Selection of antiarrhythmic drugs based on electrophysiologic studies.
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Amiodarone↗
Biomedical subjects
E N Prystowsky
Publications and source records attributed to E N Prystowsky.
Antiarrhythmic and electrophysiologic effects of oral propafenone.
Twenty-six patients had ventricular tachycardia initiated at control electrophysiologic study and had a repeat study during oral propafenone therapy. Ten patients had had sustained ventricular tachycardia, 6 cardiac arrest and 10 symptomatic, nonsustained ventricular tachycardia. Twenty-two patients had heart disease, 18 of whom had coronary artery disease. During propafenone therapy, ventricular tachycardia could not be initiated during programmed ventricular stimulation in 5 patients, and in 21 patients the cycle length of induced ventricular tachycardia increased from 246 +/- 42 ms at control to 355 +/- 96 ms (p less than 0.001). Seventeen patients were discharged with propafenone therapy and have been followed for a mean of 11 months. No symptomatic ventricular tachycardia recurred in the 5 patients without inducible ventricular tachycardia during drug treatment. Six of 12 patients with inducible ventricular tachycardia during the drug study have remained asymptomatic. In conclusion, propafenone substantially prolongs the cycle length of ventricular tachycardia, and initiation of ventricular tachycardia by programmed ventricular stimulation at drug study does not preclude a favorable clinical outcome.
Adult↗
Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy.
Propafenone was administered to 29 patients who had multiple episodes of recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) despite previous antiarrhythmic therapy. All patients had 24-hour continuous electrocardiographic recording and electrophysiologic study in a drug-free control state and while receiving maximum doses of propafenone. During propafenone treatment, the mean frequency of ventricular premature complexes (VPCs) decreased 74% (p less than 0.05). There was more than an 83% decrease in VPC frequency in 17 of 29 patients, and 11 patients had 99 to 100% decreases. Propafenone prevented VT induction at electrophysiologic study in 6 patients, whereas another 12 patients were judged to have satisfactory electrophysiologic responses on the basis of slower VT rates and absence of hemodynamic compromise during VT. After long-term treatment from 2 to 26 months, 9 patients continued propafenone without evidence of recurrent arrhythmia. Six of these 9 patients had not VT induction at electrophysiologic study while receiving propafenone. The decrease in VPC frequency produced by propafenone was a poor predictor of a successful electrophysiologic study and of long-term therapy. In conclusion, propafenone has potential as an effective antiarrhythmic agent, but better methods to stratify risk for recurrence of VT and VF are needed.
Adult↗
Development of the implantable transvenous cardioverter.
The development of the transvenous cardioverter, from the initial animal studies, to the clinical studies using temporary leads, to the initial permanent implants is described. Shocks less than or equal to 2.0 joules synchronized to the QRS complex and delivered through a specially designed catheter electrode placed in the apex of the right ventricle successfully terminate most episodes of ventricular tachycardia in patients. The implanted unit which also serves as a demand ventricular pacemaker, can be used to perform programmed electrophysiologic studies. Future devices must be capable of defibrillation and more accurate arrhythmia detection.
Aged↗
Early experience with an implantable cardioverter.
We tested the efficacy and safety of a fully programmable cardioverter weighing 95 g, in terminating sustained ventricular tachycardia. The device was implanted tranvenously under local anesthesia in seven patients. On command from a programmer or automatically, the cardioverter delivered shocks through a lead inserted to the apex of the right ventricle. It also served as a demand ventricular pacemaker and could perform programmed ventricular stimulation or overdrive pacing. Cardioversion of ventricular tachycardia required less than 0.5 J (mean) and was well tolerated by the patients, who were awake and not sedated. In one patient, a shock terminated ventricular tachycardia with the device in the automatic mode but produced atrial fibrillation with a rapid ventricular response that was intermittently recognized as ventricular tachycardia, triggering additional shocks. One such shock in the ST segment produced ventricular fibrillation that was terminated transthoracically in the emergency room, without residual impairment. We conclude from these preliminary observations that cardioversion of sustained ventricular tachycardia by means of an implantable catheter device is feasible, but for the present its use in the automatic mode must be cautious and selective. The unit's small size, ease of implantation, usefulness for noninvasive electrophysiologic studies, programmability, and bradycardia pacing functions are advantages. The next-generation device must be able to defibrillate and provide better differentiation of arrhythmias.
Adult↗
Functional bundle branch block: discordant response of right and left bundle branches to changes in heart rate.
