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Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 91 records · Page 5Linked to original sources

Short- and long-term therapy with tocainide for malignant ventricular tachyarrhythmias.

Tocainide was administered to 228 patients referred for treatment of recurrent ventricular tachyarrhythmias that were refractory to therapy with conventional antiarrhythmic drugs. After baseline studies, 1200 to 2400 mg tocainide/day was given for 4 days. Tocainide was effective in 49% of 180 patients evaluated with monitoring and exercise testing and in 35% of 48 patients undergoing electrophysiologic testing. No clinical parameter predicted the response to tocainide, although there was a correlation with the effect of lidocaine. Tocainide was selected for long-term treatment in 73 patients who were followed for an average of 26.4 months (range 1 to 92 months). The incidence of sudden death was 4.3% per year and two patients had nonfatal recurrence of arrhythmia. It is concluded that tocainide is effective and well tolerated during long-term use if therapy is evaluated carefully and is individualized.

Adolescent↗

Side effects and complications of amiodarone therapy.

To assess the incidence of adverse effects associated with long-term amiodarone therapy, we reviewed the records of 217 consecutive patients who were treated for refractory arrhythmia. After an average of 11.8 months of therapy, one or more side effects occurred in 113 patients (52%). These were considered clinically significant in 42 patients (19.3%), mandating discontinuation of amiodarone in 18 (8.3%). The untoward reactions requiring discontinuation of amiodarone included thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, and drug interactions. The mild side effects included corneal microdeposits, skin rashes, and gastrointestinal symptoms. There was a weak correlation between blood levels of amiodarone, the daily dose, and the cumulative dose (r = 0.23, p = 0.015). Drug levels were higher in symptomatic patients (p less than 0.03), although they received lower doses of amiodarone. While amiodarone is associated with frequent side effects, they are generally mild and do not necessitate drug discontinuation. Careful monitoring of therapy is essential to detect the potentially serious adverse reactions which are encountered in nearly 20% of patients.

Amiodarone↗

Aggravation of arrhythmia induced with antiarrhythmic drugs during electrophysiologic testing.

There is evidence that antiarrhythmic drugs can worsen ventricular arrhythmias in patients. In a previous study ventricular arrhythmias worsened 11% when noninvasive monitoring and exercise tests were performed to evaluate drug effect. How frequently this complication occurs when patients undergo electrophysiologic studies is not known. Electrophysiologic (EP) tests were carried out in 63 patients who had a history of malignant, sustained ventricular tachyarrhythmias. Monitoring and exercise tests showed low-frequency or nonreproducible ventricular arrhythmia. Criteria for definite drug-induced aggravation of arrhythmia included conversion of nonsustained ventricular tachycardia to a sustained ventricular arrhythmia and provocation of the end point with one extrastimulus when three were required during control. Aggravation was deemed possible when, as compared to a control group, the end point resulted with the use of one less extrastimulus and sustained tachycardia with a more rapid rate was provoked. A total of 216 single drug studies were performed (3.4/patient). In general, definite or possible aggravation occurred in 35 tests (16%). In 28 cases (12.9%) aggravation was categorized as definite, while in 7 cases (3.2%) the induced arrhythmia was deemed as possibly related to the use of the antiarrhythmic drugs. Drug tests with multiple agents caused aggravation of arrhythmia in 19 patients (30%). Therefore, exacerbation of arrhythmia by antiarrhythmic drugs also occurs during electrophysiologic study. The incidence approximates that reported when monitoring and exercise tests are used for evaluating drug efficacy.

Anti-Arrhythmia Agents↗

Propafenone: noninvasive evaluation of efficacy.

Propafenone, a new antiarrhythmic drug, was administered to 60 patients with a history of refractory ventricular tachyarrhythmias, including ventricular fibrillation in 16 and ventricular tachycardia (VT) in 44. A noninvasive protocol was followed utilizing ambulatory monitoring and exercise testing for evaluation of drug effect. The protocol involved acute drug testing with 450 mg of propafenone followed by maintenance therapy with 150 to 300 mg t.i.d. for 4 days. The protocol was completed by 57 patients; in 3 patients side effects developed that necessitated discontinuation of the drug before evaluation. When evaluated by monitoring, 34 patients (60%) responded to the drug, with total elimination of runs of VT, a greater than 90% reduction in couplets and a greater than 50% decrease in the frequency of ventricular premature beats. Based on exercise testing, 36 patients (63%) were deemed responders. When both exercise and monitoring were considered, 30 of 57 patients (53%) responded to propafenone. The acute drug test predicted the response to maintenance therapy in 84% of patients. Propafenone did not change left ventricular function in patients with normal ejection fractions (greater than 50%). However, in those with an ejection fraction less than 50%, propafenone significantly reduced this value (34% vs 29%, p less than 0.01). Side effects occurred in 20 patients (33%) and included nausea, congestive heart failure, aggravation of arrhythmia and conduction abnormalities. Eleven patients have continued on propafenone for an average of 16 months with continued efficacy and freedom from side effects.

