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Biomedical subjects

J Morganroth

Publications and source records attributed to J Morganroth.

At least 109 records · Page 6Linked to original sources

Safety and efficacy of a twice-daily dosing regimen for moricizine (ethmozine).

Moricizine (ethmozine), a phenothiazine-related new antiarrhythmic agent previously used thrice daily, was studied to determine whether a twice daily regimen could be used with the same degree of efficacy and safety. Ten patients entered a single-blind, 35-day, placebo-controlled, outpatient longitudinal, crossover comparison using 10 to 12 mg/kg/day of moricizine. There were five 7-day phases in which the first, third, and fifth were placebo dosing and the second and fourth were randomized as to moricizine dosage regimen (every 8 hours vs every 12 hours). There were no statistically significant differences between the three placebo periods in ventricular premature complex (VPC) frequency. There was no statistically significant difference between the two dosing regimens for ventricular arrhythmia control with the first day of moricizine dosing; however, when averaging the sixth and seventh days on drug, there was a significantly greater reduction in frequency on the every 12 hour regimen compared to the every 8 hour regimen (p = 0.004). No relationship was found between the percent arrhythmia suppression and dose or plasma concentration. Six patients had transient side effects on the every 12 hour regimen vs four patients with side effects on the every 8 hour regimen. This study demonstrates that moricizine may be used every 12 hours with excellent efficacy and tolerance.

Anti-Arrhythmia Agents↗

The clinical electrophysiology of intravenous indecainide.

The electrophysiologic effects of indecainide, a new class IC antiarrhythmic agent, were assessed in 10 patients with left ventricular dysfunction and inducible sustained ventricular tachycardia. Indecainide was administered intravenously in a dose of 60 to 90 mg/kg at a rate of 12.5 to 15 micrograms/kg/min. Indecainide had no effect on sinus node function or atrial and ventricular effective refractory periods. The AH (106 +/- 13 vs 130 +/- 24 msec, p less than 0.002) and HV (57 +/- 7 vs 73 +/- 19 msec, p less than 0.001) intervals were significantly increased. The QRS duration increased (102 +/- 9 vs 120 +/- 13 msec, p less than 0.001); however, the JT duration did not change. Induction of ventricular tachycardia was prevented in 1 of 10 patients. In the remaining nine patients, the ventricular tachycardia cycle length was significantly prolonged (248 +/- 47 vs 320 +/- 71 msec, p less than 0.001). Indecainide significantly depressed intracardiac conduction at several sites.

Adult↗

A review of the uses and limitations of tocainide--a class IB antiarrhythmic agent.

In conclusion, it appears that tocainide will be an extremely important new antiarrhythmic agent in the armamentarium of the clinical cardiologist (Table V). Its similarity to lidocaine and the predictability of its efficacy in patients responsive to lidocaine is an important note. Its lack of interaction with beta blockers and digoxin is also a promising feature. While tocainide has proven to be effective in the prophylaxis and treatment of patients with both refractory and chronic ventricular arrhythmias, its efficacy is in the approximate range of other class I agents, such as quinidine, procainamide, and disopyramide. Its side effect profile appears to be similar in percentage to the adverse effects of quinidine, but often these side effects are milder, better tolerated, and respond to dosage alteration. Thus, tocainide will undoubtedly prove to be a useful new antiarrhythmic agent, particularly when compared to the currently available antiarrhythmic agents.

Animals↗

Ischemia at rest is independent of the extent of ventricular dysfunction and arrhythmias in patients with coronary artery disease.

To assess the relation between myocardial ischemia, ventricular arrhythmias (VA), and left ventricular (LV) dysfunction, we evaluated 74 patients with coronary artery disease (CAD) using radionuclide angiography (to determine the resting ejection fraction [EF]), resting thallium-201 scintigraphy (to ascertain the extent of resting ischemia), and 24-hour Holter monitoring (to assess VA). Thirty patients had resting ischemia, 26 had resting EF less than 30%, and 27 had repetitive VA. Patients with and without ischemia had similar EFs (36 +/- 14 vs 38 +/- 14, p = NS). Further, patients with and without repetitive forms of VA had a similar number of resting ischemic segments (1.1 +/- 1.7 vs 1.1 +/- 2.2, p = NS). Patients with EFs less than 30 had more VA than patients with EFs greater than or equal to 30 (Holter class 4.3 +/- 2.3 vs 3.0 +/- 1.8, p less than 0.01) but a similar extent of ischemia (1.4 +/- 2.2 vs 1.0 +/- 1.7, p = NS). Thus, while patients with lower EFs have more repetitive forms of VA, ischemia at rest is independent of VA and EF. These data suggest that prognostic stratification of patients with CAD for intervention studies should include a separate consideration of ischemia.