Faster heart rates shorten refractoriness more in some tissues than in others. This study investigates whether faster heart rates shorten relative refractoriness more in the right than left bundle branch in humans. Premature atrial stimulation at 2 or more basic cycle lengths was performed in 314 patients with no evidence of atrioventricular conduction system disease. In 10 patients, both functional right and left bundle branch block (BBB) developed with premature atrial stimulation. Functional right BBB occurred at the longer basic cycle length, and functional left BBB at the shorter cycle length in 8 patients. In 2 patients functional right and functional left BBB were present at the same cycle length, but functional left BBB occurred at a shorter premature atrial coupling interval. For all patients, the mean functional right bundle branch relative refractoriness was 438 ms at a basic cycle length of 847 ms, and functional left bundle branch relative refractoriness was 357 ms at a cycle length of 622 ms (p less than 0.01). The HV interval was 45 +/- 15 ms at control and increased with functional left BBB to 77 +/- 19 ms (p less than 0.01), but not with functional right BBB. Thus, relative refractoriness of the right and left bundle branches are rate-dependent and discordant. At longer cycle lengths, relative refractoriness of the right bundle branch is greater than that of the left bundle branch, and at shorter cycle lengths relative refractoriness of the left bundle branch is greater than that of the right bundle branch. The relative refractory period curves "cross over" and can explain the presence of both functional right and left BBB in the same patient.
Adolescent↗
Plasma and red blood cell concentrations of amiodarone during chronic therapy.
Amiodarone and a metabolite, desethylamiodarone, were measured in plasma of 55 patients and in both plasma and red blood cell (RBC) in 28 patients who received chronic amiodarone treatment. The assay for amiodarone and desethylamiodarone was performed by high-pressure liquid chromatography. During chronic treatment, median plasma concentration of amiodarone was 2.80 micrograms/ml and desethylamiodarone was 2.20 micrograms/ml. In matched samples, plasma amiodarone concentration exceeded RBC amiodarone concentration (p less than 0.001) and the RBC-to-plasma concentration ratio averaged 0.31. The plasma desethylamiodarone concentration was not significantly different from its RBC concentration, and the RBC-to-plasma concentration ratio averaged 1.29. There was a linear correlation between plasma concentrations of amiodarone and desethylamiodarone (r = 0.82) and between RBC concentrations of drug and metabolite (r = 0.71). Drug or metabolite concentrations in plasma and RBCs correlated directly with daily dosage of amiodarone. Adverse side effects during chronic amiodarone therapy were related most strongly to RBC drug and metabolite concentrations. The group with adverse side effects had a significantly higher RBC concentration of amiodarone, 150 vs 0.75 micrograms/ml (p less than 0.001), than did patients free of adverse effects. After dosage reduction, side effects abated and plasma and RBC concentrations of drug and metabolite decreased. These data indicate that there is an expected range of amiodarone and desethylamiodarone concentrations during chronic treatment and that adverse side effects correlate best with RBC concentrations of drug and metabolite. Red cell concentrations may reflect the amount of unbound, free amiodarone and desethylamiodarone in plasma.
Amiodarone↗
Concealed conduction preventing anterograde preexcitation in Wolff-Parkinson-White syndrome.
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Atrioventricular Node↗
Prolongation of the QT interval induced by probucol: demonstration of a method for determining QT interval change induced by a drug.
Sudden death has occurred in monkeys fed large doses of probucol, a cholesterol-lowering drug, given in combination with an atherogenic diet. These monkeys develop prolonged QT intervals and high serum levels of probucol. We investigated the effect of probucol on QT interval and the incidence of ventricular ectopy during a double-blind placebo-controlled study in 16 patients with less than 600 premature ventricular complexes (PVCs) per day and a corrected QT interval of less than 0.44 second. Seven patients received probucol and nine patients received placebo. Three 24-hour continuous ECG recordings were obtained prior to entry into the study and three additional recordings were obtained after 6 months of drug or placebo therapy. A 15-second ECG tracing was sampled from the continuous ECG recording every 30 minutes and, for the group, 15,000 QT intervals were measured permitting construction of QT versus R-R regression lines for each patient before and during therapy. Comparison of the regression lines revealed that the measured QT interval prolonged 20 +/- 18 msec during the awake state and 24 +/- 20 msec during sleep (mean + standard deviation) at matched heart rates in the seven patients receiving probucol (p less than 0.01). Using Bazett's formula to correct for rate, corrected QT interval prolonged 22 +/- 23 msec in the awake state and 20 +/- 18 msec in the asleep state (p less than 0.01). In probucol treated patients QT interval prolongation was directly related to increasing probucol plasma levels (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evaluation of the patient with wide QRS tachycardia.
Acute and long-term therapy as well as prognosis in patients with wide QRS tachycardia differ depending on the mechanism of the arrhythmia. Twelve-lead electrocardiography and prolonged electrocardiographic monitoring are often diagnostic. However, additional techniques such as esophageal and right atrial electrocardiography, or His bundle electrocardiography with detailed electrophysiologic studies, are sometimes necessary to delineate the mechanism of the arrhythmia.
