eMedicine Specialties > Emergency Medicine > Cardiovascular
Atrial Fibrillation: Treatment & Medication
Updated: Jul 15, 2009
- Overview
- Differential Diagnoses & Workup
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Treatment
Prehospital Care
- Care of hemodynamically unstable patients is guided by ACLS protocols, including direct current (DC) cardioversion.
- Symptomatic patients may benefit from intravenous (IV) rate-controlling agents, either calcium-channel blockers or beta-adrenergic blockers.
Emergency Department Care
Immediate interventions – ABCs
- Patients placed on cardiac monitor, O2, and ABCs are being assessed, ECG, IV access
- Unstable patients require immediate DC cardioversion.8
- Hypotension
- Decompensated CHF
- Ongoing ischemia or infarction
- These initial interventions occur simultaneously by the team of physicians and nurses taking care of the patient.
- In most circumstances, the patient is stable but has an elevated ventricular response and will require rate-controlling medications, with a heart rate goal of under 100.
- If there is another clinical condition driving the tachycardia, such as fever, infection, or dehydration, then efforts at temperature control and restoration of normovolemia will aid in controlling the tachycardia.
- Consideration of anticoagulation based upon patient risk factors may also begin in the emergency department.
Cardioversion11
Cardioversion can be pharmacologic based or electrical.
Anticoagulation and cardioversion may be indicated. Since there is a risk of thrombus formation and fragmentation, patients in atrial fibrillation for greater than 48 hours should receive therapeutic anticoagulation (INR 2-3 range) for 3 weeks prior to cardioversion. Alternatively, these patients can undergo heparinization, and TEE, and cardioversion if no thrombus is detected. In each case, anticoagulation needs to be continued for an additional 4 weeks.
Electrical cardioversion12
- DC cardioversion is the treatment of choice in the unstable patient with atrial fibrillation. Cardioversion is indicated in patients with first time atrial fibrillation or in patients with paroxysmal atrial fibrillation.
- Since atrial fibrillation begets atrial fibrillation, one may delay or prevent permanent atrial fibrillation by decreasing the overall time spent in atrial fibrillation in these early clinical stages.
- There is little utility in cardioverting stable patients with permanent atrial fibrillation, and the goal in this group is rate control.
- Placement of pads or paddle positions include anterior-lateral (ventricular apex and right infraclavicular) and anterior-posterior (sternum and left scapular), with at least one study suggesting increased efficacy with the anterior-posterior method.
- Biphasic waveforms are proved to convert atrial fibrillation at lower energies and higher rates than monophasic wave forms.
- Strategies include dose escalation (70, 120, 150, 170J for biphasic) or (100, 200, 300, 360J for monophasic) versus beginning with single high energy/ highest success rate for single shock delivered.
- Patients who are stable and/or awake and can tolerate sedation should be pretreated, with typical regimens involving midazolam, fentanyl, and propofol.
- Cardioversion of patients with implanted pacemakers and defibrillator devices is safe when appropriate precautions are taken. Keeping the cardioversion pads in an AP orientation ensures that the shocks are not directly over the generator. Alteration in pacer programmed data has been reported, as well as heart block and elevated enzymes if the current gets conducted through a pacer lead.
- Stunning of the atria and stasis can occur after cardioversion, and this can lead to thrombus formation even though the patient is in sinus rhythm. Therefore, patients would undergo anticoagulation for several weeks afterwards.
- Risks of cardioversion
- Risks with sedation
- Risk of thromboembolism (<1% with anticoagulation)
- Postcardioversion arrhythmias
Pharmacologic cardioversion is selected for patients who are symptomatic, who have had a short duration atrial fibrillation, or as an adjunct in patients who have failed electrical cardioversion.
Alboni et al studied outpatient treatment of atrial fibrillation with a “pill-in-the-pocket” approach in 268 patients with little or no structural heart disease presenting to the ED with symptomatic AF.13 Out of hospital self-administration of either flecainide 300 mg or propafenone 600 mg (weight based dosages if >70 kg) was evaluated. This treatment was successful in terminating AF in 94% of episodes (mean time to symptom resolution of 133 minutes).
