Response to programmed ventricular stimulation: sensitivity, specificity and relation to heart disease.

This prospective study of 100 patients evaluated the sensitivity and specificity of the repetitive ventricular response and ventricular tachycardia induced by programmed electrical stimulation for identifying patients with spontaneous ventricular tachyarrhythmias. The influence of underlying heart disease on such sensitivity and specificity was also evaluated. The repetitive ventricular response was sensitive (92 percent) for detecting patients with prior spontaneous ventricular tachyarrhythmias, but lacked specificity (57 percent); the rate of false positive responses was 43 percent.

Quinidine and digoxin. An important interaction.

An increase in serum digoxin concentration occurs in 90% of patients given quinidine. On average, the serum digoxin doubles during treatment with therapeutic doses of quinidine. Almost every patient treated with quinidine will have a decrease in the renal clearance of digoxin and many will have a decrease in the volume of distribution of digoxin.

Antiarrhythmic effect of imipramine hydrochloride in patients with ventricular premature complexes without psychological depression.

A study was performed in cardiac patients without psychological depression to determine (1) the antiarrhythmic efficacy of imipramine, (2) its half-life of elimination and duration of action, and (3) the frequency of adverse effects. Twenty-two patients with 30 or more ventricular premature complexes/hour entered the protocol. A drug-free and a placebo day were followed by dosing with imipramine, 1 mg/kg per day, given in two divided doses.

Factors related to orthostatic hypotension associated with tricyclic antidepressants.

A group of 45 depressed patients treated with imipramine hydrochloride were examined in an attempt to identify factors that might influence the risk of developing orthostatic hypotension. Although the literature suggests that age and/or heart disease influences the occurrence of orthostatic hypotension, these conclusions are controversial. To pursue this issue, a sample of older depressed patients, many with severe cardiovascular disease, was chosen.

Four-contact glove probe method for rapid recording of cardiac electrograms during surgery.

A technique is presented for recording four simultaneous electrograms from the heart during operation for cardiac arrhythmias. this technique permits intraoperative maps of cardiac electrical activity to be constructed more rapidly than is possible with single-point mapping, thereby decreasing the risks to the patient and yielding more information about cardiac events.

Which postinfarction ventricular arrhythmias should be treated?

There is still no consensus on which arrhythmias should be treated in the 6- to 12-month high-risk period after acute myocardial infarction. To examine this question, we analyzed 24-hour ECG recordings in 430 patients who survived for at least 2 weeks after myocardial infarction and studied these patients for at least 1 year. During the year after infarction, 63 cardiac deaths occurred.

Mechanisms of quinidine-induced depression of maximum upstroke velocity in ovine cardiac Purkinje fibers.

A major advance in understanding how quinidine depresses maximum upstroke velocity (Vmax) is the Hondeghem-Katzung mathematical model which incorporates voltage-independent rate constants for binding to and unbinding from resting, open, and inactive Na channels, and a voltage shift of -40 mV for the Hodgkin-Huxley h-kinetics of quinidine-associated Na channels. Using a double microelectrode voltage clamp technique to control transmembrane voltage and apply conditioning pulses, we found that quinidine blockade increased as transmembrane voltage became more positive in the range -60 to +40 mV, and that the rate of quinidine dissociation increased as transmembrane voltage became more negative in the range -60 to -140 mV. The relationship of Vmax to transmembrane voltage obtained at drive cycles from 500 msec to 20 seconds conformed to the model modified to include voltage-dependent rate constants without the postulated -40-mV shift for quinidine-associated channels.

Electrophysiologic effects of procainamide on sinus function in patients with and without sinus node disease.

To compare the effects of procainamide on sinus node (SN) function in the presence (seven patients) and absence (nine patients) of SN dysfunction, sinus cycle length (SCL), maximal corrected sinus recovery time (maximal CRST), paced cycle length yielding peak SN suppression (PCLp), and indirect sinoatrial conduction time (SACT) were determined before and after intravenous administration of 10 to 15 mg/kg procainamide in each patient. Plasma procainamide concentration was in the therapeutic range in all patients. The mean SCL did not change significantly in either group (-24 +/- 58 and -73 +/- 171 msec for patients with normal and abnormal SN function, respectively).

Clinical and electrophysiologic characteristics of sinoatrial entrance block evaluated by direct sinus node electrography: prevalence, relation to antegrade sinoatrial conduction time, and relevance to sinus node disease.

When AV conduction is normal, the absence of VA conduction is not abnormal. Analogous information about retrograde sinoatrial conduction is not available. Although the premature atrial stimulas (PAS) technique can demonstrate the presence of sinoatrial entrance block (SAEB), both its prevalence and its relationship to antegrade SA conduction are unknown.