Adolescent↗

Indications for pacing in the treatment of bradyarrhythmias. Report of an independent study group.

Indications for permanent pacing in the bradyarrhythmias are summarized. In the absence of symptoms, pacing is justified only when Mobitz type II block or complete atrioventricular (AV) block is localized in the bundle-branch system. All other abnormalities of impulse generation or conduction (incomplete AV block of any type, atrial fibrillation with slow ventricular response, or sinus node dysfunction) must be shown to be stable and intrinsic and to cause CNS symptoms or hemodynamic compromise to justify pacing. Isolated intra-Hisian abnormality without failure of AV conduction is benign. Measurement of HV interval does not contribute significant information. Correlation of carotid sinus sensitivity with carotid sinus syncope is poor (5%). Bradyarrhythmia produced by minimal effective doses of an essential drug is a rare indication for pacing and requires special documentation. Inadequate indications, sources of error, and misconceptions are discussed. Generally, it is important to exclude drug effect, transient clinical states, and correctable systemic disease as causes of the abnormality before making a conclusion about pacing.

Atrial Fibrillation↗

Effects of oral mexiletine on left and right ventricular function.

Malignant ventricular arrhythmias often occur in patients with left ventricular (LV) dysfunction. Antiarrhythmic drugs may further impair LV function in these patients. Mexiletine, a lidocaine congener, is an effective antiarrhythmic drug, but when administered orally, its effect on LV and right ventricular (RV) function is unknown. To determine the hemodynamic effects of mexiletine, LV and RV ejection fraction (EF) were measured by radionuclide ventriculography in 10 patients with LV dysfunction (LVEF less than 50%). Symptom-limited exercise tests were also performed. Patients were studied before and during therapy with oral mexiletine. There was no significant change in LVEF (28% vs 27%) or RVEF (46% vs 41%). Also, heart rate at rest, exercise duration and peak heart rate during exercise were unchanged. Thus, in patients with LV dysfunction, oral mexiletine does not significantly affect LV or RV function.

Adult↗

Management of malignant ventricular arrhythmia--experience with lorcainide.

Sudden cardiac death continues to be a major health hazard. Control of the problem requires identification of those at risk and effective therapy for prevention. Studies have shown that in patients with coronary disease or cardiomyopathy, salvos of ventricular tachycardia are an independent risk factor for sudden death. Therefore, the objective of therapy is the suppression of these forms. A large number of antiarrhythmic drugs are available, but there are no guidelines for the selection of an effective and well-tolerated agent. We have developed a systematic approach to drug selection which includes 4 phases: phase 0 is a control period to establish the prevalence and density of the arrhythmia; phase 1, acute drug testing, is designed to screen a number of drugs for effectiveness; during phase 2 the drug is administered for a brief period to evaluate efficacy and tolerance; phase 3, once the drug is determined to be well tolerated and effective, it is continued as part of a long-term program. This approach was applied in 76 patients who underwent testing with lorcainide. This drug was continued long term in 15 patients. After 23 months of follow-up, only 1 patient died suddenly. Therefore, patients with life-threatening ventricular arrhythmia can be protected from a recurrence by individualized drug therapy.

Anti-Arrhythmia Agents↗

Long-term mexiletine for ventricular arrhythmia.

Use of mexiletine was evaluated in 313 patients with ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs. Therapy with mexiletine was continued long term in 107 patients who responded to the drug and were free of side effects during a short-term evaluation in hospital. During an average follow-up of 22.8 months (0.1 to 70 months), 19 patients died (17.8%). Eleven patients had sudden death (3.6% per year), while six patients died of progressive congestive heart failure and two of noncardiac causes. Nonfatal ventricular arrhythmia recurred in 14 patients (4.9% per year). Overall, 25 patients had recurrent arrhythmia (incidence of 5.5% per year). Side effects occurred in 13 patients after an average of 5.1 months and were primarily gastrointestinal and neurologic. Sixty-one patients (57%) have continued on mexiletine therapy for an average of 32.2 months (1 to 70 months). Outcome during long-term therapy was not related to drug dose, blood level, or presenting arrhythmia. We conclude that if therapy with mexiletine is carefully evaluated and individualized, the drug is effective and well tolerated during long-term use.

Arrhythmias, Cardiac↗