Inpatient versus outpatient initiation of antiarrhythmic drug therapy for patients with supraventricular tachycardia

In-hospital initiation of antiarrhythmic drug therapy is often recommended to observe the effects of the drug and monitor for possible adverse reactions, especially proarrhythmia. However, the actual risk of proarrhythmia in patients undergoing treatment for supraventricular tachyarrhythmias is not well defined. While patients with ventricular tachycardia or ventricular fibrillation most often have underlying structural heart disease, this is not true for many patients with supraventricular tachycardia. It is therefore necessary to define more precisely which patients with supraventricular tachycardia are at risk for ventricular proarrhythmia and sudden cardiac death. An indepth analysis was conducted of 162 patients from 51 published reports of ventricular proarrhythmic events in patients treated for supraventricular tachycardia. Heart disease of various etiologies was present in 96% of patients. Proarrhythmia occurred most commonly with quinidine (72% of cases), and torsade de pointes was the most frequent proarrhythmic event (54%). More than half of all proarrhythmic events occurred within the first 3 days of initiating therapy or soon after increasing the dose of chronic drug therapy. Information was scant regarding the time to occurrence of ventricular proarrhythmia with flecainide and propafenone. With flecainide, nine cases were reported at varying times after initiation of therapy, from in-hospital to 8 months. Two cases of proarrhythmia with propafenone occurred at Day 10 and at 2 years. Because of the low frequency of proarrhythmia, in-hospital initiation of antiarrhythmic drug therapy may not be cost-effective. It is recommended when the effects of the drug on the arrhythmia must be monitored, or when initiating treatment or increasing the drug dose in patients with structural heart disease. These include patients with structural heart disease in whom quinidine, disopyramide, procainamide, amiodarone, or sotalol are being used. Observation should extend at least 2 to 3 days after sinus rhythm is restored.     

Safety considerations in the pharmacological management of atrial fibrillation

The pharmacological management of atrial fibrillation (AF) requires careful consideration from a safety perspective. This article focuses primarily on maintenance therapy using antiarrhythmic drugs (AADs). The foremost safety issue for AADs is the propensity of class IA and III agents to cause torsade de pointes arrhythmias. Class IA drugs, particularly quinidine, can induce torsade de pointes at low or subtherapeutic doses, but higher doses are not necessarily associated with an increased incidence. 'Pure' class III drugs such as dofetilide induce torsade de pointes in a dose-related manner, but some class III agents with more complex actions such as amiodarone have a markedly lower potential to cause this arrhythmia. The risk of torsade de pointes precludes the use of class IA and 'pure' class III agents in patients with left ventricular hypertrophy and bradycardia. Class IC agents may cause sustained monomorphic ventricular tachycardias and are generally precluded in ischaemic and structural heart disease. Advanced heart failure patients may be treated with amiodarone or dofetilide, but most other AADs are unsuitable. The most important extracardiac toxicities occurring with AADs are those of amiodarone. Drug interactions are a significant safety issue in the management of AF, including pharmacokinetic interactions in which plasma levels of the AAD are raised - increasing the risk of proarrhythmia - and concomitant use of drugs that prolong the QT interval. Notwithstanding these considerations, most patients with AF can be considered for rhythm control, provided there is adequate pre-treatment assessment and protocols for initiation, dosing and monitoring are followed with care.     

Detailed analysis of 24 hour ambulatory electrocardiographic recordings during ventricular fibrillation or torsade de pointes

Although the terminal cardiac rhythm is often well documented in many cases of sudden cardiac death, the antecedent or premonitory arrhythmias are usually not retrievable. The ambulatory electrocardiographic recordings of 12 patients who sustained ventricular fibrillation or torsade de pointes while wearing a long-term electrocardiographic monitor were analyzed in detail. A printout of the entire electrocardiographic recording was made and hand counts of ventricular arrhythmias were correlated with heart rate, QTc interval, RR interval preceding ventricular fibrillation or torsade de pointes and (RR')/QT initiating ventricular fibrillation or torsade de pointes. Common ambulatory electrocardiographic features in these 12 patients experiencing ventricular fibrillation or torsade de pointes included: 1) a period of high density of increasingly frequent or complex ventricular arrhythmias, or both, preceding ventricular fibrillation or torsade de pointes (11 patients); 2) R on T beats frequently initiating ventricular fibrillation or torsade de pointes (9 patients); and 3) repolarization abnormalities present for several hours before ventricular fibrillation or torsade de pointes (7 patients). No consistent relation between the RR and RR' interval initiating ventricular fibrillation or torsade de pointes was found; no consistent alteration in heart rate occurred before ventricular fibrillation or torsade de pointes. Thus, ventricular arrhythmias leading to sudden death in an ambulatory population do not occur in isolation but are preceded by a period of increased ventricular ectopic activity. Future guidelines for assessment of antiarrhythmic drug efficacy should include an evaluation of a drug's impact not only on ectopic beat frequency but also on arrhythmia density.     

