Infective endocarditis involving a presumably normal pulmonic valve.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Morganroth.
Explore the source record for details and available documents.
The pharmacokinetics of cibenzoline were evaluated in four young healthy volunteers who received ascending oral doses of 65, 97.5, 130, 162.5, 195, 227.5, and 260 mg separated by one week. Cibenzoline plasma concentrations exhibited an apparent biexponential decline following oral absorption. Maximum plasma concentrations and area under the plasma concentration-time curve increased in proportion to the dose. The mean elimination half-life among subjects was independent of dose and ranged from 7.3 to 8.7 hours. Oral clearance ranged from 380 to 575 ml/min and was also independent of dose. A single pharmacokinetic equation was used to adequately describe the plasma concentration data over the entire range of doses for each subject, indicating dose-proportional and linear pharmacokinetics.
To determine the usefulness of exercise cardiokymography (CKG) compared to thallium-201 perfusion scanning in the diagnosis of coronary artery disease (CAD), 179 patients with a mean age of 54 +/- 10 years (73% men) were studied. Previously documented CAD was present in 73 patients (41%); 13 (7%) were asymptomatic and 93 (53%) had chest pain syndrome. Exercise stress testing, CKG, and thallium-201 perfusion scanning were independently correlated with coronary angiographic data. Treadmill exercise stress test alone without CKG had a sensitivity of 68% and specificity of 62%. CKG showed a sensitivity of 76% and a specificity of 90%, and easily interpreted cardiokymograms were obtained in 78% of patients studied. Thallium-201 scans had a sensitivity of 79% and a specificity of 88%. However, when the CKG and treadmill exercise test results were concordant (both positive or both negative), the CKG exercise test had a sensitivity of 87% and specificity of 100%. Thus, when the CKG and exercise test results are concordant, the sensitivity and specificity are equal to or better than thallium-201 perfusion scanning for the prediction of CAD. Since CKG is an inexpensive and noninvasive test, its adjunctive use with routine exercise stress testing may be of great value.
Explore the source record for details and available documents.
The antiarrhythmic effect of nadolol, a long-acting, nonselective beta antagonist without intrinsic sympathomimetic or membrane-stabilizing properties, was evaluated in 36 patients with ventricular dysrhythmias as determined by three baseline 24-hour Holter recordings at a time when subjects were receiving placebo. Nadolol was administered once daily at a dose of 40 to 80 mg and increased at weekly intervals to a maximum daily dose of 640 mg. Thereafter the drug was stopped gradually and placebo was given again for a period of 2 weeks. Nadolol was effective in reducing premature ventricular contractions (PVCs) in 17 of 36 patients (48%), in reducing ventricular couplets in 24 of 27 patients (89%), and in reducing nonsustained runs of ventricular tachycardia in all 13 subjects. Serum nadolol levels obtained at dosages resulting in a 75% reduction in PVCs varied from 58 to 853 ng/ml. In the majority of the subjects studied, a nadolol dosage of 160 mg/day or less was effective for arrhythmia suppression.
Nadolol, a long-acting beta-adrenergic-blocking agent, was evaluated in 20 patients with chronic atrial fibrillation by means of a randomized, double-blind, crossover study. Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation (3 minutes, 1.75 mph, 10% grade). With placebo the group averaged a heart rate of 92 +/- 19 bpm, determined by 24 hours of ambulatory ECG recordings; this rate was significantly reduced to 73 +/- 16 bpm (p less than 0.001) with nadolol (mean dosage, 87 +/- 43 mg/day). During standardized exercise testing, heart rates increased to 153 +/- 26 bpm with placebo and to 111 +/- 24 bpm with nadolol (p less than 0.001), representing 65% and 52% increments, respectively. Digoxin blood levels averaged 0.8 +/- 0.5 ng/ml with placebo and were similar with nadolol (0.9 +/- 0.4; p = NS). Total exercise time on a modified Bruce treadmill protocol was 466 +/- 143 seconds with placebo and was significantly decreased by nadolol (380 +/- 143; p less than 0.01). During initial dose titration with nadolol, one patient was dropped from study for intolerable fatigue and one for worsened claudication. No patients were dropped from the double-blind treatment periods, although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue. We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment.
An 84-year-old female who previously underwent repair of an atrial septal defect had evidence of increased reflectiveness of the posterior tricuspid anulus in the apical four-chamber view and the right ventricular two-chamber view. In addition, the inferior vena cava was dilated and during contrast echocardiography, contrast echoes appeared during systole suggesting tricuspid regurgitation. Tricuspid annular calcification was confirmed by fluoroscopic examination. Tricuspid annular calcification is extremely rare and in the present series occurred in 1 of 80 patients with mitral annular calcification. Lateral resolution echoes from a calcified aortic valve and echoes originating from a calcified right coronary artery have to be distinguished from tricuspid annular calcification.
