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Biomedical subjects

F I Marcus

Publications and source records attributed to F I Marcus.

At least 73 records · Page 4Linked to original sources

Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects.

Previous reports have suggested an interaction between propafenone and digoxin. We investigated the pharmacokinetics of IV digoxin when given alone (Phase I), after pretreatment with propafenone 150 mg every 8 hours for seven days (Phase II), and after propafenone 300 mg every 8 hours for 7 days (Phase III). The total body clearance of digoxin during Phase I was 2.45 ml/min/kg and was 2.17 ml/min/kg during Phase II (NS) and decreased to 1.92 ml/min/kg during Phase III (P less than 0.05). The renal clearance and half-life of digoxin were not significantly altered by propafenone. There was a trend towards a decrease in the volume of distribution of digoxin from 9.43 L/kg in Phase I, to 9.33 L/kg in Phase II, and 8.02 L/kg in Phase III. Similarly there was a trend towards a decreased nonrenal clearance of digoxin from 1.21 ml/min/kg during Phase I to 1.01 ml/min/kg during Phase II and to 0.75 ml/min/kg during Phase III. The changes in volume of distribution and nonrenal clearance parallel each other resulting in no change in the elimination half-life of digoxin. It is postulated that the mechanism of this interaction is due to decreases in the volume of distribution and nonrenal elimination of digoxin by propafenone. The degree of this interaction was related to the dose of propafenone. The magnitude of this interaction may be greater in patients and, thus, may require a reduction in the digoxin dose.

Adult↗

The use of digitalis for the treatment of congestive heart failure: a tale of its decline and resurrection.

The decline of the use of digitalis for the treatment of congestive heart failure was due to the introduction of oral diuretic therapy, the recognition of the frequency of digitalis induced arrhythmias and the uncontrolled observations that digitalis could frequently be withdrawn from patients with a history of heart failure without recurrence of heart failure. Subsequently, it has been well documented that digitalis has chronic beneficial hemodynamic effects in patients with chronic congestive heart failure. Moreover, digitalis has been shown to improve hemodynamics when added to other drugs including diuretics, ACE inhibitors and vasodilators. It is concluded that digitalis is a mild inotropic agent that is still a primary drug for the treatment of mild to moderate acute or chronic left ventricular failure.

Digitalis Glycosides↗

Pharmacokinetic interaction between intravenous phenytoin and amiodarone in healthy volunteers.

To determine the mechanism of the amiodarone-phenytoin interaction, seven healthy male subjects were given intravenous phenytoin, 5 mg/kg, before (phase I) and after (phase II) 3 weeks of oral amiodarone, 200 mg/day. Serum AUC increased from 245 +/- 37.6 to 342 +/- 87.3 mg.hr/L (p = 0.007); area under the first moment curve increased from 5666 +/- 1003 to 11,632 +/- 4198 mg.hr2/L (p = 0.008); the time-averaged total body clearance decreased from 1.57 +/- 0.3 to 1.17 +/- 0.33 L/hr (p = 0.0004); and the apparent elimination half-life increased from 16.1 +/- 1.32 to 22.6 +/- 3.8 hours (p = 0.001) for phenytoin during phase II. The volume of distribution at steady state and the unbound fraction for phenytoin remained unchanged. However, the formation of p-hydroxyphenytoin as a function of serum phenytoin concentration decreased during phase II. These findings suggest that amiodarone inhibits phenytoin metabolism. These observations also suggest that phenytoin doses will need to be reduced when coadministered with amiodarone. The magnitude of this reduction is difficult to predict because of the saturable pharmacokinetics of phenytoin, and therapeutic monitoring is recommended if amiodarone is added to the phenytoin regimen.

Administration, Oral↗

Long-term follow-up in patients with arrhythmogenic right ventricular disease.

Follow-up was obtained in 33 of 35 patients with arrhythmogenic right ventricular disease (ARVD) from three centers, one in France, and two in the United States. The majority of patients are living but require antiarrhythmic drug therapy. Analysis of syncope as a prognostic factor for arrhythmic death in this series, as well as in patients with ARVD reported in the literature, suggests a more favourable long-term prognosis in those patients who did not have a history of syncope. ARVD may be due to a variety of pathological entities and the prognosis of patients who have different aetiologies may well be distinct from one another.

