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Transitions among atrial fibrillation, atrial flutter, and sinus rhythm during procainamide infusion and vagal stimulation in dogs with sterile pericarditis.

The mechanism of atrial flutter and fibrillation induced by rapid pacing in 22 dogs with 3-day-old sterile pericarditis was investigated by computerized epicardial mapping of atrial activation before and after administration of agents known to modify atrial electrophysiologic properties: procainamide, isoproterenol, and electrical stimulation of the vagosympathetic trunks. Before the administration of any of these agents, a total of 30 episodes of sustained atrial flutter (greater than 1 min duration, monomorphic; regular cycle length, 127 +/- 12 ms, mean +/- SD) was induced in 15 out of 22 dogs and 9 episodes of unstable atrial flutter (duration, less than 1 min; cycle length, 129 +/- 34 ms; monomorphic, alternating with fibrillation) were induced in the remaining 7 preparations. In the latter, administration of procainamide transformed unstable atrial flutter and atrial fibrillation to sustained atrial flutter (cycle length, 142 +/- 33 ms; n = 9 episodes). During control atrial flutter, atrial maps displayed circus movement of excitation in the right atrial free wall with faster conduction parallel to the orientation of intra-atrial myocardial bundles. Vagal stimulation changed atrial flutter to atrial fibrillation in 32 of 73 trials; this was associated with acceleration of conduction in the lower right atrium, leading to fragmentation of the major wave front. Isoproterenol produced a 6-25% increase of the atrial rate in 6 out of 14 trials of atrial flutter and induced atrial fibrillation in 4. After procainamide, the reentrant pathway was lengthened and conduction was slowed further in the right atrium. Maps obtained during unstable atrial flutter showed incomplete circuits involving the right atrium. Following procainamide infusion, the area of functional dissociation or block was enlarged and a stable circus movement pattern, which was similar to the pattern seen in control atrial flutter, was established in the right atrium. We conclude that (1) the transitions among atrial fibrillation, atrial flutter, and sinus rhythm occur between different functional states of the same circus movement substratum primarily located in the lower right atrial free wall, and (2) the anisotropic conduction properties of the right atrium may contribute to these reentrant arrhythmias and may be potentiated by acute pericarditis.

Animals

Operations for atrial fibrillation.

Atrial fibrillation is the most common of all sustained cardiac arrhythmias, yet it has no effective medical or surgical therapy. During the past decade, multipoint computerized electrophysiological mapping systems were used to map both experimental and human atrial fibrillation. On the basis of these studies, a new surgical procedure was developed for atrial fibrillation. Between September 25, 1987, and May 1, 1991, this procedure was applied in 22 patients with either paroxysmal atrial flutter (n = 2), paroxysmal atrial fibrillation (n = 11), or chronic atrial fibrillation (n = 9) of 2 to 21 years' duration. All patients were refractory to all antiarrhythmic medications and each patient failed an average of 5.2 drugs preoperatively. There were no operative deaths and all perioperative morbidity resolved. All 22 patients have been cured of atrial fibrillation with surgery alone. One late isolated episode of atrial flutter occurred in a patient who is now receiving encainide. Preservation of atrial transport function has been documented in all of the patients postoperatively and all have experienced marked clinical improvement.

Adult

Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter.

The need for prophylactic anticoagulation to prevent embolism before direct current cardioversion is performed for atrial fibrillation or atrial flutter is controversial. To examine this issue further, a retrospective review was undertaken to assess the incidence of embolic complications after cardioversion. The review involved 454 elective direct current cardioversions performed for atrial fibrillation or atrial flutter over a 7 year period. The incidence rate of embolic complications was 1.32% (six patients); the complications ranged from minor visual disturbances to a fatal cerebrovascular event. All six patients had atrial fibrillation, and none had been on anticoagulant therapy (p = 0.026). The duration of atrial fibrillation was less than 1 week in five of the six patients who had embolic complications. Baseline characteristics of patients with a postcardioversion embolic event are compared with those of patients who did not have an embolic event. There was no difference in the prevalence of hypertension, diabetes mellitus or prior stroke between the two groups, and there was no difference in the number of patients who were postoperative or had poor left ventricular function. Left atrial size was similar between the two groups. No patient in the embolic group had valvular disease. No patient with atrial flutter had an embolic event regardless of anticoagulant status; therefore, anticoagulation is not recommended for patients with atrial flutter undergoing cardioversion. Prophylactic anticoagulation is pivotal in patients undergoing elective direct current cardioversion for atrial fibrillation, even those with atrial fibrillation of less than 1 week's duration.

