Effects of oral propafenone on defibrillation and pacing thresholds in patients receiving implantable cardioverter-defibrillators. Propafenone Defibrillation Threshold Investigators.

OBJECTIVES: The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. BACKGROUND: Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. METHODS: After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. RESULTS: There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. CONCLUSIONS: Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.

Acute spontaneous failure of a porcine aortic valve.

The performance of the porcine bioprosthetic heart valve has been well characterized in terms of thrombogenicity, susceptibility to infection, and hemodynamic characteristics. There has been some concern about the frequency and mechanism of late dysfunction of this valve. To date, cases of valve failure have been progressive and gradual. We saw a case of acute, catastrophic, spontaneous failure of a porcine bioprosthetic heart valve. We suggest that in the differential diagnosis of acute aortic insufficiency acute spontaneous failure of a porcine aortic prosthesis be included.

Superior vena cava syndrome. Its association with indwelling balloon-tipped pulmonary artery catheters.

The placement of flow-directed pulmonary artery catheters has become a routine procedure in hospitals throughout the country. There have been scattered reports of complications associated with their placement, but in general, if it is done under proper conditions, it is associated with low morbidity and mortality. Recently, there have been questions raised regarding the thrombogenicity of these catheters. We report three cases of superior vena cava syndrome associated with the use of indwelling pulmonary artery catheters that we have encountered and a review of experience of others.

Serum estrogen levels in men with acute myocardial infarction.

Serum estradiol and serum estrone levels were assessed in 29 men in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospitalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p less than 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiol's ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand.

Outcome after cardiac arrest during acute myocardial infarction.

A community-wide study of acute myocardial infarction (AMI) was conducted in all 16 acute-care general hospitals in the Worcester, Massachusetts, metropolitan area during the years 1975, 1978, 1981 and 1984. The in-hospital and long-term prognoses of 667 patients with AMI complicated by cardiac arrest (CA) was compared with that of 2,596 AMI patients without CA. The incidence of CA complicating AMI was similar (21%) during each of the 4 study years. Among patients with AMI who had CA, 36% had CA within the first day of hospitalization and 48% within the first 2 days. The in-hospital case-fatality rate was much higher for AMI patients with CA (78%) than for those without CA (4%) (p less than 0.001). For patients discharged alive from the hospital, a trend toward a higher mortality rate was seen at 1 and 2 years after hospital discharge for patients with CA; however, long-term survival rates were not significantly different between AMI patients with and without CA. When time of occurrence of CA relative to in-hospital survival was examined, patients with early CA (within 1 day or within 2 days of hospital admission) had a significantly greater in-hospital survival (39% and 34%) than did those with late CA (after 1 day or after 2 days) (13% and 12%). Similarly, patients discharged from the hospital after early CA had a significantly better chance of long-term survival than patients discharged after late CA.

Electrophysiologic predictors of long-term clinical outcome with amiodarone for refractory ventricular tachycardia secondary to coronary artery disease.

Fifty-four patients with a previous myocardial infarction and drug-refractory symptomatic ventricular tachycardia (VT) were treated with amiodarone on a long-term basis (range 6 to 54 months, mean 26) irrespective of the results of programmed ventricular stimulation, which was performed after high-dose oral amiodarone loading for more than 4 weeks. VT was rendered noninducible in 6 of 54 patients (11%) taking oral amiodarone. During a mean follow-up of 32 months, these 6 patients remained free of VT or sudden cardiac death. Forty-eight patients (89%) continued to have VT inducible by programmed ventricular stimulation. However, they could be separated into 2 groups: VT-modified (20 patients) and VT-unchanged (28 patients). In the VT-modified group, the induced VT with amiodarone was slowed or rendered nonsustained, and only 3 of 20 (15%) patients during a mean follow-up of 23 months had well tolerated VT recurrences. In the VT-unchanged group, 16 of 28 patients (57%) had recurrences of VT or ventricular fibrillation during a mean follow-up of 24 months. Sudden cardiac death occurred in 6 of these 16 patients. Thus, programmed ventricular stimulation in patients with VT taking long-term amiodarone may have prognostic implications.

Amiodarone for refractory atrial fibrillation.

Atrial fibrillation (AF) is a difficult arrhythmia to manage with antiarrhythmic agents. Amiodarone is highly effective in restoring and maintaining normal sinus rhythm in patients with AF. However, the mechanism and predictors of efficacy for amiodarone in treating AF have not been adequately addressed. Various measures of success or failure of amiodarone therapy were examined in 68 patients who had paroxysmal or chronic, established AF refractory to conventional antiarrhythmic agents. The patients were 25 to 75 years old (mean 59) and mean follow-up was 21 months (range 3 to 56). Maintenance amiodarone dosages were 200 to 400 mg/day. Overall, amiodarone therapy was effective long term in 54 of the 68 patients (79%). Left atrial diameter, age, gender and origin of AF were not helpful in predicting success or failure of amiodarone therapy. The presence of chronic AF for longer than 1 year was an adverse factor in maintaining normal sinus rhythm (p = 0.007), although the success rate even in this group was relatively high (57%). Thirty-five percent of the patients had adverse effects, which precluded long-term therapy with amiodarone in 10%.