Adult↗

The effect of electrode design on the efficiency of delivery of radiofrequency energy to cardiac tissue in vitro.

Four types of electrodes were studied with respect to efficiency of delivery of radiofrequency energy (RFE) and characteristics of the lesions produced in dog ventricular muscle in vitro. An imbeddable needle electrode was found to be the most efficient of the four types studied, with a lesion volume/energy-delivered ratio of 1.10 mm3/joule at an optimum power level of 2.8 watts and power density at the electrode surface of 0.45 watt/mm2. Lesion volume was linearly related to energy delivered at all power levels used below a power density of 0.64 watt/mm2, at and above which tissue impedance increased abruptly. The electrode catheter typically used for RFE ablations was the least efficient at 0.15 mm3/joule and a power density at the electrode surface of 0.50 watt/mm2 at 6.27 watts. masking 2/3 of the electrode surface with electrically insulating epoxy caused the RFE current to be directed into the tissue, resulting in a threefold increase in efficiency (0.46 mm3/joule) at less than half the power (2.79 watts). A flat, thermally insulated electrode with larger (10 mm2) contact area approached the efficiency of the imbedded electrode with a ratio of 0.69 mm3/joule at a low power density of 0.19 watt/mm2 and 1.85 watt power level. Characteristics of an "ideal" electrode for RFE lesion production in cardiac tissue are discussed.

Animals↗

Physician utilization of laboratory procedures to monitor outpatients with congestive heart failure.

Little is known about how different types of physicians use laboratory procedures in the management of outpatients with congestive heart failure. We therefore analyzed data from a national survey of randomly selected general practitioners, internists, and cardiologists to assess their management of outpatients with New York Heart Association class II congestive heart failure. Most of the 2704 respondents (90%) scheduled office visits between two and four months apart. Body weight, serum electrolytes, and chest roentgenograms were followed regularly by 98% or more of respondents, at median intervals of one to two months, three to five months, and 12 to 17 months, respectively. Serum digoxin levels in patients taking digoxin were followed by 90% of respondents at a median interval of 12 months. Echocardiography, radionuclide ventriculography, and exercise testing were used by fewer respondents (81%, 61%, and 61%, respectively), each at a median interval of 18 months or longer. Cardiologists were significantly more likely to follow patients using either echocardiography, radionuclide ventriculography, or exercise testing. The estimated yearly cost of following a class II congestive heart failure outpatient varied nearly fourfold from the lowest quartile of physicians ($303) to the highest ($1167). Cardiologists were disproportionately represented among the high-cost users. In addition, physicians who were younger or who practiced in an urban setting were significantly more likely to be high-cost users. Thus, simple laboratory tests were used most frequently to follow patients with heart failure, but differences in use of more expensive tests led to large differences in cost. Test use for similar patients is affected by characteristics of both the physician and practice setting.

Ambulatory Care↗

The care of elderly patients with cardiovascular disease.

Cardiovascular disease is a major clinical problem in the elderly, with coronary heart disease the most frequent cause of death and with hypertension present in as many as 50% of these patients. The cardiovascular manifestations of aging must be differentiated from those due to disease. There are clinical manifestations and responses to therapy in the elderly that differ from those in younger patients. The extent of diagnostic and therapeutic procedures undertaken should be based on the patient's physiologic age, the presence and severity of concomitant diseases, mental status and cognitive ability, and the patient's expectations from medical care. Preventive approaches are also warranted.

Age Factors↗

Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction.

A prospective study to determine prognostic factors for risk stratification in 867 patients surviving the coronary care unit phase of acute myocardial infarction (AMI) is reported. During a 48-month follow-up, 144 patients (17%) died. The deaths were examined for the chronology, cause, mechanism, location and presence of myocardial ischemia in the terminal event. A classification previously proposed by Hinkle and Thaler was used to define the mechanism of cardiac death and the presence of ischemia. There were 113 deaths due to coronary atherosclerotic coronary artery disease, including 5 due to complications of coronary artery bypass graft surgery. Of the remaining 108 of these deaths, 74% were classified as due to an arrhythmic mechanism and 26% as myocardial failure. Of the deaths due to an arrhythmia or to myocardial failure, 56 (52%) occurred out of hospital. The ratio of arrhythmic: myocardial failure deaths was not different for the patients who died within 3 months after the index AMI compared with later deaths. Sudden death (less than or equal to 1 hour of new symptoms) was strongly associated with arrhythmic death but 32 (54%) of patients who died greater than 1 hour after the onset of symptoms were also classified as having an arrhythmic cause of death. Previously described risk factors, including an ejection fraction less than 0.40 and greater than or equal to 10 ventricular premature complexes/hour, were independent predictors of mortality but did not differentially predict the mechanism of cardiac death. Evidence of myocardial ischemia before the terminal event was found in about 50 (60%) patients whose deaths were witnessed and who died from an arrhythmia or myocardial failure.