Anticoagulants

Value of the atrial signal-averaged electrocardiogram in identifying patients with paroxysmal atrial fibrillation.

Atrial signal-averaged electrocardiogram was compared between 25 patients with paroxysmal atrial fibrillation and 20 healthy persons without atrial arrhythmias (control). The duration time of the high frequency (50-250 Hz) P wave was significantly (P less than 0.01) prolonged in the groups of patients with paroxysmal atrial fibrillation compared with the control group (116 +/- 16.4 versus 92 +/- 8.1 msec). The diagnostic value of the duration of the high frequency P wave for identifying patients with paroxysmal atrial fibrillation was 104 msec. Using this criterion, a sensitivity of 76% and a specificity of 90% were achieved. Our observation has shown that the atrial signal-averaged electrocardiogram is a useful technique for identifying patients with paroxysmal atrial fibrillation.

Adult

Metabolic studies following thoracotomy for lung cancer with particular reference to postoperative atrial fibrillation.

Atrial fibrillation has proved to be a frequent complication after thoracotomy for lung cancer. In order to study the possibility that metabolic changes are the trigger mechanism of these arrhythmias, free fatty acids (FFA), glycerol, triglycerides, serum insulin and glucose were determined pre- and postoperatively in patients both with and without this postoperative complication. In the primary series of patients, FFA were found to be increased immediately after the start of the atrial fibrillation, partly in relation to the morning values and partly to the 24-hour curve. This is a possible expression of an increased lipolysis in a causal relationship to the arrhythmia. In another series of patients, the degree of lypolysis was demonstrated using the glycerol values. With this method, no signs of increased lipolysis were found in connection with the onset of atrial fibrillation. Thus, changes in the lipoid metabolism were not found to be the trigger mechanism of the postoperative atrial fibrillation. Reduced values of serum insulin and glucose were not demonstrated either during the uncomplicated postoperative period or at the start of atrial fibrillation.

Atrial Fibrillation

Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter.

BACKGROUND: Diltiazem, a calcium channel blocker, has been shown to be safe and effective in the treatment of patients in atrial fibrillation and/or atrial flutter. However, there have been no pharmacokinetic/pharmacodynamic studies of diltiazem in these patients. METHODS AND RESULTS: The pharmacokinetics and pharmacodynamics of intravenous diltiazem were determined in 32 patients with atrial fibrillation or atrial flutter (mean +/- SD age, 66 +/- 7 years; mean baseline heart rate, 131 +/- 10 beats per minute) after 20 mg or 20 mg followed by 25-mg bolus doses and a 10 and 15 mg/hr infusion for 24 hours. After the 10 and 15 mg/hr infusions of diltiazem, mean +/- SD elimination half-life was 6.8 +/- 1.8 and 6.9 +/- 1.5 hours, volume of distribution was 411 +/- 151.8 and 299 +/- 70.8 I, and systemic clearance was 42 +/- 12.4 and 31 +/- 8.3 l/hr, respectively. Percentages of the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem to diltiazem were < 15% and < 10%, respectively. Thirty of 32 patients maintained response throughout the 24-hour infusion of diltiazem. Using a sigmoidal Emax pharmacodynamic model, a strong relation (mean +/- SD r2, 0.78 +/- 0.2) was observed between plasma diltiazem concentration and percent heart rate reduction. Mean +/- SD Emax (maximum percent reduction in heart rate from baseline) and EC50 (plasma diltiazem concentration that achieves half Emax) were 52 +/- 17% and 110 +/- 84 ng/ml, respectively. The model predicts that mean plasma diltiazem concentration of 79, 172, and 294 ng/ml are required to produce a 20%, 30%, and 40% reduction in heart rate, respectively. A relation between plasma diltiazem concentration and percent change in systolic blood pressure (SBP) or diastolic blood pressure (DBP) from baseline was not observed (mean +/- SD r2, SBP/DBP: 0.35 +/- 0.24/0.36 +/- 0.2). There were no untoward side effects observed. CONCLUSIONS: First, the pharmacokinetics of diltiazem in patients with atrial fibrillation or atrial flutter is nonlinear with an apparent dose-dependent decrease in systemic clearance with increasing infusion rate. Second, using a sigmoidal Emax model, there is a strong relation between plasma diltiazem concentration and percent heart rate reduction. Third, the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem are low and are not expected to contribute significantly to the pharmacodynamics of intravenous diltiazem in these patients.

