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Biomedical subjects

E L Pritchett

Publications and source records attributed to E L Pritchett.

At least 19 recordsLinked to original sources
PubMed1992

Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.

Atrial Fibrillation↗
PubMed1992

Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Administration, Oral↗
PubMed1992

Treatment of paroxysmal supraventricular tachycardia with oral diltiazem.

Symptomatic paroxysmal supraventricular tachycardia is a troubling arrhythmia for many patients. To test the efficacy of oral diltiazem to reduce symptomatic recurrences of paroxysmal supraventricular tachycardia, we enrolled 17 patients in a double-blind, placebo-controlled crossover study. Sixteen of 17 patients completed a dose-ranging phase and were entered into the randomized phase. Although the time to first recurrence of tachycardia was slightly longer when patients took diltiazem, the difference was not significant (p = 0.15). The hazard ratio of the time to first recurrence on placebo compared with oral diltiazem was 2.7 (95% confidence interval, 0.8 to 9.1). Of the patients who had a recurrence of tachycardia in both treatment periods, the median reduction in heart rate in patients receiving diltiazem was 20 beats/min. (p less than 0.01; 95% confidence interval, 6 to 42).

Administration, Oral↗
PubMed1991

Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias.

In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias.

Adult↗
PubMed1991

Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy.

OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias.

Adult↗
PubMed1991

Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group.

The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2).

Adult↗
PubMed1991

Regular ventricular rhythms in patients with symptomatic paroxysmal atrial fibrillation.

Paroxysmal atrial fibrillation is a grossly irregular tachycardia. Forty-nine patients with paroxysmal atrial fibrillation who were taking a variety of antiarrhythmic medications including the class IC agents propafenone and flecainide were followed up for a median of 371 days with use of transtelephonic electrocardiogram (ECG) monitoring to document symptomatic rhythms. Eighteen patients had 96 episodes of regular tachycardia; the cumulative incidence rate was 25% at 6 months, 33% at 1 year and 41% at 18 months. Eighty of the 96 episodes occurred with a heart rate less than or equal to 180 beats/min and could have been explained by atrial flutter with 2:1 block. However, nine patients had a total of 16 episodes with a rate greater than 180 beats/min that were probably not due to atrial flutter with block; the cumulative incidence rate of these fast regular tachycardias was 14% at 6 months, 17% at 1 year and 25% at 18 months. QRS duration during the first episode of regular tachycardia was significantly longer in patients taking a class IC drug (median 105 vs 90 ms, p less than 0.001 Wilcoxon rank sum test). In contrast to drug therapy with amiodarone or the combination of digoxin and verapamil, the QRS duration of regular tachycardias during class IC therapy was directly related to the tachycardia heart rate (Spearman's rank, p less than 0.01). All episodes of fast, regular tachycardias with a QRS duration greater than 120 ms occurred in patients taking a class IC drug. Clinicians treating patients with paroxysmal atrial fibrillation should expect a substantial incidence of regular tachycardia in addition to atrial fibrillation.

Adult↗
PubMed1991

Flecainide acetate prevents recurrence of symptomatic paroxysmal supraventricular tachycardia. The Flecainide Supraventricular Tachycardia Study Group.

Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope.

The Holter monitor, the most frequently used diagnostic test in patients with syncope, is nondiagnostic in over 90% of cases. This study sought to determine the impact of a new noninvasive device, the cardiac loop electrocardiographic (ECG) recorder, after Holter monitoring in 57 patients with unexplained syncope. All patients underwent a standardized evaluation protocol and were the monitor for up to 1 month. In 14 patients, loop recording definitively determined whether an arrhythmia was the cause of symptoms (diagnostic yield 25%; 95% confidence intervals 14 to 38%). Diagnoses included unsuspected ventricular tachycardia (1 patient), high grade atrioventricular block (2 patients), supraventricular tachycardia (1 patient), asystole or junctional bradycardia from neurally mediated syncope (3 patients) and normal cardiac rhythms (the remaining 7 patients). Follow-up of all patients diagnosed as having nonarrhythmic syncope by loop recording showed that none of these patients died suddenly. Cardiac loop ECG recording is an important new diagnostic test in patients with syncope unexplained by Holter monitoring.

Arrhythmias, Cardiac↗
PubMed1990

Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry.

The occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia (PSVT) has been well documented when PSVT is secondary to atrioventricular reentry, but not when PSVT is secondary to atrioventricular nodal reentry (AVNRT). Seventeen patients with AVNRT were followed using transtelephonic electrocardiogram monitoring to document symptomatic tachycardias. The median length of telephone monitor surveillance was 357 days. Fifteen of 17 patients transmitted electrocardiograms that showed PSVT. Three of 17 patients (18%) transmitted electrocardiograms that showed atrial fibrillation. A transition from PSVT into atrial fibrillation was not recorded, but all three did have PSVT recorded on other days of follow-up. We report the occurrence of atrial fibrillation in patients with AVNRT and that its incidence is higher than expected for the general population.

Atrial Fibrillation↗
PubMed1989

Random and nonrandom behavior of symptomatic paroxysmal atrial fibrillation.

Little is known about the behavior of symptomatic paroxysmal atrial fibrillation (AF). The nature of the process formed by the successive occurrences of this arrhythmia was studied in 8 patients with a history of symptomatic paroxysmal AF. Trans-telephonic monitoring of the electrocardiogram was used to document the cardiac rhythm during symptoms. Patients were followed while successive attacks of paroxysmal AF were documented. A minimum of 12 and a maximum of 26 consecutive episodes of symptomatic paroxysmal AF were recorded from the 8 patients during 66 to 332 days. Methods developed in industrial reliability theory were used to show that, for the overall group of 8 patients, the interevent times between successive occurrences of symptomatic AF were not independent. However, for a subgroup including 6 of the patients, the interevent times were independent and governed by an exponential probability distribution. Differences in observed behavior of symptomatic AF may relate to differences in underlying mechanism within patients.

Adult↗
PubMed1989

Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

Atrial Fibrillation↗
PubMed1988

Clinical behavior of paroxysmal atrial tachycardia.

Paroxysmal atrial tachycardia is a familiar arrhythmia that has been studied extensively for the past decade using intracardiac recording and programmed electrical stimulation. These studies have thoroughly documented the mechanisms of this arrhythmia and its associated atrioventricular conduction abnormalities, but little is known about the spontaneous clinical behavior of this arrhythmia. A group of 34 patients with paroxysmal atrial tachycardia were studied using telephone transmission of the electrocardiogram to document recurrent tachycardia. When antiarrhythmic therapy was withdrawn, median time to the first recurrence of tachycardia was 19 days, mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats/min, and the median duration of an attack was 20 minutes. In a group of patients who were followed while many consecutive attacks were documented, the time intervals between attacks were found to be uncorrelated and to fit an exponential probability distribution (i.e., the occurrence of paroxysmal atrial tachycardia behaved like a Poisson process). Paroxysmal atrial tachycardia does not occur in a chaotic and unpredictable fashion; it is an event that occurs according to common probability models.

Electrocardiography↗