Rate control
In most instances, patients presenting to the ED have preexisting atrial fibrillation and a rapid ventricular response. These individuals may already be on beta-blockers or calcium channel blockers, and initial attempts at rate control should be initiated with same class medications given intravenously, trying to avoid mixing classes of nodal blocking agents.
- Extreme care must be taken in patients with preexcitation syndrome and atrial fibrillation. Blocking the AV node in some of these patients may lead to AF impulses exclusively transmitted down the accessory pathway, and this can result in ventricular fibrillation. (If this happens, the patient will require immediate defibrillation.) Alternative therapies for the treatment of arrhythmia in this group include procainamide and amiodarone.
- Intravenous diltiazem or metoprolol are commonly used drugs for AF with RVR.
- Amiodarone has been used in patients with CHF who may otherwise not tolerate diltiazem or metoprolol. Digoxin may also be used, but its peak effect may not be for 6 hours.
Antiarrhythmic drugs
Antiarrhythmic drugs that can terminate atrial fibrillation include procainamide, disopyramide, propafenone, sotalol, flecainide, amiodarone, and ibutilide. The efficacy of antiarrhythmic drugs has been linked to the duration of atrial fibrillation.
The American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) Guidelines make the following recommendations regarding pharmacologic conversion of atrial fibrillation (AF):
- Conversion of AF less than or equal to 7 days14
- Agents with proven efficacy include dofetilide, flecainide, ibutilide, propafenone, and to a lesser degree, amiodarone and quinidine.
- Less effective or incompletely studied agents in this scenario include procainamide, digoxin, and sotalol.
- Conversion of AF lasting greater than 7 days
- Agents with proven efficacy include dofetilide, amiodarone, ibutilide, flecainide, propafenone, and quinidine.
- Less effective or incompletely studied agents in this scenario include procainamide, sotalol, and digoxin.
- Conversion of AF lasting greater 90 days - Oral propafenone, amiodarone, and dofetilide have been shown to be effective at converting chronic AF to normal sinus rhythm (NSR).
Anticoagulation
ACC/AHA/ESC 2006 Guidelines for Antithrombotic Therapy in Patients with AF5,9,15
Open table in new window
Table
| High risk factor | Moderate risk factor | Low risk |
| Prior CVA/TIA | Age >75 | Age 65-74 |
| Mechanical heart valve | HTN | Female gender |
| Mitral stenosis | CHF | CAD |
| EF <=35% | Thyrotoxicosis | |
| DM |
| High risk factor | Moderate risk factor | Low risk |
| Prior CVA/TIA | Age >75 | Age 65-74 |
| Mechanical heart valve | HTN | Female gender |
| Mitral stenosis | CHF | CAD |
| EF <=35% | Thyrotoxicosis | |
| DM |
Aspirin can be 81 mg or 325 mg
Warfarin - INR goal of 2-3
- Risk factors - Aspirin or no therapy
- One moderate risk factor - Aspirin or warfarin
- More than one moderate risk factor or one high risk factor - Warfarin
- Lone AF - Age 60-74 years, aspirin
- Age 60-74 years, CAD – Warfarin
Disposition
A number of studies have looked at whether low-risk patients with new-onset atrial fibrillation can be treated and discharged from an emergency department setting.16
- A study by Michael et al looked at 289 patients seen during an 18-month period in an emergency department setting.8 Sixty-two percent (180) underwent attempted chemical cardioversion with a 50% success rate, and 28% (80) had attempted electrical cardioversion with a 89% success rate. Ninety-three percent of electrical cardioversions were performed by emergency physicians. They concluded that cardioversion and immediate discharge of patients who present to the ED with acute atrial fibrillation appears to be both safe and effective.
- Reasons for hospitalization would include but not be limited to the following:
- Presence of comorbidities
- For workup or treatment of underlying etiology of atrial fibrillation, including evaluation for acute coronary syndrome or myocardial infarction
- For elderly patients
- For patients with underlying heart disease
- Patients at risk of complications from AF therapies
Consultations
- A cardiologist may become involved emergently if complicating factors are present or if the patient is experiencing ongoing cardiac ischemia or infarction not treatable with DC cardioversion, rate reduction measures, and standard chest pain protocols.17 A patient with acute myocardial infarction (AMI) and new-onset AF who is stable may benefit from simple rate-control measures (eg, intravenous beta-blockers) while being prepared for the catheterization laboratory and intravenous nitrates, heparin, and aspirin are begun. In the patient with an ST elevation MI, the main emphasis, however, is to minimize door to open artery time.