Aged

The Maze procedure: a new treatment for atrial fibrillation.

Atrial fibrillation is a dysrhythmia with lethal complications afflicting thousands of people each year. Unfortunately, atrial fibrillation is frequently resistant to medical therapy and other nonsurgical treatments, such as cardioversion and catheter ablation. Past surgical procedures to correct the dysrhythmia have also proved ineffective. A surgical procedure has been developed in which multiple incisions are made in the atrium, creating an electrical maze. The maze procedure restores atrioventricular synchrony while simultaneously preventing macroreentry within the atria. It thereby eliminates the clinical sequelae often associated with atrial fibrillation and improves the quality of life for those patients refractory to current methods of treatment.

Aged

[Drug treatments of atrial fibrillation].

Atrial fibrillation is a daily cardiological problem which poses three types of questions, which, though old, are only partially mastered: anticoagulation, reduction and prevention of recurrence. It is a potent source of embolism. The risk is the greatest in patients with rheumatic valvular disease when the fibrillation is recent and when underlying cardiac disease is uncompensated. Long term anticoagulation is mandatory when the cause is rheumatic heart disease. In other pathologies, though anticoagulation has not been shown to reduce mortality, it significantly reduces the number of cerebrovascular accidents, including in the elderly and with low-dose vitamin K antagonist drugs. The efficacy of anticoagulation in preventing arterial embolism has not been established. Reduction of atrial fibrillation is not essential if the arrhythmia is well tolerated, chronic, especially in elderly patients and when several recurrences have occurred despite preventive therapy. In other cases, medical reduction is to be preferred to cardioversion if the fibrillation is recent and well tolerated. Of the oral and injectable preparations, amiodarone seems to be the drug with best benefit/risk ratio. Prevention of recurrence of fibrillation is unnecessary for many after a first episode, especially when idiopathic. In other cases, there are many available drugs but results are uncertain except in those observed in atrial fibrillation related to the autonomic nervous system. Strictly controlled and statistically exploitable studies show comparable efficacy of quinine and other Class I drugs. Beta-blockers are not very useful and the excellent long term results with amiodarone require confirmation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Efficacy and safety of intravenous diltiazem for treatment of atrial fibrillation and atrial flutter. The Diltiazem-Atrial Fibrillation/Flutter Study Group.

This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter. A double-blind, parallel, randomized, placebo-controlled protocol was used, and 6 large, urban hospitals, both university-affiliated and private, participated. The study involved 113 patients with atrial fibrillation or flutter, a ventricular rate greater than or equal to 120 beats/min and systolic blood pressure greater than or equal to 90 mm Hg without severe heart failure. The dose of intravenous diltiazem (or identical placebo) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective. If a patient did not respond, the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given. Of 56 patients, 42 (75%) randomized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg, for a total response rate of 52 of 56 patients (93%), whereas 7 of 57 patients (12%) responded to placebo (p less than 0.001). After the double-blind protocol, 49 of the 57 patients who received placebo were then given diltiazem; 47 of 49 responded, for an overall response rate of 99 of 105 patients (94%) with diltiazem. The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes. Side effects occurred in 14 patients, 7 of whom had asymptomatic hypotension not requiring intervention. Thus, intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter. Blood pressure decreased slightly. Side effects were mild.