Adult↗
Clinical use and pharmacology of amiodarone.
Amiodarone, an investigational drug in the United States, has had considerable use in this country and worldwide in the treatment of cardiac arrhythmias. This article reviews the clinical pharmacology of this potentially useful antiarrhythmic agent.
Amiodarone↗
Preexcitation syndromes. Mechanisms and management.
Ventricular preexcitation occurs when, in relation to atrial events, some or all of the ventricular muscle is activated earlier by the atrial impulse than would be expected if conduction of the impulse activated the ventricles by way of the normal atrioventricular conduction system. The purpose of this article is to review the pathophysiology of the variants of preexcitation and to discuss the therapeutic approach to patients who have tachyarrhythmias.
Anti-Arrhythmia Agents↗
Clinical efficacy and electrophysiologic effects of cibenzoline therapy in patients with ventricular arrhythmias.
Cibenzoline, a new antiarrhythmic agent, was tested in 26 patients who had symptomatic ventricular tachycardia (24 patients) or premature ventricular complexes (2 patients) unresponsive to conventional drugs. Cibenzoline was given orally every 8 hours to maximal doses of 65 mg in 2 patients, 81.25 mg in 22 patients and 97.5 mg in 2 patients. Cibenzoline abolished spontaneous episodes of ventricular tachycardia in 8 of 16 patients with ventricular tachycardia during a 72 hour control electrocardiographic recording, and 7 of 22 patients had greater than 83% decrease in premature ventricular complexes compared with control. The PR interval increased 14% (p less than 0.001), QRS duration increased 17% (p less than 0.001), QT interval did not change and mean ejection fraction in 10 patients did not change. Electrophysiologic studies were performed on 10 patients in the control period and during maximal cibenzoline dosage. Cibenzoline did not affect electrophysiologic properties of the atrium or atrioventricular (AV) node. It prolonged the ventricular effective (223 +/- 16 to 241 +/- 22 ms, p less than 0.02) and functional (247 +/- 18 to 264 +/- 25 ms, p less than 0.02) refractory periods. At control electrophysiologic studies, ventricular tachycardia was induced in 9 of 10 patients (mean cycle length 210 +/- 31 ms). Cibenzoline therapy prevented ventricular tachycardia induction in two patients, and in the other seven patients the mean ventricular tachycardia cycle length increased from 210 to 260 ms. The one patient with no ventricular arrhythmia induced during the control study still had no arrhythmia induced while receiving cibenzoline.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects.
Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.
Administration, Oral↗
Synchronous intracardiac cardioversion.
The concept of synchronous transvenous cardioversion of sustained ventricular tachycardia is discussed. This article reviews the animal experience, initial and collective studies in patients, and results of permanent implantation in two patients.
Aged↗
Future directions: electrical therapy for cardiac tachyarrhythmias.
Directions and research opportunities in basic animal and clinical investigations and in industry that relate to the application and development of electrical devices which control tachyarrhythmias are presented. In basic research, a better understanding of mechanisms responsible for tachyarrhythmias , their onset and methods of termination, would provide increased rationale for selecting a particular therapeutic approach. Knowing the distribution in the heart of applied electrical current when delivered by different types of electrodes placed at different myocardial sites would be helpful. Clinically, we must develop appropriate algorithms to accurately differentiate sinus tachycardia, the various forms of supraventricular tachycardias and ventricular tachycardia. These must be incorporated into future cardioverters and defibrillators . In industry, new sensors, electrodes, expanded telemetry capabilities and implanted microprocessors will aid in creation of a universally applicable generic form of electrical therapy that can be programmed to treat any form of tachycardia.
Animals↗
Initial experience with Symbios Model 7008 pacemaker.
The Symbios 7008 pacemaker is capable of treating both bradycardias and tachycardias. In this report, we summarize operation of the pacemaker and the initial experience in 21 patients who have received implants. All patients have supraventricular tachyarrhythmias that have been terminated successfully with automatic atrial burst pacing (19 patients) or AV sequential pacing. More than half of the patients also have bradyarrhythmias requiring pacing and thus benefit from both functions of the device. Experience to date has been favorable.
Adult↗
Preliminary experience with the implantable transvenous cardioverter.
A synchronized shock of less than or equal to 2.0 joules delivered over a specially designed catheter electrode passed to the apex of the right ventricle effectively terminates sustained ventricular tachycardia in dogs and in patients. The capability has been engineered into a 95 gram device implanted using lidocaine anesthesia, which is also capable of VVI pacing and of performing programmed electrophysiologic studies. Seven patients have received the implant and the initial experience is described.
Aged↗