Sotalol: A new β-adrenergic blocker for ventricular arrhythmias

Sotalol is a water-soluble, nonselective, β-adrenergic blocker that was recently approved in oral form in the United States for the treatment of ventricular arrhythmias that are judged to be life-threatening. As a β-blocker, sotalol is unique in having additional class-III antiarrhythmic activity. It is still not resolved whether sotalol is more effective than other β-blockers in managing arrhythmias, but there are suggestions that it might possess greater antiarrhythmic and life-protecting activities than other types of antiarrhythmic drugs. The drug is well tolerated, but, because of its electrophysiologic activity, there is a small risk of proarrhythmia, specifically the development of polymorphic ventricular tachycardia and torsade de pointes.     

Clinical,electrocardiographic and follow-up observations in patients having ventricular fibrillation during holter monitoring: Role of quinidine therapy

Ventricular fibrillation occurred during Holter electrocardiographic monitoring in 5 of 3,307 consecutive patients. All five patients had Holter studies for evaluation of antiarrhythmic drug therapy; their ages ranged from 51 to 65 years. No patient had acute myocardlal infarction; all had congestive heart failure and severe left ventricular dysfunction. One patient had ischemic and four had nonischemic cardiomyopathy. All patients had recently begun treatment with oral quinidine and had plasma quinidine levels of 1.24 to 5.18 μg/ml. The Holter monitoring revealed that all had a long Q-T interval and that ventricular fibrillation began during frequent ventricular premature beats and was immediately preceded by ventricular tachycardia of the torsade de pointes type. The coupling interval of the ventricular premature beats initiating torsade de pointes was late (440 to 720 ms) and followed long preceding cycles (840 to 1920 ms). Ventricular fibrillation resolved spontaneously in two patients, but two of the remaining three patients died despite attempted cardiopulmonary resuscitation.It is concluded that (1) left ventricular dysfunction, chronic ventricular arrhythmias and initiation of quinidine therapy were the common findings in these patients; (2) a long Q-T interval, late coupled ventricular premature beats and long preceding cycles facilitate initiation of ventricular fibrillation in quinidine-treated patients; and (3) direct on-line monitoring should be utilized in the management of these patients.     

Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care

Quinidine therapy is one of the most common causes of the acquired long QT syndrome and torsade de pointes. In reviewing clinical data in 24 patients with the quinidine-associated long QT syndrome, 20 of whom had torsade de pointes, we have delineated several heretofore unreported or underemphasized features. (1) This adverse drug reaction occurred either in patients who were being treated for frequent nonsustained ventricular arrhythmias or for atrial fibrillation or flutter. (2) In patients being treated for atrial fibrillation, torsade de pointes occurred only after conversion to sinus rhythm. (3) Although most patients developed the syndrome within days of starting quinidine, four had torsade de pointes during long-term quinidine therapy, usually in association with hypokalemia. (4) Because of the large experience with this entity at our institution, we have been able to estimate the risk as at least 1.5% per year. (5) Twenty of the 24 patients had at least one major, easily identifiable, associated risk factor including serum potassium below 3.5 mEq/L (four); serum potassium between 3.5 and 3.9 mEq/L (nine); high-grade atrioventricular block (four); and marked underlying, (unrecognized) QT prolongation (two). Plasma quinidine concentrations were low, being at or below the lower limit of the therapeutic range in half of patients. The ECG features typically included absence of marked QRS widening, marked QT prolongation (by definition), and a stereotypic series of cycle length changes just prior to the onset of torsade de pointes. Torsade de pointes started after the T wave of a markedly prolonged QT interval that followed a cycle that had been markedly prolonged (usually by a post ectopic pause).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation

Fourteen patients with established atrial fibrillation (longer than three months) that was refractory to treatment were studied to compare the clinical and electrophysiological effects of amiodarone and bepridil. All patients initially received bepridil for three weeks (200-600 mg/day), followed by amiodarone for two to three months (100-400 mg/day). Bepridil seemed to be slightly more effective than amiodarone in converting the fibrillation to sinus rhythm (nine of fourteen compared with four of ten). The ventricular response in atrial fibrillation was equally well controlled by bepridil and amiodarone, both at rest and during exercise. Bepridil was associated with the development of ventricular arrhythmias in eight of fourteen patients; two had torsade de pointes, which in one degenerated into fatal ventricular fibrillation. These arrhythmias seemed to be associated with bepridil induced prolongation of the QTc interval. No ventricular arrhythmias were seen during amiodarone treatment. Although bepridil seems to be an effective antiarrhythmic agent for the management of atrial fibrillation, its arrhythmogenic actions make it unsuitable for this purpose.     

