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Biomedical subjects

F I Marcus

Publications and source records attributed to F I Marcus.

At least 55 records · Page 3Linked to original sources
PubMed1994

Radiofrequency catheter ablation of accessory pathways: a contemporary review.

Catheter ablation techniques are now advocated as the first line of therapy for arrhythmias caused by accessory pathways (APs). The most common energy source is radiofrequency current, but technical characteristics vary. Several parameters can be used to determine the optimal target site: AP potential, AV time, atrial or ventricular insertion site, or unipolar morphology. Specific considerations are needed depending on AP location. Despite the different approaches described, there is no significant difference in the reported success rate, which is over 90%. However, the number of radiofrequency applications needed to achieve ablation appears to differ significantly, with median values from 3 to 8 reported. A combination of criteria related to both timing and direction of the activation wavefront or use of subthreshold stimulation could improve the accuracy of mapping. In patients with "resistant" APs, different changes in ablation technique must be considered during the procedure to achieve elimination of AP conduction. The incidence of complications in multicenter reports is close to 4%, with a recurrence rate of 8%. The long-term safety of catheter ablation requires further study.

Adolescent↗
PubMed1994

Resolution of pace mapping stimulus site separation using body surface potentials.

BACKGROUND: Several studies have related 12-lead ECG waveform during ventricular tachycardia to ECG waveform during ventricular pacing to identify ablation sites for therapy of ventricular tachycardia. QRS isopotential maps and QRS isointegral maps derived from body surface isopotential maps have also been correlated with left ventricular pacing sites with the same objective. The comparison process used is subjective and only semiquantitative. Improved accuracy of catheter placement may improve success rates of ablation therapy. METHODS AND RESULTS: This animal study was performed to determine the spatial resolution with which left ventricular pacing sites could be distinguished by body surface isopotential mapping. Potentials were recorded from 64 evenly spaced thoracic leads. Hexapolar or octapolar pacing catheters with 2-mm interelectrode spacing were placed percutaneously in the left ventricle in each of six dogs, and bipolar endocardial pacing was performed using each pair of adjacent electrodes. QRS isopotential maps of each pacing site for each catheter placement were cross-correlated by computer. Difference maps for each pair of pacing sites were calculated lead by lead and time instant by time instant, and root-mean-square voltage differences were calculated. Results indicated that correlation coefficients and root-mean-square error of voltage differences monotonically decrease and increase, respectively, with stimulus site separation. Both measures were significantly different (P < .05) for separations of 4 mm or more. CONCLUSIONS: A method of quantitative comparison of body surface potential maps can be used in normal hearts to localize ventricular pacing sites within a 4-mm range. The method may have utility in determining potential ablation sites for therapy of ventricular tachycardia or preexcitation syndromes.

Animals↗
PubMed1993

Detection and significance of myocardial ischemia in stable patients after recovery from an acute coronary event. Multicenter Myocardial Ischemia Research Group.

OBJECTIVE: To determine the clinical significance of silent and symptomatic myocardial ischemia detected by noninvasive testing in stable postcoronary patients. DESIGN: Cohort study with a mean 23-month follow-up. SETTING: Ambulatory outpatients after recent hospitalization for an acute coronary event. PATIENTS: Nine hundred thirty-six patients (76% male; mean age, 58 years) who were clinically stable 1 to 6 months after hospitalization for acute myocardial infarction or unstable angina. INTERVENTIONS: Noninvasive testing involved rest, ambulatory, and exercise electrocardiograms and stress thallium-201 scintigraphy. MAIN OUTCOME MEASURES: Cox regression analysis was used to evaluate the risk (hazard ratio) of first recurrent primary events (cardiac death, nonfatal infarction, or unstable angina) or restricted events (cardiac death or nonfatal infarction) associated with ischemic noninvasive test results. RESULTS: ST segment depression on the rest electrocardiogram was the only noninvasive test variable that identified a significantly increased risk (P = .05) for first recurrent primary events (hazard ratio; 95% confidence limits): rest electrocardiogram ST depression (1.5; 1.00, 2.25); ambulatory electrocardiogram ST depression (0.86; 0.49, 1.51); exercise electrocardiogram ST depression (1.13; 0.82, 1.56); and stress thallium-201 reversible defects (1.3; 0.96, 1.74). Test results were similar for first recurrent restricted events, and in patients with and without angina. Significantly increased risk (P < .05) was noted when exercise-induced ST depression occurred in patients who also had reduced exercise duration (hazard ratio, 3.4) or when reversible thallium-201 defects occurred in patients who also had increased lung uptake (hazard ratio, 2.8). Each high-risk subset made up less than 3% of the population and contained less than 6% of patients with first primary events. CONCLUSION: Detection of silent or symptomatic myocardial ischemia by non-invasive testing in stable patients 1 to 6 months after an acute coronary event is not useful in identifying patients at increased risk for subsequent coronary events.