Aged

The alternation between atrial flutter and atrial fibrillation.

Atrial fibrillation and atrial flutter share a common reentrant mechanism. However, the relationship between these arrhythmias has not been systemically studied to date. To evaluate the degree to which these arrhythmias may alternate, consecutive Holter monitor recordings which showed fibrillation or flutter in 96 patients were reviewed. One half of the patients were studied after open-heart surgery and the other half for varying indications. One quarter of the patients had atrial flutter in addition to fibrillation, and this alternation with flutter was significantly associated with the use of a type 1A antiarrhythmic drug (p = 0.007), but not with the use of digoxin or beta blockers (p = NS for both). Furthermore, this alternation with flutter was more common in the postoperative group (p = 0.01). A history of embolization was less common in patients who were in the postoperative group (p = 0.003) and patients who had flutter in addition to fibrillation (p = 0.05).

Adolescent

Relation between spontaneous atrial fibrillation and atrial vulnerability in patients with Wolff-Parkinson-White pattern.

An intracavitary electrophysiological study was carried out on 103 patients with Wolff-Parkinson-White (WPW), 23 symptomatic patients had documented episodes of atrial fibrillation, 54 symptomatic patients had atrioventricular reentrant tachycardias, and 26 asymptomatic. Patients were examined for the relation between spontaneous atrial fibrillation and atrial vulnerability, defined as the possibility to induce sustained (greater than 1 minute) episodes of atrial fibrillation with a stimulation protocol excluding atrial bursts. Atrail fibrillation induction was attempted by single and double atrial extrastimuli during pacing at two different cycle lengths and incremental atrial pacing. Sustained atrail fibrillation was induced in 65% of the patients with spontaneous atrial fibrillation, and in 13% of the symptomatic patients with documented episodes of atrioventricular reentrant tachycardias and in 15% of the asymptomatic patients (P less than 0.0005). Atrial vulnerability was higher in patients with spontaneous atrial fibrillation than in patients without this arrhythmia. No significant difference was observed between symptomatic without atrial fibrillation and asymptomatic patients.

Adult

Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter.

The effects of esmolol, an ultrashort-acting beta blocker, and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter, in a randomized, parallel, open-label study. Patients with either new onset (less than 48 hours, n = 31) or old onset (greater than 48 hours, n = 14) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol (n = 21) or verapamil (n = 24). Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm. The heart rate declined with esmolol from 139 to 100 beats/min (p less than 0.001) and with verapamil from 142 to 97 beats/min (p less than 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p less than 0.03). Mild hypotension was observed in both treatment groups. Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter. Moreover, conversion to sinus rhythm is significantly more likely with esmolol.

Adrenergic beta-Antagonists

Role of calcium antagonists for heart rate control in atrial fibrillation.

Atrial fibrillation is one of the most common symptomatic sustained arrhythmias seen in clinical practice. Many patients with atrial fibrillation and a ventricular response greater than 120 beats/min will experience cardiac symptoms. In the past, control of heart rate in these patients consisted of administration of intravenous digoxin, but this often proved to be ineffective or limited by toxicity. Recently, intravenous beta blockers such as esmolol have been used to slow the ventricular rate during atrial arrhythmias, but in some studies their use has been limited by hypotension. Alternatively, a bolus of an intravenous calcium antagonist, e.g., diltiazem or verapamil, may be administered to achieve acute slowing of the ventricular response. An intravenous bolus of diltiazem or verapamil may be effective, but use of either may be limited by its short duration of action and the inability to administer repeated boluses to tightly control or "fine tune" the heart rate. However, a new bolus plus maintenance infusion technique with diltiazem has shown promise in initial studies. It appears that in the future, continuous infusion techniques with intravenous calcium antagonists will be available that provide safe and effective sustained control of the ventricular response during atrial arrhythmias.

Atrial Fibrillation

Lidocaine in Wolff-Parkinson-White syndrome with atrial fibrillation.