The relation of the kinetics of pirmenol to its antiarrhythmic efficacy.

In a single-blind study the multiple oral dose kinetics of pirmenol were related to its efficacy in eight patients with frequent (mean, 631; range, 167-1374 beats/hour) premature ventricular contractions (PVC). Oral pirmenol was started at 100 mg bid for 48 hours and increased to 150 mg bid in six patients to obtain more than 70% suppression of PVC counts. Efficacy was achieved without side effects. Pirmenol decreased heart rate but not PR interval, QRS duration, or QTc interval. Peak plasma levels after the first 100-mg dose occurred at 1 to 3 hours and ranged from 0.6 to 1.9 micrograms/mL. Plasma elimination half-life ranged from 9.7 to 31 hours (mean, 18.3). From 67.4 to 171.3 mg pirmenol (mean, 102.3 mg) were recovered in the urine in 48 hours after the last dose. Cumulative excretion in divided urine collections was consistent with a mean elimination half-life of 15 to 20 hours. The pharmacokinetics of pirmenol support oral twice-daily administration. The minimum PVC suppressing plasma level is between 0.5 and 1.5 micrograms/mL.

Chemistry, pharmacology, antiarrhythmic efficacy and adverse effects of tocainide hydrochloride, an orally active structural analog of lidocaine.

Tocainide is an orally effective antiarrhythmic agent, structurally and pharmacologically similar to lidocaine. It appears to be free of marked negative hemodynamic or electrophysiologic effects in patients with heart disease, despite a high frequency of minor and often transient central nervous system and gastrointestinal side effects. Tocainide is effective in suppressing ventricular arrhythmias in a variety of settings. This agent may be a useful addition to our antiarrhythmic armamentarium.

Temporary cardiac pacing: modes, evaluation of function, equipment, and trouble shooting.

Artificial cardiac pacing has become a sophisticated therapeutic and diagnostic tool in the management of arrhythmic cardiac emergencies. Major innovations have occurred in the last three decades since the advent of temporary pacing, and today, pacing can be effected "physiologically" in both chambers. This has been the result of improved venous access techniques, technologic improvements in electrode design, and the development of sophisticated external pulse generators. It has become clear that ventricular pacing alone does not improve the hemodynamic derangement consequent upon ventricular bradycardia and AV dyssynchrony. The restoration of AV synchrony either by atrial pacing preceding ventricular events or by ventricular pacing at a defined AV delay following a sensed atrial event (P wave) can often reverse the hemodynamic derangement and result in both extension of life and more rapid reversal of the clinical compromise in certain cases of acute heart block. Temporary pacing has always been used for bradyarrhythmias, but more recently, antitachycardia pacing is being utilized increasingly in the acute care setting.

Clinical pharmacokinetics of amiodarone.

This article attempts to provide an overview of the present knowledge of the pharmacokinetics of amiodarone and how this relates to the clinical usage of oral amiodarone. It is apparent that wide gaps still exist in our knowledge of amiodarone's pharmacokinetics in humans and the best fit for the observations following a single oral dose and chronic dosing is that of a three compartment model with body tissues acting as a large reservoir of the drug; hence the very large volume of distribution (greater than 5001). It remains unclear as to exactly when steady state is achieved except that full clinical efficacy for ventricular tachyarrhythmias may take several weeks following high oral dosing (about 15g). The drug's bioavailability is modest (approximately 40%) and excretion is minimal via the hepatic route. It is extensively metabolised in all tissues to desethylamiodarone, whose antiarrhythmic properties remain to be elucidated. This metabolite is found to parallel amiodarone's concentration in serum but its concentration is variable in tissues. The liver shows the highest, and body fat the lowest concentrations of desethylamiodarone. The minimal effective serum concentration has not been established with certainty, and the unique pharmacokinetics of this agent has made it difficult to perform dose-response studies, especially in life threatening arrhythmias. Similarly, the toxic serum concentrations have not been established though it appears that a higher incidence of side effects occurs if serum concentrations exceed 2.5 mg/l during chronic (steady state) therapy.

Chronic tocainide therapy for refractory high-grade ventricular arrhythmias.