Adult↗
PubMed1993

Digoxin is effective, but is it safe?

In the last 15 years several double-blind, placebo-controlled clinical trials have unequivocally shown that digitalis decreases symptoms of cardiac failure, results in a reduction in the need for hospitalization for treatment of congestive heart failure, and improves cardiac function. The major unresolved question concerning digitalis use is its safety. There are experimental data and clinical evidence that digitalis use may be associated with an increased mortality, particularly in the first year or two after an acute myocardial infarction. This increased mortality appears to be present even after adjustment for predictor covariants. This conclusion depends on the ability of statistical methods to account for differences in comorbidity. Since the question of digitalis safety remains after myocardial infarction, the physician should carefully examine the indications for administration of digitalis. More than the usual surveillance is required during chronic digitalis administration.

Cardiac Output, Low↗
PubMed1992

Superiority of a vertical sternal lead for detection of arrhythmias during ambulatory electrocardiographic monitoring.

In a preliminary study comparing 7 sets of bipolar leads with standard modified V1 and V5 leads, a vertical sternal lead system with the negative lead just below the suprasternal notch, and the positive lead over the xiphoid had the greatest P-wave area. In the current study, the vertical sternal and modified V1 leads were obtained simultaneously using 2-channel ambulatory electrocardiographic recorders in 50 consecutive patients undergoing diagnostic ambulatory electrocardiography for suspected arrhythmias. The vertical sternal lead provided tracings with a larger P-wave area compared with that of the modified V1 (0.58 +/- 0.44 vs 1.23 +/- 0.69 mm2; p less than 0.0001), and a greater QRS complex (9.23 +/- 4.16 vs 11.78 +/- 4.90 mm; p = 0.006). During premature atrial contractions and supraventricular tachycardia, P-wave visibility was significantly better in the sternal lead than in V1 (p less than 0.001). Furthermore, sternal lead tracings were superior with regard to overall quality and noise level. It is suggested that the vertical sternal lead replace the currently used modified V1 during ambulatory electrocardiographic monitoring. This lead system in conjunction with the standard modified V5 lead should be useful in the differential diagnosis of atrial arrhythmias.

Adolescent↗
PubMed1992

Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations.

The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure.

Animals↗
PubMed1992

Evaluation of electrocardiographic leads for detection of atrial activity (P wave) in ambulatory ECG monitoring: a pilot study.

The usual lead systems for ambulatory ECG monitoring (AECG) used in the evaluation of arrhythmias is a modified bipolar V-1 and V-5. A comparison of various lead systems to enhance the detection of atrial activity (p waves) has not been reported. We evaluated various surface lead systems in 12 subjects comparing p waves recorded at 20 mm/mV and 50 mm/sec. We compared p wave area, amplitude, and duration from modified bipolar V1 and V5 as well as seven nonstandard leads recorded on a AECG monitor. Of the seven nonstandard leads, a vertical sternal lead, with the negative pole just below the suprasternal notch and the positive pole at the xiphoid process, had the largest area (1.46 +/- 0.65 mm2), and also had a greater area than the standard V1 (0.88 +/- 0.45 mm) and V5 (1.06 +/- 0.49 mm2) lead system (P less than 0.01). We conclude that the bipolar vertical sternal lead system provides a larger p wave area than seven nonstandard bipolar lead systems and the two standard lead systems currently used in AECG monitoring. Replacement of the modified bipolar V1 lead with a vertical sternal lead should improve the recognition of atrial activity and, therefore, enhance the diagnosis of cardiac arrhythmias.

Adult↗
PubMed1992

Drug combinations and interactions with class III agents.