- A patient's cardiologist plays a vital role in determining the most appropriate long-term strategy for a patient with atrial fibrillation and provides crucial follow-up care.
Medication
Pharmacologic agents in atrial fibrillation (AF) fall into 1 of 2 classes: rate-controlling drugs and rhythm restoring/rhythm maintenance drugs (though some overlap exists with some drugs, such as amiodarone, exhibiting both qualities).
Rate-controlling drugs
In patients without ventricular preexcitation, rate is controlled most effectively with intravenous verapamil, diltiazem, or beta-adrenergic blockers. Beta-blockers are especially effective in the presence of thyrotoxicosis and increased sympathetic tone or in patients with myocardial ischemia/AMI. The non-hydropyridine calcium channel blockers may be chosen in patients lacking any history of heart failure and in patients with reactive airway disease.
Anecdotally, intravenous diltiazem has become many emergency medicine physician's first-line rate-controlling drug in patients without a history of heart failure.
Digoxin is ineffective in controlling ventricular rate during acute episodes.
In patients with acute or chronic heart failure, digoxin or amiodarone should be used. (Amiodarone does not currently have FDA approval for this intervention.)
Antiarrhythmic drugs
Antiarrhythmic drugs that can terminate atrial fibrillation include procainamide, disopyramide, propafenone, sotalol, flecainide, amiodarone, and ibutilide.
The efficacy of antiarrhythmic drugs has been linked to the duration of atrial fibrillation.
The American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) Guidelines make the following recommendations regarding pharmacologic conversion of AF:
- Conversion of AF less than or equal to 7 days
- Agents with proven efficacy include dofetilide, flecainide, ibutilide, propafenone, and to a lesser degree, amiodarone and quinidine.
- Less effective or incompletely studied agents in this scenario include procainamide, digoxin, and sotalol.
- Conversion of AF lasting greater than 7 days
- Agents with proven efficacy include dofetilide, amiodarone, ibutilide, flecainide, propafenone, and quinidine.
- Less effective or incompletely studied agents in this scenario include procainamide, sotalol, and digoxin.
- Conversion of AF lasting greater 90 days - Oral propafenone, amiodarone, and dofetilide have been shown to be effective at converting chronic AF to normal sinus rhythm (NSR).
Another newer drug is dronedarone, a deiodinated derivative of amiodarone that has no organ toxicity. Its use extends to atrial and ventricular arrhythmias. Dronedarone was approved by the US Food and Drug Administration July 2, 2009. It elicits multiple actions (all 4 Von Williams class effects). Unlike amiodarone, it does not have the iodine moiety. The lack of iodination may offer a better adverse-effect profile. Dronedarone has been shown to (1) have antiadrenergic effects, (2) prolong atrial and ventricular refractory periods, and (3) prolong atrioventricular node conduction and the paced QRS complex.
In animal models, dronedarone has been shown to decrease ischemia-induced ventricular arrhythmias. The clinical effects of dronedarone are now being examined in patients with atrial fibrillation and in patients with internal cardioverter-defibrillators (ICDs).
When considering drug therapy for atrial fibrillation, remember the treatment caveat: "Electrical cardioversion is the preferred modality in the patient whose condition is unstable."
Calcium channel blockers
These agents are more effective than digoxin when given orally for long-term rate control and should be the initial DOC. They reduce rate of AV nodal conduction and control ventricular response. Formulations administered IV are discussed as they apply to the control of severe symptoms related to a rapid ventricular rate in an emergent situation.
Diltiazem (Cardizem)
DOC for rate control in many cases. During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.