Tocainide, an oral analog of lidocaine, was evaluated as a long-term antiarrhythmic agent in 21 patients with symptomatic complex ventricular ectopic activity (10 with hemodynamically significant ventricular tachycardia) refractory to currently available antiarrhythmics singly, and in combination for periods of 3 days to 35 months (mean 13.6 months). Tocainide appeared to be an effective and safe agent for the control of these refractory symptomatic ventricular arrhythmias in 14 of the 21 patients (66%). Minor central nervous system and gastrointestinal side effects were present in most of the patients, usually early on in therapy, and only precluded long-term use in 2 patients. Furthermore, lidocaine responsiveness was a good predictor of tocainide effectiveness in this group of patients. Tocainide precipitated atrioventricular (A-V) block in one patient with pre-existing A-V nodal disease; two patients developed a skin rash while on tocainide therapy. These two patients had previously developed lupus-like syndromes and skin rashes while on procainamide. The ANA titers had been falling in these two patients while on tocainide, and in one of these patients with true systemic lupus erythematosus, rechallenge with tocainide failed to produce skin rash. Tocainide's long plasma half-life and high oral bioavailability permit an 8-h regime. We conclude that tocainide is an effective, safe antiarrhythmic agent with tolerable side effects.

Prevention of AV nodal reentry tachycardia by oral amiodarone: an alternative mechanism of action.

A 73-year-old man was noted to have atrioventricular (AV) nodal reentry tachycardia, which was induced during programmed electrical stimulation. After 1 month of oral amiodarone therapy, AV nodal reentry tachycardia was prevented by the prolongation of atrial refractoriness and not by direct action on the AV node itself.

Antiarrhythmic agents and proarrhythmia.

The Vaughn Williams classification divides antiarrhythmic agents into four groups according to their effects on various ion channels. Class I agents block sodium channels and are subdivided into three groups. The use of class Ia agents is gradually on the decline, secondary to lack of a favorable risk/benefit ratio. Class Ib agents include lidocaine, which is extensively used for the acute treatment of ventricular tachyarrhythmias. Class Ic drugs are not advisable for patients with structural cardiac abnormalities secondary to a high risk of proarrhythmia. They are mainly used for supraventricular tachyarrhythmias. beta blockers form class II. Class III agents, such as amiodarone and sotalol, prolong action potential duration and repolarization and are among the most widely used antiarrhythmics. They are the subject of active research, and newer agents are being developed. Calcium-channel blockers are grouped under class IV. Digoxin and adenosine have unique antiarrhythmic properties, which can be useful in the management of selected patients. All antiarrhythmic drugs have the potential to provoke arrhythmias and, therefore, should be used with caution. The risk of proarrhythmia is increased in patients with abnormal cardiac substrate, with electrolyte abnormalities, and during drug initiation. Correction of electrolyte imbalance and prevention of bradycardia while the drug is metabolized and/or excreted are the cornerstones of proarrhythmia management.

Electrophysiologic and clinical factors influencing response to class IA antiarrhythmic agents in patients with inducible sustained monomorphic ventricular tachycardia.

Clinical and electrophysiologic data from 51 consecutive patients with sustained monomorphic ventricular tachycardia inducible during programmed ventricular stimulation were evaluated to determine what variables predict the response to intravenous class IA antiarrhythmic agents. All patients received acute drug testing in the electrophysiologic laboratory with either intravenous procainamide or intravenous quinidine. Ventricular tachycardia suppression was achieved in 9 out of 51 patients (18%). The age, gender, left ventricular ejection fraction, baseline right ventricular effective refractory period, baseline HV interval, and baseline ventricular tachycardia cycle length were not predictive of ventricular tachycardia suppression with intravenous procainamide or quinidine during programmed ventricular stimulation. The degree of prolongation of the right ventricular effective refractory period after drug administration did not predict success or failure to suppress inducible ventricular tachycardia. The degree of prolongation of the HV interval was also not predictive. In addition, the degree of prolongation of the right ventricular effective refractory period or the HV interval did not predict the change in the ventricular tachycardia cycle length after drug administration in patients who remained inducible. These data indicate that the response to class IA antiarrhythmic agents in patients with inducible sustained monomorphic ventricular tachycardia cannot be predicted on the basis of various clinical and electrophysiologic parameters.

Sudden death in idiopathic dilated cardiomyopathy: role of ventricular arrhythmias.

Sudden cardiac death (SCD) is associated with idiopathic congestive cardiomyopathy (IDCM) and most commonly is due to ventricular tachyarrhythmias. The recurrence rate of SCD in the absence of specific therapy is thought to be around 20%-30% per year. Asymptomatic and symptomatic ventricular arrhythmias are common in patients with IDCM and the direct causal link of such arrhythmias with SCD in IDCM patients remains to be established. Furthermore, therapy directed at suppressing these ventricular arrhythmias has not been shown to decrease the incidence of SCD. Various approaches such as ambulatory monitoring, electrophysiological testing, signal-averaged electrocardiogram, and hemodynamics have met with variable success in identifying patients prone to SCD. Additionally, therapeutic approaches to prevent SCD in IDCM patients have produced equivocal results. This article reviews the published studies addressing the causal link of ventricular arrhythmias to sudden death in patients with IDCM and the attempts to decrease the incidence of sudden.