A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation.

Fourteen patients with established atrial fibrillation (longer than three months) that was refractory to treatment were studied to compare the clinical and electrophysiological effects of amiodarone and bepridil. All patients initially received bepridil for three weeks (200-600 mg/day), followed by amiodarone for two to three months (100-400 mg/day). Bepridil seemed to be slightly more effective than amiodarone in converting the fibrillation to sinus rhythm (nine of fourteen compared with four of ten). The ventricular response in atrial fibrillation was equally well controlled by bepridil and amiodarone, both at rest and during exercise. Bepridil was associated with the development of ventricular arrhythmias in eight of fourteen patients; two had torsade de pointes, which in one degenerated into fatal ventricular fibrillation. These arrhythmias seemed to be associated with bepridil induced prolongation of the QTc interval. No ventricular arrhythmias were seen during amiodarone treatment. Although bepridil seems to be an effective antiarrhythmic agent for the management of atrial fibrillation, its arrhythmogenic actions make it unsuitable for this purpose.     

Proarrhythmia with Class III Antiarrhythmic Drugs: Definition, Electrophysiologic Mechanisms, Incidence, Predisposing Factors, and Clinical Implications

Proarrhythmia with Class III Antiarrhythmic Agents. Antiarrhythmic drugs can and do induce unexpected and sometimes fatal reactions by either producing new symptomatic arrhythmias or by aggravating existing arrhythmias. The definition of proarrhythmia has changed since controlled clinical studies showed a dichotomy between arrhythmia suppression and mortality. The nature of proarrhythmia reactions is linked to the electrophysiologic effects of various antiarrhythmic drugs. Whereas Class I agents without accompanying effects on repolarization generally produce ventricular tachycardia (often incessant) or fibrillation. Class III agents typically produce torsades de pointes that may deteriorate into ventricular fibrillation. The precise mechanism of torsades de pointes is not fully elucidated, although early afterdepolarization and increases in spatial or temporal dispersion of repolarization are likely possibilities. Proarrhythmic risk is lowest for amiodarone and is probably related to the drug's complex electrophysiologic profile. The incidence of torsades with sotalol increases with dose and the baseline values of the QT interval; the incidence with d-sotalol and other pure Class III agents remains unclear. Prospective, randomized, placebo-controlled studies to evaluate this are under way. The fact that d-sotalol increases mortality in postinfarction patients suggests that it may possibly be a common property of most, if not all, pure Class III compounds. The ongoing clinical trials with various Class III agents are likely to provide the critical information on this important therapeutic issue.     

Torsade de pointes induced by ajmaline

Ajmaline, a reserpine derivative, is an effective class I antiarrhythmic agent. Herein we report two cases of ajmaline-induced abnormal QT prolongation accompanied by polymorphic ventricular tachycardia of the torsade de pointes type. Since ajmaline is increasingly used for the acute termination of wide complex tachycardia and as a diagnostic tool after syncope and in patients with idiopathic ventricular tachyarrhythmias, our observations suggest that caution should be exercised with regard to the effects of the drug on the QT interval and its potency to induce proarrhythmia of the torsade de pointes type.     

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND. Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS. Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS. An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.     

Amiodarone in patients with previous drug-mediated torsade de pointes. Long-term safety and efficacy