Adult
Initial dose: 0.25 mg/kg IV over 2 min as a bolus; may repeat at 0.35 mg/kg if inadequate rate reduction after 15 min; in patients weighing 80 kg, these 2 doses are 20 and 25 mg, respectively
Maintenance dose: 5-10 mg/h (up to 15 mg/h) IV for up to 24 h
Pediatric
Not established
May increase carbamazepine, digoxin, cyclosporine, theophylline levels; when administered with amiodarone, may cause bradycardia and decrease in cardiac output; when given with beta-blockers may increase cardiac depression; cimetidine may increase levels
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur
Verapamil (Calan, Isoptin, Verelan)
Can diminish PVCs associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia.
During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.
Adult
Initial dose: 2.5-5 mg IV bolus; may repeat, total dose not to exceed 15 mg; reduces ventricular rate within 5 min and can be followed by maintenance infusion
Maintenance dose: 0.05-0.2 mg/min IV infusion
Pediatric
<1 year: 0.1-0.2 mg/kg IV bolus over >2 min under continuous ECG monitoring; usual single-dose range 0.75-2 mg
1-15 years: 0.1-0.3 mg/kg IV bolus over >2 min; usual single-dose range 2-5 mg; not to exceed 5 mg
>15 years: Administer as in adults
May increase carbamazepine, digoxin, theophylline, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase levels
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hepatocellular injury may occur; transient elevations of transaminase levels with and without concomitant elevations in alkaline phosphatase and bilirubin levels have occurred (elevations have been transient and may disappear with continued verapamil treatment); monitor liver functions periodically
Beta-blockers
These agents slow the sinus rate and decrease AV nodal conduction. Beta-blockers now have more of a secondary role in AF rate control. Carefully monitor blood pressure.
Metoprolol (Lopressor)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.
During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult
5-15 mg IV over 5-15 min (5-mg increments)
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm (monitor patient closely and withdraw drug slowly); during IV administration, carefully monitor blood pressure, heart rate, and ECG
Esmolol (Brevibloc)
Ideal for use in patients at risk of complications from beta-blockade, especially those with mild-to-moderate LV dysfunction and peripheral vascular disease. Has a short half-life of 8 min, thus easily titratable to desired effect. In addition, therapy may be stopped quickly if needed.
Adult
Loading dose: 500 mcg/kg/min (0.5 mg/kg/min) IV infusion over 1 min; followed by a 4-min maintenance infusion of 50 mcg/kg/min (0.05 mg/kg/min); if adequate therapeutic effect observed over 5 min of drug administration, maintain maintenance infusion dosage with periodic adjustments prn; if adequate therapeutic effect not observed, repeat same loading dose over 1 min followed by increased maintenance infusion rate of 100 mcg/kg/min (0.1 mg/kg/min)
A quick calculation method is to take patient's body weight in kg and divide by 2 (eg, 70 kg/2 = 35 mg); this is the loading dose; multiply this dose by 0.1 (0.1 X 35 = 3.5 mg) to obtain the mg/kg/min drip rate
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, or contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, or catecholamine-depleting agents
Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen when medication withdrawn abruptly (withdraw drug slowly and monitor patient closely)
Class IA antiarrhythmics
These agents are used only for chemical conversion. They alter the electrophysiologic mechanisms responsible for arrhythmia.
Procainamide (Pronestyl)
Class IA antiarrhythmic used for PVCs. Increases refractory period of atria and ventricles. Myocardiac excitability reduced by increase in threshold for excitation and inhibition of ectopic pacemaker activity. IV form is treatment of choice if conduction is over an accessory pathway. May establish pharmacologic conversion to sinus rhythm.