Arrhythmias, Cardiac↗

The value of echocardiographic regional wall motion abnormalities in detecting coronary artery disease in patients with or without a dilated left ventricle.

To evaluate the usefulness of echocardiographic regional wall motion abnormalities (RWMA) in detecting coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and a normal-sized or dilated left ventricle, 103 patients were studied by two-dimensional echocardiography (2DE) and cardiac catheterization. In 60 patients (group I) who had LV dysfunction and a dilated left ventricle by echo (patients with dilated cardiomyopathy), RWMA were detected in 44 patients and 38 (86%) of them had significant CAD, usually two- or three-vessel obstruction; of the 16 patients with dilated cardiomyopathy (DCM) and diffuse LV hypokinesis, eight (50%) had evidence of CAD. Thus the presence of RWMA by 2DE had an 83% sensitivity, a 57% specificity, and a 77% predictive accuracy in detecting CAD in patients with DCM and thus in distinguishing ischemic from idiopathic DCM. In 43 patients with LV dysfunction but normal LV size (group II), the sensitivity, specificity, and predictive accuracy of RWMA in detecting significant CAD was 95%, 100%, and 95%, respectively. We conclude that the detection of RWMA by 2DE is highly suggestive of significant CAD in patients with LV dysfunction and normal-sized or dilated left ventricle; the finding, however, of diffuse LV hypokinesis does not exclude CAD in these patients, especially when the left ventricle is dilated.

Adult↗

Acute severe mitral regurgitation. Pathophysiology, clinical recognition, and management.

Acute severe mitral regurgitation often goes unrecognized as an emergency requiring prompt, lifesaving treatment. Its causes, physical signs, natural history, echocardiographic features, and findings on chest roentgenography, electrocardiography, and nuclear scintigraphic scanning are reviewed. Acute severe mitral insufficiency can be differentiated from chronic severe mitral insufficiency by noninvasive two-dimensional echocardiography. M-mode echocardiography is a valuable tool in evaluating mitral prosthetic paravalvular regurgitation.

Acute Disease↗

Beta-Blocker Heart Attack Trial: impact of propranolol therapy on ventricular arrhythmias.

The natural history of and the effect of propranolol on ventricular arrhythmias post-myocardial infarction were analyzed using data from the Beta-Blocker Heart Attack Trial (BHAT). The Beta-Blocker Heart Attack Trial was a multicenter, randomized, double-blind, placebo-controlled trial among 3,837 patients entered from 5 to 21 days after hospitalization for acute myocardial infarction. At baseline, prior to randomization, 3,290 (85.7%) patients underwent 24-hr ambulatory ECG monitoring which was repeated in approximately 25% of a randomly selected subset of the study population at 6 weeks. Ventricular arrhythmias were divided into eight different categories which defined the prevalence of ventricular arrhythmias in terms of frequency and/or complexity. Ventricular arrhythmias at baseline were associated with age, past history of myocardial infarction, and use of diuretics and digitalis. Paired data (baseline and 6-week) were available for 428 patients on propranolol and 412 on placebo. Propranolol markedly blunted the two- to threefold increase in ventricular arrhythmias that occurred from baseline to 6 weeks in the placebo group. Propranolol decreased the proportion of patients having ventricular arrhythmias during waking hours compared with sleep. These data show that propranolol has an antiarrhythmic effect and suggest that an antiarrhythmic mechanism may in part be responsible for the observed reduction in sudden cardiac death mortality in BHAT.

Adult↗

The effect of telemetry on urban prehospital cardiac care.

A three-year, controlled trial of the use of telemetry in the prehospital care of cardiac patients was conducted in a major metropolitan area. Five of the ten paramedic squads in the city used telemetry; the other five squads did not. We studied the effect of telemetry on the following: paramedics' abilities to recognize ECGs in a written test; paramedics' abilities to identify ECG arrhythmias in the field; length of time spent by paramedics in the field; survival rates of patients with ventricular fibrillation (VF) cared for by paramedics; abilities of base station physicians to interpret telemetered ECGs; and attitudes of paramedics toward using telemetry. Telemetry was not found to affect the abilities of paramedics to read ECGs in either test or field situations. Paramedics who used telemetry spent more time in the field with their patients than did paramedics who did not use telemetry (P less than .02). We found no statistically significant effect of telemetry on survival rates of VF patients. Using matched ECGs, readings by base station physicians were found to be more accurate than were those by paramedics (P less than .01). Paramedics overwhelmingly reported that telemetry did not help them to save patients' lives, but that it did help them to treat patients with certain arrhythmias. The results suggest that telemetry may not improve either paramedics' abilities to identify arrhythmias or prehospital care for all cardiac patients. The implications for emergency services researchers are discussed.