The safety and efficacy of long-term amiodarone therapy were examined in 12 patients who had previously developed torsade de pointes as a complication of previous antiarrhythmic therapy. The QTc intervals were determined at the time of torsade de pointes (570 +/- 40 ms), after 7 days of amiodarone loading (490 +/- 70 ms), and after 3 months of chronic amiodarone administration (580 +/- 80 ms). Compared to a drug-free control period, QTc was significantly prolonged (P less than 0.05) at the time of torsade de pointes, after amiodarone loading, and after 3 months of amiodarone therapy. The QTc intervals at the time of torsade de pointes and after chronic amiodarone treatment were not significantly different. At 16 +/- 7 months of follow-up, all patients remained free of subsequent torsade de pointes, syncope, or sudden death. In addition, 5 of 6 patients with a history of sustained ventricular tachycardia remained free from arrhythmic recurrence despite persistence of inducible ventricular tachycardia during programmed stimulation studies done before discharge. We conclude that amiodarone can often be used safely and effectively in patients who have previously had an episode of drug-mediated torsade de pointes. Amiodarone-induced QTc prolongation, even when marked, does not predict recurrent torsade de pointes. These observations also suggest that the propensity for a drug to produce this arrhythmia is dependent on other electrophysiologic effects in addition to its ability to simply lengthen repolarization.     

Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy

BACKGROUND: Ibutilide is a class III drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsade de pointes. Amiodarone also prolongs the QT interval but rarely causes torsade de pointes. There are no studies in which the concomitant use of the 2 agents was examined. The purpose of the present study was to assess the efficacy and safety of cardioversion with combination therapy in patients with atrial fibrillation or flutter. METHODS AND RESULTS: The study included 70 patients who were treated with long-term oral amiodarone and were referred for elective cardioversion of atrial fibrillation (57 of 70, 81%) or flutter (13 of 70, 19%). Patients were taking amiodarone (153+/-259 days, mean+/-SD) and were administered 2 mg intravenous ibutilide. Left ventricular ejection fraction was measured with echocardiography. The QT intervals were measured on 12-lead ECG. Fifty-five patients (79%) had structural heart disease. Patients were in arrhythmia for 196+/-508 days before cardioversion, with a left ventricular ejection fraction of 50+/-11%. In patients with atrial fibrillation, 22 (39%) of 57 and 7 (54%) of 13 patients with flutter converted within 30 minutes of infusion. Thirty-nine patients who did not convert after ibutilide were treated with electrical cardioversion, and 35 (90%) of 39 patients were successfully converted. The QT intervals were further prolonged after ibutilide for the group from 371+/-61 to 479+/-92 ms (P:<0.001). There was 1 episode of nonsustained torsade de pointes (1 of 70, 1.4%) after ibutilide. CONCLUSIONS: The use of ibutilide converted 54% of patients with atrial flutter and 39% of patients with atrial fibrillation who were treated with long-term amiodarone. Despite QT-interval prolongation after ibutilide, only 1 episode of torsade de pointes occurred. Our observations suggest that combination therapy may be a useful cardioversion method for chronic atrial fibrillation or flutter.     

Acquired long QT syndrome with torsade de pointes in a patient with primary hypothyroidism

A case of 78 year-old woman with primary hypothyroidism and atrial fibrillation treated with sotalol, complicated with cardiac arrest due to ventricular fibrillation (VF) and torsade de pointes (TdP) is presented. The QT interval was prolonged to 660 msec. Episodes of polymorphic ventricular tachycardia and VF recurred. Lidocaine, tosylate bretylate and betabloker successfully eliminated VF but short-lasting episodes of TdP were still present. Increased doses of hormonal substitution with thyroid hormones successfully eliminated malignant ventricular arrhythmias and normalised QT interval to 430 msec.     

Optimal management with Class I and Class III antiarrhythmic drugs should be done in the outpatient setting: protagonist

It has been suggested that patients be admitted for the initiation of Class I and Class III antiarrhythmic drugs to avoid serious proarrhythmic consequences. The most clinically significant proarrhythmic response to Class IC agents is likely due to an interaction with acute ischemia, and hospitalization for initiation of drug therapy has little predictive or preventive value. Amiodarone has a low risk of proarrhythmia, and any proarrhythmic reactions are generally delayed. Class IA and Class III antiarrhythmic drugs cause acquired long QT syndrome arrhythmias, which can occur soon after initiation of therapy; however, only about half of the arrhythmic events occur within 3 days of initiation of therapy. It could be argued that all patients should be hospitalized to begin Class IA or Class III drugs; however, this approach has a low yield and is extremely expensive. An alternative is to use Class IA and Class III drugs for patients at low risk of torsades de pointes (e.g., males without heart failure, ventricular tachyarrhythmias, or active coronary disease), in whom hospitalization for drug initiation is not warranted. Higher risk patients are probably better treated with other agents, such as Class IC drugs or amiodarone for women without organic heart disease and amiodarone for patients with heart failure, a history of ventricular tachycardia, or active coronary disease. When a Class IA or Class III drug is required for patient with an increased risk of torsades de pointes, hospital admission for drug initiation may be indicated.     

