Search

To assess the peripheral vascular effects of estrogen in women without coronary disease, normal postmenopausal women (mean age 56 +/- 8 years) participated in a randomized, crossover trial using treadmill exercise echocardiography, and received oral conjugated estrogen, 0.625 mg/day or underwent a drug-free period. There was no significant effect on heart rate, blood pressure, double product, left ventricular end-systolic and end-diastolic diameters, or electrocardiographic measures after estrogen. In contrast to the profound effects reported in patients with cardiac disease, oral estrogen in normal women does not bestow significant benefit on treadmill exercise echocardiographic variables at rest or during modest levels of exercise.

Atrial fibrillation is the most common sustained arrhythmia reported in the United States; an estimated 1-2 million Americans have chronic nonvalvular atrial fibrillation. This disorder is associated with a substantial risk of stroke. Several recent studies provide evidence that anticoagulation therapy is indicated for stroke prevention in patients with nonvalvular atrial fibrillation after recovery from a minor stroke. Clinical and echocardiographic criteria help to identify those patients who are at especially high risk for thromboembolic stroke and are candidates for carefully controlled anticoagulation. In an effort to reduce the possibility of thromboembolic events following either chemical or electrical cardioversion, the American College of Chest Physicians has recently prepared guidelines for the use of anticoagulation in the conversion of atrial fibrillation. The efficacy of antiarrhythmic drug therapy for cardioversion is often difficult to assess. Furthermore, it is associated with major risks, including heart failure and exacerbation of arrhythmia, and minor risks, including systemic intolerance. A new National Institutes of Health trial, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), will clarify the true risks and benefits of antiarrhythmic therapy for conversion of atrial fibrillation to sinus rhythm. Patients who cannot tolerate drug therapy may benefit from interruption of conduction in the bundle of His, followed by implantation of a permanent pacemaker, the use of radiofrequency energy ablation, or the implantation of an atrial defibrillator. Some patients may benefit from surgical procedures, such as left atrial isolation, the corridor operation, and the maze operation.

Indecainide, a new type Ic antiarrhythmic agent, and quinidine sulfate were compared in a randomized double-blind parallel study. Cardiac patients with greater than or equal to 30 ventricular premature complexes per hour hour received indecainide, 50 mg, or quinidine, 200 mg every 6 hours, and the doses were increased until more than 80% suppression was noted, adverse effects occurred or a maximal dose of 100 mg of indecainide or 400 mg of quinidine given every 6 hours. Efficacy was achieved in 8 of 10 taking indecainide (p less than 0.05) and 7 of 9 taking quinidine (p less than 0.05). At least 90% of episodes of ventricular tachycardia were suppressed in 4 of 7 patients taking indecainide and 1 of 4 taking quinidine. No adverse effects were observed in the 7 patients who responded to indecainide and the 4 who responded quinidine, resulting in short-term efficacy without adverse effects in 7 patients (70%) taking indecainide and 4 (44%) taking quinidine. The effective or maximal mean daily indecainide and quinidine doses were 190 +/- 32 mg and 1,022 +/- 291 mg, respectively; mean trough indecainide and quinidine concentrations were 617 +/- 247 ng/ml and 3.3 +/- 1.4 micrograms/ml, respectively. Indecainide prolonged mean PR and QRS intervals (p less than 0.05), but not QT and QTc intervals. Quinidine did not change PR or QRS intervals but prolonged QTc interval (p less than 0.05). During dosing, 1 patient discontinued indecainide treatment because of nausea; 3 discontinued quinidine because of gastrointestinal complaints.(ABSTRACT TRUNCATED AT 250 WORDS)

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 7.5 g of sustained-release procainamide was reached. Twenty-five patients (76 percent) had at least a 75 percent reduction (range 75 to 100percent [mean +/- standard deviation 91 +/- 8.2]) in ventricular permature depolarization frequency at a dosage of 4.8 +/- 1.46 g/day (range 3.0 to 7.5). Despite the 8 hour dosing interval, the variation between maximal and minimal plasma procainamide and N-acetylprocainamide concentrations under steady state conditions was very small. Mean maximal procainamide and N-acetylprocainamide plasma concentrations were 10.4 +/- 6.02 and 12.0 +/- 7.40 micrograms/ml, respectively. The respective mean minimal concentrations were 6.8 +/- 4.50 and 8.7 +/- 5.99 micrograms/ml. In nine patients (27 percent) treatment with sustained release procainamide resulted in conversion of the antinuclear antibody test from negative to positive. Adverse drug effects occurred in 17 (52 percent) of the subjects. In general, adverse effects were minor and abated within 24 hours after administration of the drug was stopped. One patient had the procainamide-induced systemic lupus erythematosus-like syndrome.

A case of symptomatic sick sinus syndrome is presented with confirmation of sinus nodal dysfunction established by functional testing. The validity of such provocative testing and the criteria for abnormality are discussed. A newly recognized, seemingly "paradoxical" and potentially detrimental effect of atropine noted in this patient is examined. Despite an increase in sinus rate and an improvement in sinoatrial conduction time after administration of atropine, a markedly prolonged sinus recovery time after rapid atrial pacing occurred, and atrial quiescence for more than 10 seconds was seen. Possible electrophysiologic mechanisms for this phenomenon, such as decreased atriosinus entrance block, concealed sinoatrial reentry or enhanced intranodal depolarization, are discussed and potential clinic correlates are made.

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. The dose was increased by 1 mg/kg per day every other day until ventricular premature complexes were suppressed by at least 80 percent, adverse drug effects were encountered or a total daily dose of 5 mg/kg per day was given. Each day a 24 hour continuous electrocardiogram was recorded to determine the frequency of ventricular premature complexes and heart rate. During the acute dose-ranging period, 18 patients (82 percent) had an antiarrhythmic effect from imipramine. Two patients received 5 mg/kg per day without any decrease in the frequency of ventricular premature complexes. The half-life of elimination of imipramine (parent compound) was 8.8 +/- 3.72 hours but its duration of action was much longer. Four patients (18 percent) had treatment discontinued because of troublesome adverse effects during a follow-up period of 19 +/- 8.8 months. It is concluded that imipramine is a potent antiarrhythmic drug with a long duration of action and relatively few major adverse effects.

The acute phase reactant, alpha-1-acid glycoprotein, binds to a number of basic antiarrhythmic drugs, including lidocaine, quinidine, propranolol, imipramine and disopyramide. Binding to alpha-1-acid glycoprotein accounts for a decrease in free drug fraction and may alter the expected concentration: response relation of drugs particularly when there are unpredictably large or rapid changes in alpha-1-acid glycoprotein. To determine the time course and magnitude of alpha-1-acid glycoprotein for 1 month after acute myocardial infarction (AMI), blood samples were collected from 27 patients, 14 with AMI and 13 with a chest pain syndrome but no AMI. Patients with AMI had a significant increase in alpha-1-acid glycoprotein after 72 hours (mean 153 +/- 35 mg/dl) (p less than 0.05), and the maximum was observed on day 7 (mean 165 +/- 53 mg/dl) (p less than 0.05), returning to baseline by 28 days. There was no significant change in alpha-1-acid glycoprotein in patients with chest pain but no AMI. Regression analysis showed a significant relation between creatine kinase (p less than 0.005) and lactic dehydrogenase (p less than 0.001) vs alpha-1-acid glycoprotein indicating alpha-1-acid glycoprotein concentration is high in patients with large AMI. Changes in binding resulting from alpha-1-acid glycoprotein during AMI could account for misinterpretation of total drug concentration and response to antiarrhythmic drugs acutely, during convalescence and at discharge.