Allied Health Personnel↗

Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy.

The efficacy of amiodarone was assessed in 38 patients with atrial fibrillation resistant to quinidine and an effort made to identify factors correlated with amiodarone response. The study group included 29 patients with and 9 without organic heart disease and either persistent (n = 11) or paroxysmal (n = 27) atrial fibrillation. All patients were treated with amiodarone and followed up in a research clinic. Efficacy was classified as excellent (no recurrent symptomatic atrial fibrillation) in 15 (55%) of 27 patients with paroxysmal and 5 (45%) of 11 patients with persistent atrial fibrillation. Efficacy was poor (no effect on atrial fibrillation) in 5 (19%) of 27 patients with paroxysmal and 6 (55%) of 11 patients with persistent atrial fibrillation. Efficacy was good (amelioration but not total suppression) in 7 (26%) of 27 patients with paroxysmal atrial fibrillation. Efficacy was related to echocardiographic left atrial dimension, left ventricular ejection fraction and, in patients with persistent atrial fibrillation, the duration of the arrhythmia. During the follow-up period of 15 months (range 1 to 36), overall efficacy (considering response and toxicity) was 67% in the 27 patients with paroxysmal and 45% in the 11 patients with persistent atrial fibrillation. It is concluded that amiodarone offers an additional therapeutic alternative in quinidine-resistant atrial fibrillation and that certain clinical factors are correlated with amiodarone response.

Adult↗

Electrophysiologic testing in patients at high risk for sudden cardiac death. I. Nonsustained ventricular tachycardia and abnormal ventricular function.

Nonsustained ventricular tachycardia, although usually asymptomatic, is associated with a high risk of sudden cardiac death in patients with depressed left ventricular function. To test the vulnerability of such patients to symptomatic and potentially life-threatening arrhythmias, complete electrophysiologic studies were performed in 58 patients with clinically documented nonsustained ventricular tachycardia (greater than or equal to three complexes but less than 15 seconds of self-terminating ventricular tachycardia by 24 hour ambulatory electrocardiographic [Holter] or telemetric monitoring) and abnormal left ventricular function (ejection fraction less than 50% by radionuclide angiography). All patients had nonsustained ventricular tachycardia in the absence of antiarrhythmic drugs, acute ischemia, long QT syndrome, recent infarction or electrolyte abnormalities. The stimulation protocol for each patient included the introduction of single, double and triple ventricular extrastimuli at three cycle lengths (sinus, 600 and 450 ms) and two right ventricular sites (apex and outflow tract). A sustained ventricular tachyarrhythmia was induced in 23 patients (40%) and a nonsustained ventricular tachycardia in 14 patients (24%). Induction of sustained tachycardia correlated with the presence of akinesia or aneurysm, or both, by radionuclide angiography, but not with ejection fraction or presence or absence of coronary artery disease. These results indicate that: 1) patients with clinical nonsustained ventricular tachycardia and chronic left ventricular dysfunction have a high incidence of inducible sustained ventricular tachycardia or ventricular fibrillation; and 2) electrophysiologic testing may allow further substratification of risk of sudden cardiac death in high risk patients with nonsustained ventricular tachycardia.

Adult↗

Comparative evaluation of antiarrhythmic agents.

The clinical drug armamentarium has been markedly expanded in recent years providing the physician with an increasing choice of antiarrhythmic agents to treat the needs of particular patients. Individually guided therapy is still the hallmark in the use of antiarrhythmic drugs, particularly with the wide variability of efficacy and toxicity and differing mechanisms of pharmacoelectrophysiological actions. The newest of the class I antiarrhythmic agents, the so-called: 'cainides' (Ic) appear to be particularly useful in testing the hypothesis that stabilisation of electrical instability may be an important goal if the high rate of sudden cardiac death is to be prevented. From the new tools available to the investigator (electrophysiological and Holter models, and many new antiarrhythmic agents), new approaches to the prevention of sudden death will emerge (Horowitz and Morganroth, 1982).