Coronary Disease↗

Transient heart block associated with head trauma.

Atrioventricular nodal block is a rare consequence of head trauma. We report a case of a 63-year-old male with coronary artery disease who sustained a skull fracture. Twelve hours later the cardiac monitor recorded an episode of high-grade atrioventricular block with a ventricular escape rhythm. Subsequent electrophysiologic evaluation revealed no abnormality of atrioventricular nodal conduction nor of intraventricular conduction. Atrioventricular block after head trauma may be caused by enhanced vagal tone.

Creatine Kinase↗

Enhanced antiarrhythmic efficacy of propafenone when used in combination with procainamide or quinidine.

This study evaluated the efficacy and safety of combining propafenone with procainamide or quinidine for treating ventricular arrhythmias in patients in whom procainamide or quinidine therapy alone failed to suppress arrhythmias. In 30 patients, the addition of propafenone resulted in a significant reduction of premature ventricular contraction (PVC) frequency compared to drug-free baseline (406 PVC/hr vs 33, p less than 0.001) and to procainamide or quinidine monotherapy (211 PVC/hr vs 27, p less than 0.01). Propafenone alone was also more effective than either procainamide or quinidine and resulted in significant suppression of PVC compared to the drug-free state (406 PVC/hr vs 38, p less than 0.001). However, higher propafenone doses were necessary during monotherapy as compared to propafenone therapy combined with procainamide or quinidine (730 mg/day vs 480 mg/day, p less than 0.001). Of the 30 patients, 22 required an increase in propafenone dose during monotherapy as compared to combination therapy. Thus, propafenone is an effective antiarrhythmic agent when used in combination with type IA antiarrhythmic drugs. With these combinations, lower doses of propafenone can be utilized effectively than with propafenone alone.

Adult↗

Closed chest catheter desiccation of the atrioventricular junction using radiofrequency energy--a new method of catheter ablation.

Closed chest catheter ablation of the atrioventricular (AV) junction has been performed with direct current or laser energy. The effect of 750 kHz radiofrequency energy on ablation of the AV junction was evaluated in 13 dogs. The radiofrequency energy was generated from an electrosurgical generator in the bipolar mode. The radiofrequency output was delivered between two distal electrodes (bipolar ablation) in eight dogs, and between the distal electrode and an external patch electrode (unipolar ablation) in another five dogs at varying power (watts) but with a constant pulse duration of 10 seconds. Complete AV block was achieved in 11 dogs and second degree AV block in 2. During the 4 to 7 day follow-up period, complete AV block persisted in 9 of the 11 dogs with initial complete heart block. The other two had return of AV conduction; one had persistent 2:1 AV block and the other had persistent first degree AV block. Of the two dogs with initial second degree AV block, one developed complete AV block, the other had resumption of 1:1 AV conduction with a normal PR interval. Energy was delivered in 1 to 13 applications per dog. One hundred to 700 J per application was delivered with bipolar ablation and 10 to 100 J with unipolar ablation. There was no damage to the catheter unless the catheter was repeatedly used in excess of 1,500 J of total energy. Ventricular arrhythmias were not observed. Pathologic examination showed well delineated coagulation necrosis at the AV junction without surrounding hemorrhage or mural thrombus. Microscopic findings consisted of necrosis with cell infiltration in the periphery of necrosis. Most injuries involved the AV node, the approaches to the AV node and the penetrating bundle. In conclusion, catheter ablation of the AV junction with radiofrequency energy is safe. It can effectively induce discrete areas of necrosis and produce various degrees of AV block. In addition, ablation by radiofrequency energy has distinct advantages as compared with catheter ablation with direct current or laser energy.

Animals↗

Atenolol for ventricular ectopy: a dose-response study.

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.

Adult↗

Electrophysiologic and histologic observations of chronic atrioventricular block induced by closed-chest catheter desiccation with radiofrequency energy.