Explore the source record for details and available documents.
Conventional antiarrhythmic drugs are an important tool for the clinical cardiologist for the treatment of ventricular arrhythmias. Knowledge of the different properties of these drugs will help decrease the incidence of adverse effects and increase the frequency of successful therapy.
Tricuspid regurgitation is often not apparent on physical examination and several methods are now available to aid in this difficult assessment. Cardiac catheterization using right ventriculography, previously considered the diagnostic standard, has several limitations. Currently available noninvasive tools such as M-mode and two-dimensional echocardiography (with or without contrast), Doppler techniques and even radionuclide cardiologic imaging have added significantly to the precise assessment of the presence and severity of tricuspid regurgitation. This review examines the comparative use and limitations of these various techniques.
The relationship between plasma concentrations of cibenzoline and its antiarrhythmic effect was evaluated in patients receiving the drug orally as part of an ascending multiple dose efficacy and tolerance study. Twenty-five patients participated in a 3-day placebo period, 3 days of 32.5 mg cibenzoline every 6 hr, 3 days of 65 mg cibenzoline every 6 hr, 3 days of 81.25 mg cibenzoline every 6 hr, and 3 final placebo days. Arrhythmia frequency was monitored by 24-hr Holter monitoring and blood samples were drawn during and after dosing. Percent reduction in baseline premature ventricular complex (PVC) frequency for the 25 subjects demonstrated considerable interpatient variability in antiarrhythmic response. Cibenzoline plasma concentrations over 300 ng/ml were associated with some decrease in PVC frequency in virtually all cases. The relationship between plasma concentration and PVC frequency was studied more rigorously in eight of the 25 patients and that for ventricular couplet (VC) frequency was studied in six. For these analyses, PVC and VC frequency data were averaged over 6-hr intervals and plotted against trough cibenzoline concentrations. The data from each patient were fitted with a concentration-effect function (Hill equation) by means of least squares regression. With the exception of two extreme values, the concentration corresponding to 90% reduction in PVC frequency (C90) ranged from 215 to 405 ng/ml. In five of the six patients with arrhythmia in whom VC data were also evaluated, the individual C90 for VCs were considerably less than those for PVCs. The agreement between the observed concentration-response relationships and those predicted by curve-fitting the data suggests that the antiarrhythmic effect of cibenzoline is proportional to its plasma concentration, and that the Hill equation provides an accurate mathematic description of the concentration-response relationship.
Explore the source record for details and available documents.
The recognition of marked spontaneous variability in the frequency of ventricular ectopy has required the analysis of various statistical approaches to define appropriate guidelines for determining that a therapeutic agent, rather than spontaneous variability alone, is the cause of an observed reduction in VPC frequency. Analysis of variance or linear regression techniques have been applied to ambulatory ECG data obtained on different patient population groups. When similar patient groups are studied with comparable assumptions, then either of these statistical techniques provides similar guidelines to detect spontaneous variation as the cause of ventricular ectopic reduction. A 75% minimal reduction in VPC frequency should be required when comparing one 24-hour ambulatory monitoring period with another. The impact of spontaneous variability of ventricular ectopy on clinical trial designs is discussed, as is the categorization of various ambulatory ECG monitoring recorders and analysis systems.
The recognition that patients at high risk for sudden cardiac death can be identified raises our enthusiasm to eliminate some of these risk factors and thus our hope to prevent sudden cardiac death. Although this effect is yet to be shown in cooperative, well-controlled clinical trials, data exist to suggest that this result will be achieved. Thus, the use of antiarrhythmic agents in chronic ventricular ectopy, particularly in patients with left ventricular dysfunction, seems to be warranted, and new and more potent agents to be used for this end will be available in the future.
Explore the source record for details and available documents.
These conventional antiarrhythmic agents, plus tocainide, are important drugs for the treatment of ventricular arrhythmias. It is necessary to be familiar with their mechanism of action, pharmacokinetics, dosage, and adverse effects to properly use them in the treatment of ventricular arrhythmias.
The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind, randomized, crossover study. The heart rate in patients who received verapamil compared with placebo group was lower at rest (mean 69 +/- 13 versus 87 +/- 20 beats/min, p less than 0.01), as was the degree of tachycardia at the end of 3 minutes of a standardized exercise test (104 +/- 14 versus 136 +/- 23 beats/min, p less than 0.01). Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients, 320 mg/day in 6 patients, and 480 mg/day in 3 patients. Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study. Two patients were discontinued from the study because of adverse reactions. No clinically significant changes during verapamil therapy were observed on the electrocardiogram, chest roentgenogram, echocardiogram or in the laboratory evaluation. Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo (1.23 +/- 0.59 versus 0.85 +/- 0.46 ng/ml, p less than 0.01), but no patient had signs or symptoms of digitalis toxicity. Thus, oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia.
Explore the source record for details and available documents.