Atrial fibrillation in the Wolff-Parkinson-White syndrome may be life-threatening because of the extremely rapid ventricular rates that can occur over the accessory pathway. An 18-year-old man with Wolff-Parkinson-White (type B) syndrome developed episodes of syncope due to atrial fibrillation. In studies during hospitalization the administration of lidocaine immediately slowed the ventricular response by abolishing antegrade conduction over the accessory pathway. The role of lidocaine and other antiarrhythmic drugs in the management of arrhythmias in the Wolff-Parkinson-White syndrome is discussed.

Adolescent

Verapamil in atrial fibrillation and atrial flutter.

A double-blind randomized study was performed to compare the efficacy of intravenous verapamil with saline in 28 patients with a rapid ventricular rate and atrial fibrillation or atrial flutter. Conversion of atrial fibrillation to sinus rhythm occurred in none of 14 patients after saline and in 3 of 20 patients (15%) 7 to 160 min after verapamil. The ventricular rate in atrial fibrillation was slowed greater than or equal to 15% in 2 of 14 patients (14%) by saline, in 17 of 20 patients (85%) by 1 dose of verapamil (p less than 0.001), and in 19 of 20 patients (95%) by 1 or 2 doses of verapamil (p less than 0.001). Conversion of atrial flutter to sinus rhythm occurred in none of 4 patients after saline and in 1 of 7 patients (14%) 105 min after verapamil. The ventricular rate in atrial flutter was slowed greater than or equal to 15% in none of 4 patients by saline, in 4 of 7 patients (57%) by 1 dose of verapamil, and in 7 of 7 patients (100%) by 1 or 2 doses of verapamil (p less than 0.001).

Adult

Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs.

One hundred nine patients with recurrent episodes of symptomatic atrial fibrillation or flutter, or both, who had failed one to five previous antiarrhythmic drug trials were treated with propafenone and, subsequently, sotalol if atrial fibrillation recurred. The clinical profile of the study group was as follows: age 63 +/- 13 years, left atrial anteroposterior dimension 4.4 +/- 0.9 cm and left ventricular ejection fraction 57 +/- 14%. Paroxysmal atrial fibrillation occurred in 56 patients (51%) and chronic atrial fibrillation occurred in 53 patients (49%). After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol. Life table estimates of the duration of freedom from atrial fibrillation were constructed for each drug trial. The percent of patients free of recurrent symptomatic arrhythmia at 6 months was 39% for propafenone and 50% for sotalol. The cumulative proportion of patients successfully treated with propafenone or sotalol, or both, by 6 months was 55% and remained relatively constant beyond that point. The incidence of intolerable side effects necessitating discontinuation of therapy ranged from 7% to 8%. Thus, despite previous unsuccessful drug trials, a substantial proportion of patients with recurrent symptomatic atrial fibrillation refractory to conventional therapy can be treated successfully and safely with newer antiarrhythmic drugs. Treatment failures tend to occur early in the course of follow-up, permitting easy identification of candidates for alternative therapeutic approaches.

Adult

[Value of echocardiography and amplified atrial vectorcardiography for selecting the methods of therapy and prevention of paroxysmal atrial fibrillation].

Atrial and left-ventricular myocardial activity was assessed in 85 coronary patients with paroxysmal atrial fibrillation. Their age varied between 43 and 88 years. The methods used included ECG, amplified atrial vectorcardiography after I. T. Akulinichev's schedule (amplification: 1 mv = 100 mm) and M-scan echocardiography. The comparison of these methods has substantiated criteria for the selection of differential treatment and preventive measures in these patients, on the basis of the prevailing type of atrial myocardial changes ("arrhythmic", "hemodynamic" or "combined" ones). A supportive treatment with cardiotonic agents is advisable in cases of the "hemodynamic" type with apparent signs of the overstrain (dilation) of the left atrium or both atria. In the "arrhythmic" variant, where conductivity, automatism and excitation disorders are predominant, antiarrhythmic agents (cordaron, quinidine, adrenoblockers) are indicated while the "combined" type calls for combined treatment with cardiotonic and antiarrhythmic agents.

Adult