Amiodarone-associated "torsade de pointes". Relevance of concomitant cardiovascular medication in a patient with atrial fibrillation and structural heart disease

A 69 year old female with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation suffered from occipital apoplexy. Under treatment with amiodarone 600 mg daily and concomitant medication with beta-acetyldigoxine (0.1 mg daily) and bisoprolole (1.25 mg daily), significant QT-prolongation (max. 700 ms; QTc: 614 ms) could be documented. Out of normofrequent sinus rhythm but as well out of bradycardia, the patient developed repetitive short-lasting "torsade de pointes" tachycardias (320 bpm) which terminated spontaneously. Serum electrolytes, plasma levels of digoxine (1.76 ng/ml) and amiodarone (1.9 mcg/ml) were within therapeutic range. This case report is the first to describe induction of amiodarone-associated "torsade de pointes" tachycardia during concomitant beta-blocker and digitalis medication in a patient with atrial fibrillation and structural heart disease. This points towards an elevated risk for proarrhythmia under this triple therapy.     

Iatrogenic torsade de pointes induced by thioridazine]

Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis. Traditionally, torsade de pointes has been described in association with a congenital or acquired (including drug and metabolic) causes of QT prolongation. Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. For the treatment of torsade de pointes, the conventional antiarrhythmic drugs cannot be relied on, cardiac pacing should be instituted as soon as possible; however, as this technique may not always be immediately available, isoproterenol infusion may be the first-choice treatment. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. This report describes a case of thioridazine-induced torsade de pointes treated efficaciously with magnesium sulphate and overdrive right ventricular pacing.     

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required?: yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications

Objectives. We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation.Background. The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related.Methods. The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation.Results. Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 ± 2.5 (mean ± SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022).Conclusions. Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.     

Antiarrhythmic drug initiation in patients with atrial fibrillation

Antiarrhythmic drugs remain the mainstay of treatment of atrial fibrillation, but their potential proarrhythmic effects hamper their optimal use. Drug-induced tachyarrhythmias (ventricular tachycardia or atrial tachyarrhythmias with rapid ventricular response) are life-threatening and often cause syncope. Because these events tend to cluster shortly after drug initiation, it is common practice to routinely hospitalize patients for drug initiation under continuous electrocardiographic surveillance. The low incidence of serious proarrhythmia makes the cost-effectiveness of this practice controversial. Torsades de pointes, in particular, can be predicted by the presence of one or more of the following risk factors: female gender, structural heart disease, prolonged baseline QT interval, bradycardia, hypokalemia, previous proarrhythmic responses, and higher drug plasma levels. Proarrhythmia induced by class IC agents is seen almost exclusively in patients with structural heart disease and ventricular dysfunction. A variety of monitoring devices permit electrocardiographic monitoring of patients in the outpatient setting. Efficient clinical pathways for the safe initiation of antiarrhythmic drugs in patients with atrial fibrillation do not require universal hospital admission. In patients without structural heart disease, outpatient initiation of most antiarrhythmic drugs appears safe. In patients with significant structural heart disease, class IC drugs are contraindicated, and most other drugs should be initiated in the hospital under continuous monitoring. The incidence of severe proarrhythmia is very low when loading doses of amiodarone of 600 mg/d or less are given to outpatients with structural heart disease.     

Dofetilide: a new class III antiarrhythmic agent

Dofetilide is a new, pure class III antiarrhythmic agent that prolongs the refractory period and action potential duration without having beta-blocking or calcium channel-blocking properties, making it unique among established class III agents. Dofetilide is effective in converting atrial and ventricular arrhythmias, and in maintaining sinus rhythm after cardioversion. Interestingly, it is more effective in converting atrial flutter than atrial fibrillation. It appears to be safe in patients with left ventricular dysfunction and postmyocardial infarction. In small studies, intravenous dofetilide was superior to flecainide, procainamide and amiodarone in converting atrial fibrillation and flutter. Dofetilide can be administered orally or intravenously with no significant effect on heart rate or blood pressure, but it can prolong QT interval and cause torsade de pointes in 3% to 4% of patients receiving it intravenously and in 0.8% to 1.5% of patients receiving it orally. So far, it is recommended that therapy be initiated in hospital under electrocardiogram monitoring for at least two days, with particular care to avoid torsade de pointes in high risk patients such as women, and those with bradycardia, hypokalemia, hypomagnesia and renal dysfunction. Studies have failed to show any extracardiac side effects.