propranolol was given as a series of loading and maintenance infusions producing first a mean concentration of 130 +/- 72 ng/ml (beta-blocking) and then a mean concentration of 743 +/- 523 ng/ml (high). Beta-blockade was assessed by the percent reduction in exercise-induced tachycardia. Near maximal beta-blockade was achieved by a concentration of 150 ng/ml. At a low concentration, 6 of 28 patients had a response to propranolol (complete in 5 and partial in 1). At a high concentration, one additional patient had a complete response while three had a partial antiarrhythmic response. At high concentrations of propranolol there was a significant shortening of the QTc interval relative to that seen during the low dose infusion. No other significant electrophysiologic changes occurred at high versus low concentration. In summary, an antiarrhythmic response to propranolol occurs most frequently at a beta-blocking concentration. High concentration electrophysiologic effects occur and these appear to contribute to antiarrhythmic efficacy in some patients.

Adult↗

PubMed1986

Binding of [3H]batrachotoxinin A benzoate to specific sites on rat cardiac sodium channels.

Radiolabeled neurotoxins have been used to study the structure and function of sodium channels. We studied the binding of [3H] batrachotoxinin A 20 alpha-benzoate [( 3H]BTX-B) to specific sites on sodium channels on rat cardiac myocytes. Calcium-tolerant myocytes were prepared by collagenase dispersion of adult rat hearts and were 75-83% viable. As with the nerve channel, specific binding of [3H]BTX-B to its receptor site was seen only in the presence of sea anemone toxin (ATX). The affinity of ATX for its binding sites may be estimated from its concentration-dependent stimulatory effect on [3H]BTX-B binding. These results suggest that, in the presence of 5.4 mM KCl, the myocytes have two affinities for ATX with estimated dissociation constants of 0.52 microM and 12.9 microM. Depolarization of the myocytes with either 65 mM KCl or 0.1 mM BaCl2 results in the loss of the 0.52 microM component, suggesting that it is voltage sensitive. The 0.52 microM and 12.9 microM components have maximal binding capacities corresponding to 4 and 11 sites/micron 2 of myocyte surface area, respectively. Scatchard analysis of [3H]BTX-B binding in the presence of ATX demonstrates a single class of sites with a KD of 25-35 nM. These results demonstrate that [3H]BTX-B can be used as a radioligand probe of the adult rat sodium channel and will facilitate a biochemical approach to the study of the interaction between antiarrhythmic drugs and the sodium channel.

Animals↗

PubMed1985

Spectrum of antiarrhythmic response to encainide.

Encainide is effective in suppressing non-life-threatening ventricular arrhythmias; however, inconsistent results have been noted in patients with more serious ventricular arrhythmias. Thirty-seven patients with drug-resistant ventricular arrhythmias were studied. Patients in group I (n = 11) has sustained ventricular tachycardia and those in group II (n = 26) had nonsustained ventricular arrhythmias. In group I, 8 patients had remote myocardial infarction, congestive heart failure and sustained ventricular tachycardia requiring repeated cardioversion (group Ia). None of these patients responded to encainide treatment, but 6 did have an antiarrhythmic response (complete in 3 and only partial in 3) to other investigational antiarrhythmic agents. Three patients in group I, all without ischemic heart disease (group Ib), had an excellent antiarrhythmic response to encainide, as did 21 of 26 patients in group II. In 4 of 5 patients in group II who did not respond, the dosage was limited due to the development of sinus pauses, atrioventricular block or bundle branch block, and in 3 of these 4 patients preexisting conduction disease was evident (PR longer than 0.2 second or QRS longer than 0.12 second). Diplopia occurred while taking the maximal oral dosage in the fifth patient. At 21.5 months of follow-up, 14 of the original 24 patients who responded to encainide continue to receive it; 3 have died (all due to natural progression of left ventricular dysfunction) and encainide was discontinued in 7: in 2 because of syncope, in 2 because of new-onset atrial fibrillation, in 1 patient because of exercise-induced polymorphic ventricular tachycardia, in 1 because of diplopia and in 1 because of skin exanthem.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗

PubMed1985

Bretylium: relations between plasma concentrations and pharmacologic actions in high-frequency ventricular arrhythmias.

Although it is widely assumed that the early arrhythmogenic and pressor responses to bretylium are caused by catecholamine release from the adrenergic neuron, this assumption has not been systematically studied in humans. Pharmacologic responses to a placebo infusion and 3 separate bretylium infusions (2.5, 5.0, 10 mg/kg over 60 minutes) were assessed in 6 patients with recurrent, nonsustained ventricular tachycardia. Plasma bretylium concentration, blood pressure (BP), plasma norepinephrine (NE) concentration, arrhythmia frequency and adrenergic neuronal blockade (assessed by the presence or absence of reflex venoconstriction) were measured. Adrenergic blockade was seen with every bretylium infusion and at a time when relatively small amounts of bretylium had been administered (range 160 to 750 mg, median 252). Temporal relations (p less than 0.03) were noted among the time of onset of adrenergic neuronal blockade, onset of the pressor response, increase in NE plasma concentration and increase in ventricular arrhythmia frequency. BP responses during the infusions were linearly related to change in plasma NE at the time of development of adrenergic neuronal blockade. Bretylium plasma concentrations higher than 3 micrograms/ml were frequently associated with a short-lived pressor response. There was a significant relation (p less than 0.06) between the increase in plasma NE during the infusion and an increase in ventricular arrhythmia frequency. Reduction in arrhythmia frequency was seen in only 1 patient, beginning 6 hours after the development of adrenergic neuronal blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Intravenous quinidine: relations among concentration, tachyarrhythmia suppression and electrophysiologic actions with inducible sustained ventricular tachycardia.