Drug combinations with class III antiarrhythmic agents have not been studied systematically. There are data indicating that enhanced efficacy as evaluated by electrophysiologic studies can be obtained by combining sotalol and a type Ia drug or amiodarone with low-dose beta-blocking drugs. Combining amiodarone with a type Ia or Ic drug or with a beta-blocking drug can slow the rate of ventricular tachycardia to make the ventricular tachycardia hemodynamically well tolerated. Pharmacokinetic drug interactions with amiodarone are extensive. Recently, it has been shown that hepatic metabolism of amiodarone can be induced to enhance the conversion of amiodarone to N-desethylamiodarone. The physiologic effect of this drug transformation is uncertain. There should be few pharmacokinetic drug interactions with sotalol because this drug is almost completely absorbed, does not bind to plasma proteins, and is excreted unchanged by the kidneys.

Amiodarone↗
PubMed1991

High-performance liquid chromatographic method for the quantitation of quinidine and selected quinidine metabolites.

A specific and sensitive assay for the separation and quantitation of quinidine, 3-hydroxyquinidine, quinidine-N-oxide, O-desmethylquinidine and dihydroquinidine is presented. The assay is shown to be sensitive to concentrations of 0.1 microgram/ml for all the above compounds when using a serum sample of 0.1 ml. The standard curve demonstrates linearity at concentrations from 0.1 to 5 micrograms/ml. The extraction procedure consists of adjusting the serum to an alkaline pH and extracting once with a mixture of methanol-dichloromethane (15:85). The organic extract is dried and the residue is solubilized in mobile phase. The chromatographic conditions are an isocratic delivery of the mobile phase 0.01 M K2HPO4-acetonitrile (96:4) through a C18 column at ambient temperature. Detection of the compounds of interest is by ultraviolet absorption at a wavelength of 210 nm. For each compound the inter-assay variation is less than 10% and the intra-assay variation is less than 15%. No interfering compounds were detected when a commercially prepared serum spiked with 28 commonly used therapeutic compounds was assayed by this method. The analytical method presented here for the isolation and quantitation of quinidine, several active metabolites, and dihydroquinidine has adequate sensitivity and specificity for monitoring the concentration of quinidine and quinidine metabolites in patient samples.

Chromatography, High Pressure Liquid↗
PubMed1991

Ventricular arrhythmias. When should they be suppressed?

Patients with asymptomatic ventricular premature complexes who do not have evidence of heart disease should not be treated with either class I or class III (Vaughan Williams) antiarrhythmic drugs. Patients who are symptomatic may be given beta blockers. In patients who have heart disease, a number of risk factors may play a part, and the decision regarding therapy is more difficult. However, symptomatic patients with either sustained or nonsustained ventricular tachycardia must be treated with antiarrhythmic agents. In some patients, implantation of an automatic defibrillator may be necessary.

Anti-Arrhythmia Agents↗
PubMed1991

Assessment of effects of a radiofrequency energy field and thermistor location in an electrode catheter on the accuracy of temperature measurement.

Accurate measurement of temperature at the interface of the delivery electrode and the tissue during transcatheter delivery of radiofrequency energy (RFE) for ablation would provide better control of lesion production. Electromagnetic energy fields can affect the accuracy of temperature measurement with thermistors. An electrode probe was fabricated with a thermistor and an optical sensor in the center of the delivery electrode. Simultaneous temperature measurements during RFE delivery to cardiac tissue in the 37 degrees C bath showed good agreement between the sensors, indicating that the RFE field did not cause errors in thermistor temperature measurements with the electrode probe used. A second electrode probe was designed to determine optimal thermistor location. It was constructed using two thermistors with identical temperature-resistance curves. One thermistor protruded through a hole in the side of the delivery electrode and was thermally isolated from it. The other thermistor was bonded to the inner surface of the electrode with heat conductive epoxy. The electrode was placed in contact with cardiac tissue in a 37 degrees C bath of flowing saline with the protruding thermistor centered in the area to be heated. Temperatures measured at steady state during RFE delivery with the protruding thermistor were consistently higher than those of the inner wall thermistor, ranging from 1.8 degrees C difference at 46 degrees C to 8.3 degrees C difference at 75 degrees C interface temperature. The thermistor must be in contact with the tissue and thermally isolated from the delivery electrode for accurate determination of electrode/tissue interface temperature.

Animals↗
PubMed1990

Steady-state interaction between amiodarone and phenytoin in normal subjects.