Quinidine-digoxin interaction: time course and pharmacokinetics.

The time course of the rise in serum digoxin concentration was followed in 18 patients treated with digoxin as quinidine treatment was started with a loading dose. The mean serum digoxin levels rose significantly during the first 24 hours after administration of quinidine was begun, and reached a new steady state concentration after about 48 hours. Digoxin kinetics were studied in two groups of normal volunteers: Group 1 (n = 7) received a small dose of quinidine, 800 mg/day, and group II (n = 8) received 1,600 mg/day.

Prevalence, characteristics and significance of ventricular tachycardia (three or more complexes) detected with ambulatory electrocardiographic recording in the late hospital phase of acute myocardial infarction.

A 24 hour electrocardiographic recording was performed before hospital discharge in 430 patients who survived the cardiac care unit phase of acute myocardial infarction. Fifty patients (11.6 percent) had ventricular tachycardia, that is, three or more consecutive ventricular complexes.

Risk stratification with low-level exercise testing 2 weeks after acute myocardial infarction.

We enrolled 250 patients with acute myocardial infarction after they had been discharged from the cardiac intensive care unit. Among 236 patients who performed a low-level exercise test just before hospital discharge, 52 (22%) had exercise-induced ST depression of at least 0.1 mV in ECG lead V5, 102 (43%) had ventricular arrhythmias, and 121 (51%) had an exercise capacity of shorter than 6 minutes.

Cardiovascular effects of therapeutic doses of tricyclic antidepressants. A review.

Overdose of tricyclic antidepressants (TCAs) leave no doubt that TCA drugs at high concentrations have serious cardiac effects. It has been assumed that, to a lesser extent, these effects would occur at usual therapeutic concentration. Recent prospective, plasma-level-controlled studies have improved our understanding of these drugs and proved these assumptions to be inaccurate.

Analysis of prognostic significance of ventricular arrhythmias after myocardial infarction. Shortcomings of Lown grading system.

The Lown grading system for ventricular arrhythmias has been used in observational and experimental studies of ischaemic heart disease. This grading system uses three levels of ventricular premature depolarisation frequency and four complex features to assign patients to one of seven grades. We tested several of the major assumptions of the Lown grading system in a group of 400 patients who had recently experienced acute myocardial infarction.

Sinus node dysfunction caused by methyldopa and digoxin.

Symptomatic sinus bradycardia developed in two patients while they were taking methyldopa and digoxin. In one patient, bradycardia did not occur with either digoxin or methyldopa alone. The other patient, who had never taken methyldopa alone, did not demonstrate bradycardia with digoxin alone.

The effects of thioridazine on electrical and ischemic ventricular fibrillation in the dog heart in situ.

Lethal ventricular arrhythmias have occurred in patients taking thioridazine. Therefore, we studied two canine models to determine if thioridazine alters vulnerability to ventricular fibrillation. In 30 chloralose-anesthetized dogs, the repetitive response threshold was used to assess vulnerability during right ventricular stimulation with transvenous catheter electrodes.

Shortcomings of the Lown grading system for observational or experimental studies in ischemic heart disease.

The Lown grading system uses three levels of frequency and four complex features to grade ventricular arrhythmias. The seven Lown grades are mutually exclusive (a patient can be in only one grade) and hierarchical (higher grades indicate increased likelihood of death). We evaluated the ability of the Lown arrhythmia grading system to predict death in 400 patients who were convalescing from acute myocardial infarction.

The human sinus node electrogram: a transvenous catheter technique and a comparison of directly measured and indirectly estimated sinoatrial conduction time in adults.

To improve methods for evaluating human sinus node function (SNF), we developed a transvenous electrode catheter technique for direct recording of sinus node electrograms in adults. Sinus node electrograms (SNE) characterized by low-frequency, anatomically localized pre-P-wave potentials were obtained in 19 of 23 patients. The SNE configuration was similar to that previously found for endocardial SNE recordings in in vitro atrial preparations, in open-chest dogs and during human open heart surgery.

Efficacy, plasma concentrations and adverse effects of a new sustained release procainamide preparation.

To assess the efficacy, plasma drug concentrations and adverse effects of a new sustained release preparation of procainamide, 33 patients with heart disease were studied in an acute dose-ranging protocol and a chronic treatment protocol. Patients initially received a daily dose of 3 g of sustained release procainamide; this dose was increased by 1.5 g daily until ventricular premature depolarizations were suppressed by 75 percent or more, adverse drug effects occurred or a total daily dose of 7.