Adult
Up to 17 mg/kg IV drip at rate of 20-30 mg/min under continuous cardiac monitoring; stop infusion if QRS widening or hypotension occurs
Pediatric
Not established
Can expect increased levels of procainamide metabolite NAPA in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine; may increase effect of skeletal muscle relaxants, quinidine, lidocaine, and neuromuscular blockers; ofloxacin inhibits tubular secretion of procainamide and may increase bioavailability; when taken concurrently with sparfloxacin, may increase risk of cardiotoxicity
Documented hypersensitivity; complete heart block or second- or third-degree heart block, if a pacemaker is not in place; torsade de pointes; systemic lupus erythematosus
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Fatal blood dyscrasias reported with therapeutic doses; close monitoring recommended during first 3 mo of therapy
May result in lupus erythematosus–like syndrome in about 20-30% of patients; plasma concentration of procainamide and active metabolite, NAPA, may be increased in renal failure; high or toxic concentrations may induce AV block or abnormal automaticity; caution in complete AV block, digitalis intoxication, organic heart disease, renal disease, and hepatic insufficiency
Quinidine (Cardioquin, Quinora)
Primarily an oral formulation that recently has been studied in sequential combination with verapamil versus digoxin for patients with stable, rate-controlled, acute-onset paroxysmal AF. After controlling rate with IV verapamil, 200 mg of oral quinidine was given q2h until conversion to NSR occurred, 1 g of quinidine was administered, or an adverse effect occurred. Approximately 84% of verapamil-quinidine group converted to NSR within 6 h, whereas 45% of digoxin-quinidine group converted to NSR within 6 h. This suggests that digoxin is relatively inferior in this group of patients. Moreover, Shreck et al found no advantage to adding digoxin to diltiazem for rate control. Quinidine prolongs effective refractory period and increases conduction time. Also has indirect anticholinergic effects and decreases vagal tone, which facilitates conduction in AV nodal junction.
Adult
200 mg PO q2-3h for 5-8 doses; followed by subsequent daily increases until sinus rhythm restored or side effects occur; not to exceed total daily dose of 3-4 g in any regimen; prior to administration, control ventricular rate and CHF (if present) with digoxin
Pediatric
30 mg/kg/d PO in 5 divided doses
Phenytoin, rifampin, and phenobarbital may decrease concentrations; toxicity increased when taken with ritonavir, sparfloxacin, beta-blockers, amiodarone, verapamil, cimetidine, alkalinizing agents, or nondepolarizing or depolarizing muscle relaxants; may enhance effect of anticoagulants
Documented hypersensitivity; complete AV block or intraventricular conduction defects; concurrent ritonavir or sparfloxacin
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in G-6-PD deficiency and patients with a tendency to develop granulocytopenia; avoid use in myocardial depression, hepatic or renal insufficiency, and myasthenia gravis
Class IC antiarrhythmics
These agents are used only in patients with structurally normal hearts (ie, absence of coronary artery disease or cardiomyopathy).
Propafenone (Rythmol)
Shortens upstroke velocity (Phase 0) of monophasic action potential. Reduces fast inward current carried by sodium ions in Purkinje fibers and, to a lesser extent, myocardial fibers. May increase diastolic excitability threshold and prolong effective refractory period prolonged. Reduces spontaneous automaticity and depresses triggered activity.
Indicated for the treatment of documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Appears to be effective in the treatment of supraventricular tachycardias including AF and atrial flutter. Not recommended in less severe ventricular arrhythmias, even if symptomatic. Use in conjunction with AV nodal blocking agents when given to patients in AF because conversion to AFL with 1:1 conduction (producing fast ventricular rates) has been noted.
Adult
150 mg PO q8h; increase up to a total dose of 900 mg/d prn
Pediatric
Not established
Rifampin may decrease plasma levels; quinidine may increase pharmacologic effects; propafenone may increase plasma levels of beta-blockers, cyclosporine, warfarin, and digoxin; CYP2D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity of propafenone
Documented hypersensitivity; preexisting second- or third-degree AV block, right bundle-branch block associated with left hemi-block (bifascicular block or trifascicular block), unless a pacemaker is present to sustain the cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in preexisting sinus node dysfunction, history of congestive heart failure, sick-sinus syndrome, post-MI, or myocardial dysfunction; reserve use only for life-threatening arrhythmias because of deaths associated with proarrhythmic effects of Class IC antiarrhythmics; adjust dose in renal or hepatic impairment
Flecainide (Tambocor)
Blocks sodium channels, producing dose-related decrease in intracardiac conduction in all parts of the heart. Increases electrical stimulation of threshold of ventricle, HIS-Purkinje system. Shortens Phase 2 and 3 repolarization, resulting in a decreased action potential duration and effective refractory period.