Amiodarone has been reported to increase phenytoin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction at steady-state. Pharmacokinetic parameters for phenytoin were determined after 14 days of oral phenytoin, 2 to 4 mg/kg/day, before and after oral amiodarone, 200 mg daily for 6 weeks in 7 healthy male subjects. During amiodarone therapy, area under the serum concentration time curve for phenytoin was increased from 208 +/- 82.8 (mean +/- standard deviation) to 292 +/- 108 mg.hr/liter (p = 0.015). Both the maximum and 24-hour phenytoin concentrations were increased from 10.75 +/- 3.75 and 6.67 +/- 3.51 micrograms/ml to 14.26 +/- 3.97 (p = 0.016) and 10.27 +/- 4.67 micrograms/ml (p = 0.012), respectively, during concomitant amiodarone treatment. Amiodarone caused a decrease in the oral clearance of phenytoin from 1.29 +/- 0.30 to 0.93 +/- 0.25 liters/hr (p = 0.002). These results were due to a reduction in phenytoin metabolism by amiodarone as evidenced by a decrease in the urinary excretion of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, 149 +/- 39.7 to 99.3 +/- 40.0 mg (p = 0.041) and no change in the unbound fraction of the total phenytoin concentration expressed as a percentage, 10.3 +/- 2.7 versus 10.7 +/- 2.1% (p = 0.28) during coadministration of amiodarone. The alterations in phenytoin pharmacokinetics suggest that steady-state doses of phenytoin of 2 to 4 mg/kg/day should be reduced at least 25% when amiodarone is concurrently administered. All dosage reductions should be guided by clinical and therapeutic drug monitoring.

Adult↗
PubMed1990

Age-related prognosis after acute myocardial infarction (the Multicenter Diltiazem Postinfarction Trial).

The basis for the excess mortality with age after acute myocardial infarction (AMI) is not clear, nor is it known whether the mode of death is altered with age. Age-related factors predictive of mortality and age-related mechanisms of the 333 deaths were examined in 2,466 patients who were enrolled in a placebo-controlled trial to determine the effect of diltiazem on mortality and reinfarction after AMI. There were 3 age groups with increasing mortality rates: ages 25 to 49 (n = 499), 50 to 64 (n = 1,228) and 65 to 75 years (n = 739). There was a significant age-related increase in the proportion of patients with baseline risk factors. These baseline characteristics did not differ by treatment (placebo vs diltiazem). However, multivariate survivorship analysis still identified age as an independent risk factor for cardiac death. The proportion of arrhythmic and myocardial failure deaths did not differ by treatment or age group.

Adult↗
PubMed1990

Effect of phenytoin on the clinical pharmacokinetics of amiodarone.

Five healthy male volunteers were given oral amiodarone hydrochloride, 200 mg per day for 6 1/2 weeks, to determine its effects on the pharmacokinetics of both intravenous and oral phenytoin. Predose amiodarone and N-desethylamiodarone serum concentrations were obtained weekly during weeks 2-6. Amiodarone serum concentrations (ASC) increased during weeks 2-4 and then decreased sharply during weeks 5-6 when oral phenytoin, 2-4 mg/kg/day, was co-administered. In addition, N-desethylamiodarone serum concentrations (DEASC) exceeded corresponding ASC during weeks 5-6 whereas during weeks 2-4, DEASC were less than ASC. Because of the long elimination half-life for amiodarone previously reported in healthy volunteers after single doses of amiodarone and the frequent administration of amiodarone associated with this half-life, a modified equation for a continuous infusion was used to describe each subject's ASC versus time data. Pre-phenytoin ASC were fitted to an appropriate function to predict ASC during weeks 5-6 assuming no interaction. Observed versus predicted ASC were compared for weeks 5 and 6. Observed ASC during weeks 5 and 6 were (mean +/- SD) 0.25 +/- 0.09 micrograms/mL and 0.19 +/- 0.07 micrograms/mL, respectively. Corresponding predicted ASC were 0.36 +/- 0.12 micrograms/mL (P = .011) and 0.38 +/- 0.13 micrograms/mL (P = .004). These represented percent differences of 32.2 +/- 12.5% and 49.3 +/- 5.6% for weeks 5 and 6, respectively. Assuming there were no changes in the bioavailability of amiodarone during continuous administration, these findings strongly suggest induction of amiodarone metabolism by phenytoin. The clinical significance of this interaction remains to be determined.

Administration, Oral↗