Direct-current or laser energy has been used to induce atrioventricular (AV) block, but certain complications associated with this type of energy have been reported. We have previously documented that radiofrequency (RF) energy can effectively and safely induce acute AV block in closed-chest dogs during the 4-7 days of follow-up. This study was undertaken to determine if the ablation was permanent and to define the chronic pathology and site of AV block. Complete AV block was successfully achieved in four dogs immediately after ablation with a bipolar "standard" RF output (750 kHz) delivered between the tip electrode of a standard 7F USCI catheter and an external patch electrode on the left lateral chest wall. During 2 months of follow-up, three dogs had persistent complete AV block with a stable escape rhythm; the other had persistent 2:1 AV block. Repeat His bundle recordings were performed at 2 months prior to sacrifice of the dogs. Supra-His AV block was noted in two dogs; His bundle potential could not be recorded in another two. Histologically, the damaged area was well delineated. In all animals, the AV node and, in some dogs, part of the His bundle were completely replaced by granulation tissue and/or cartilage. There was fatty infiltration and also chronic inflammatory cells around the lesions. Neither perforation, hemorrhage nor vacuolation was seen in the adjacent area. Thrombus was not present. It is concluded that RF energy can effectively achieve chronic AV block and produce well-circumscribed pathological lesions.

Animals↗

Endocardial catheter ablation for refractory ventricular tachycardia associated with coronary artery disease.

Percutaneous endocardial electrode catheter ablation using stored direct current (DC) electrical energy was performed in five patients with recurrent ventricular tachycardia (VT) refractory to many antiarrhythmic drugs, including amiodarone. All had prior myocardial infarction and poor left ventricular function with ejection fractions ranging from 20% to 40%. Endocardial catheter and pace mappings were used to localize the earliest site of activation during VT. Under general anesthesia, two to six shocks with 200 to 300 joules DC energy per shock were delivered to the localized sites. Immediate complications included ventricular fibrillation in one patient, transient QRS complex widening in two patients, transient complete AV block with persistent first-degree AV block in one patient, and transient asystole in two patients. None had inducible VT immediately following ablation, or 4 to 6 days later; none had evidence of intracardiac clot by two-dimensional (2D) echocardiography on the third to fifth day. Peak creatine kinase ranged from 189 to 1610 IU/L with 9% to 18% MB fraction. During a follow-up of 6 to 30 months, three patients had no recurrence of VT. Two patients had recurrent VT with a slower rate, which was controlled with antiarrhythmic drugs. None had worsening of congestive heart failure. Two patients died of nonarrhythmic causes. We conclude that nonsurgical endocardial ablation of VT with an electrode catheter is effective for the treatment of refractory VT in selected patients with coronary artery disease.

Aged↗

Ethmozine for ventricular premature complexes.

Twenty patients with an average of more than 30 ventricular premature complexes (VPCs) per hour were treated with ethmozine. Eighteen had either not responded or had adverse reactions to at least 1 other antiarrhythmic drug. Patients were treated with 200 to 300 mg 3 times daily (8.25 to 11.7 mg/kg) and were followed for up to 6 months. Three patients were withdrawn from ethmozine therapy because of unwanted effects before evaluation of efficacy. One of these patients had sustained ventricular tachycardia (VT) after a loading dose of ethmozine. Eleven of the remaining 17 patients (65%) experienced more than a 75% reduction in ventricular ectopic activity. Six patients had a smaller or no decrease in VPC frequency. Eleven of 16 patients (68%) with paired VPCs had a more than 90% reduction in paired VPC frequency. Eleven of 13 patients (84%) with VT events of 3 beats or more had more than a 90% reduction in VT events. Of the 11 patients in whom a more than 75% reduction in VPC frequency occurred, 1 patient died suddenly after 133 days of effective drug therapy. Three patients discontinued ethmozine therapy for reasons not related to the drug. Of the 6 patients in whom there was less than a 75% reduction in VPC frequency, 2 patients discontinued treatment, 1 patient because of hyperanxiety and 1 because of drug-related left anterior hemiblock. Ethmozine lengthened PR and QRS intervals but not the JT interval. Thus, ethmozine is effective and clinically useful for suppression of frequency VPCs in 50% (10 of 20 patients) of a selected population.

Aged↗