Adrenergic beta-Antagonists↗

Ambulatory Holter electrocardiography: choice of technologies and clinical uses.

Rapid growth in the use and complexity of Holter monitoring technologies has resulted in the diverse recorders and analysis devices that are compared in this review. Holter recording modes include continuous recording, which makes all electrocardiographic (ECG) data available for analysis; patient-activated recording, which is useful for capturing infrequent symptomatic arrhythmias; and event recording, which provides data on ECG events detected by the recorder, but whose reliability is limited. Various sophisticated, computer-based analysis systems exist, with varying prices and degrees of accuracy and reliability. Quantitative data are essential in the use of Holter monitoring to define the response of ventricular arrhythmias to therapeutic interventions, but the physician must be wary of quantitative data unless a quality-control program has been established and validated. Although Holter monitoring is safe, problems in recording and in differentiating artifacts from true cardiac rhythm disturbances may result in false clinical diagnoses unless these problems are recognized.

Ambulatory Care↗

Tocainide: a new oral antiarrhythmic agent.

Tocainide, a newly released class 1B antiarrhythmic agent, has membrane stabilizing and electrophysiologic characteristics similar to those of lidocaine, but it can be prescribed for oral administration. Investigational studies in both animals and humans have shown tocainide's effectiveness for the treatment of ventricular arrhythmias in chronic and acute settings. The drug has nearly 100% bioavailability after oral administration and an effective half-life of 9 to 37 hours (mean, 15 hours). Antiarrhythmic efficacy is similar to that of other class I medications currently in use. Serious side effects most frequently involve the central nervous or gastrointestinal system and occur in 10% to 20% of patients. Tocainide has minimal negative inotropic effects and a tendency to shorten effective refractory periods.

Administration, Oral↗

Efficacy and safety of intravenous tocainide compared with intravenous lidocaine for acute ventricular arrhythmias immediately after cardiac surgery.

In this double-blind parallel study, 99 patients with acute ventricular tachyarrhythmias after open-heart surgery were given either tocainide (50 patients) or lidocaine (49 patients) intravenously as 2 bolus injections 15 minutes apart, plus a fixed-rate infusion that started at the first bolus. If needed, a third bolus was administered and simultaneously the infusion rate was doubled. The boluses and initial infusion rate for tocainide treatment were, respectively, 250, 250 and 125 mg and 1.04 mg/min, and for lidocaine treatment, 100, 50 and 50 mg and 2.08 mg/min. When efficacy was defined as 80% or greater reduction in single ventricular premature complexes (VPCs) or complete abolition of ventricular couplets or ventricular tachycardia, no difference in efficacy between the 2 treatments was found by bedside electrocardiographic monitoring. By computer analysis of 24-hour taped electrocardiograms and a regression analysis of the proportion of patients responding favorably to treatment, it was estimated that an 80% or greater reduction of single VPCs occurred in 55% of patients during tocainide treatment and in 48% of patients during lidocaine treatment; abolition of couplets occurred in 74% and 68% of patients, respectively; and abolition of ventricular tachycardia in 87% and 73% of patients, respectively. These treatment-related differences were different (p less than 0.004). Adverse reactions occurred in 5 patients (10%) given tocainide (hypotension in 4; junctional rhythm in 1 patient; and nausea-vomiting in 1) and led to discontinuation of treatment in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Flecainide: its proarrhythmic effect and expected changes on the surface electrocardiogram.

The proarrhythmic potential and electrophysiologic effect of flecainide acetate, a potent class IC anti-arrhythmic agent, are considered in this report. Although the definition of a proarrhythmic effect is arbitrary, several such definitions are discussed and applied to data on flecainide. In patients with chronic ventricular arrhythmias, an increase in VPC frequency developed in 0 to 4% of patients, compared with 1 to 8% of patients who received quinidine and 2% who received encainide, another class IC agent. In patients with acute hemodynamically significant ventricular arrhythmias, the proarrhythmic effects were noted in 5 to 12%. Proarrhythmic effects appear to be more common in patients with left ventricular dysfunction and life-threatening ventricular arrhythmias. The depression of atrioventricular conduction produced by flecainide is similar to that seen with other class IC agents. Increases in PR and QRS intervals are related to dose and plasma concentration and are approximately 25% at therapeutic levels. These changes in the electrocardiographic intervals do not appear to carry important clinical implications and do not require discontinuation of flecainide. QT prolongation is absent or minimal with flecainide. Guidelines for management of patients with flecainide are suggested.

Anti-Arrhythmia Agents↗