A computer simulation was used to devise quinidine sulfate infusions to produce pseudo-steady-state concentrations in the low (8 microM/liter) and high (14 microM/liter) therapeutic ranges, avoiding high peak concentrations. Using this infusion, efficacy and electrophysiologic actions of quinidine sulfate were assessed in 21 patients with sustained inducible ventricular tachycardia (VT) when concentrations were 12.6 +/- 11 microM/liter (mean +/- standard deviation) and 18 +/- 9 microM/liter. Although mean concentrations approximated target levels, there was substantial individual variation. A reciprocal linear relation (r = 0.8, p less than 0.01) was noted between resultant serum concentrations and drug-free ejection fraction (EF). Transient hypotension occurred early in 3 patients, 2 of whom had a normal left ventricular (LV) EF. No hemodynamic compromise was seen in patients with LVEFs of less than 30%. Induced VT was suppressed in 5 patients at low concentrations and in an additional 4 at high concentrations (total 9 of 21, 42%). Concentration-dependent changes in the ventricular effective refractory period of the beat induced by S3 paralleled antiarrhythmic efficacy. Independent of response or lack of response to intravenous quinidine, 17 patients received gradually increasing oral quinidine dosages adjusted to reproduce plasma levels that had been effective during intravenous administration, or to maximal well-tolerated dosage (if side effects occurred). VT was still inducible during oral treatment in 4 of 5 patients in whom VT had been suppressed during the intravenous infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1984

Differential effects of O-demethyl encainide on induced and spontaneous arrhythmias in the conscious dog.

Encainide is highly effective in suppressing most nonsustained ventricular arrhythmias, but there is evidence that the drug is less effective and may worsen some arrhythmias, particularly in patients with sustained ventricular tachycardia. In most patients it is likely that the major antiarrhythmic effects of encainide are mediated through a potent metabolite, O-demethyl encainide. The effects of infusions of saline solution or O-demethyl encainide on spontaneous ventricular ectopic activity and ventricular fibrillation (VF) threshold were compared in 25 dogs with a mottled myocardial infarct produced by transient coronary occlusion. Plasma levels of the metabolite above 100 ng/ml suppressed (greater than 92%) the spontaneous ventricular ectopic activity that occurred 48 hours after MI, whereas saline solution had no effect. In 15 dogs treated with O-demethyl encainide, the VF threshold decreased an average of 23%, from a baseline level of 23 +/- 8 mA to 18 +/- 9 mA (p less than 0.05). There was a concentration-dependent fall in VF threshold with plasma concentrations of O-demethyl encainide above 150 ng/ml. In 2 dogs with very high plasma concentrations of the metabolite (greater than 1,000 ng/ml), VF was induced by right ventricular pacing alone (S1S1 300 ms). No change in VF threshold was observed in the 8 dogs treated with saline solution, and in each of these dogs VF could be terminated by the countershock protocol. However, in 7 of the 17 dogs treated with O-demethyl encainide, VF could not be terminated by the countershock protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗

PubMed1984

Flecainide dose-response relations in stable ventricular arrhythmias.

Flecainide acetate was evaluated in a placebo-controlled, dose-ranging study performed in patients with stable, high-frequency ventricular arrhythmias. Three centers studied 35 patients in a 3-stage protocol. After a placebo baseline, increasing oral dosages from 100 to 300 mg twice daily were evaluated. Placebo was then reinstituted and after arrhythmia had recurred, the patients were discharged on the effective dosage to return to the clinic for evaluation 7 and 14 days later. Thirty of 35 patients had more than 80% suppression (mean 96%) of ventricular premature complexes (VPCs) and more than 95% reduction in complex VPCs. Arrhythmia suppression was seen at dosages of 100 to 200 mg twice daily in 73% of the patients. Twenty-three percent of patients required 500 to 600 mg/day. Mild side effects were seen in 46% of patients. These resolved or became tolerable at lower dosages in most patients. Effective therapy continued for 2 years in 24 of 29 patients, without any evidence of chronic toxicity. Pharmacokinetic studies indicate that many patients require 5 to 7 days of constant dosing before reaching steady state. Flecainide acetate is an effective antiarrhythmic with a narrow range of effective dosages.

Adult↗