Indicated for the treatment of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms and paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. Indicated also for prevention of documented life-threatening ventricular arrhythmias, such as, sustained ventricular tachycardia. Not recommended in less severe ventricular arrhythmias even if patients are symptomatic. Use in conjunction with AV nodal blocking agents when given to patients in AF because conversion to AFL with 1:1 conduction (producing fast ventricular rates) can occur.
Adult
50 mg PO q12h; increase by 50 mg bid q4d until efficacy achieved
Pediatric
Not established
May increase toxicity of digoxin; beta-adrenergic blockers, verapamil, and disopyramide may have additive inotropic effects when administered with flecainide; CYP2D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity of flecainide; amiodarone may increase plasma levels of flecainide
Documented hypersensitivity; preexisting second- or third-degree AV block, right bundle-branch block associated with left hemi-block (bifascicular block or trifascicular block), unless a pacemaker is present to sustain the cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in preexisting sinus node dysfunction, history of congestive heart failure, sick-sinus syndrome, post-MI, or myocardial dysfunction; reserve use only for life-threatening arrhythmias because of deaths associated with proarrhythmic effects of Class IC antiarrhythmics; adjust dose in renal or hepatic impairment
Class III antiarrhythmics
These drugs may effectively establish a chemical conversion to sinus rhythm.
Sotalol (Betapace)
Class III antiarrhythmic agent that blocks K+ channels, prolongs action potential duration (APD), and lengthens QT interval. Noncardiac selective beta-adrenergic blocker. The D-isomer has less than 1/50 beta-blocking activity of the L-isomer. Sotalol possesses 30% of beta-blocking activity of propranolol.
Adult
80 mg PO bid initial dose; may gradually titrate up to 240-360 mg/d; allow 2-3 d between dosing increments; not to exceed 640 mg/d
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Documented hypersensitivity; sinus bradycardia; second- and third-degree AV block
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may decrease signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm (withdraw drug slowly and monitor patient closely); caution in hypokalemia, peripheral vascular disease, hypomagnesemia, CHF
Amiodarone (Cordarone)
May inhibit AV conduction and sinus node function, prolongs action potential and refractory period in myocardium, and inhibits adrenergic stimulation. Prior to administration, control ventricular rate and CHF (if present) with digoxin or calcium channel blockers. Blocks sodium channels and has high affinity for inactive channels. In addition, blocks potassium channels and weakly blocks calcium channels. Also blocks alpha- and beta-adrenergic receptors noncompetitively.
Adult
5 mg/kg IV over 30 min; followed by 1200 mg over 24 h
Pediatric
Loading dose: 6.3 mg/kg IV
Increases effect and blood levels of theophylline, quinidine, procainamide, phenytoin, methotrexate, flecainide, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity increased by ritonavir, sparfloxacin, and disopyramide; coadministration with calcium channel blockers may cause additive effect and decrease myocardial contractility further; cimetidine may increase levels
Documented hypersensitivity; complete AV block; intraventricular conduction defects; concurrent ritonavir or sparfloxacin
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects include pulmonary toxicity and fibrosis which can be life-threatening
Caution in thyroid or liver disease
Ibutilide (Corvert)
Class III antiarrhythmic agent, which may work by increasing action potential duration, thereby changing atrial cycle length variability; however, this mechanism remains controversial. Mean time to conversion 30 min. Two thirds of patients who converted were in sinus rhythm at 24 h. Ventricular arrhythmias occurred in 9.6% of patients and were mostly PVCs. The incidence of torsade de pointes was <2%.
Adult
Body weight <60 kg: 0.1 mL/kg (0.01 mg/kg) IV over 10 min
Body weight >60 kg: 1 mg (1 vial) IV over 10 min
If arrhythmia does not terminate within 10 min of end of initial infusion, may give second 10-min infusion of equal strength
Pediatric
Not established
Increases toxicity of quinidine and procainamide; concurrent administration with tricyclic antidepressants, phenothiazines, or astemizole (recalled from US market) may prolong QT interval; increases toxicity of concurrent digoxin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment
Dofetilide (Tikosyn)
Prototype of a "pure" class III agent. Blocks delayed rectifier current (IKr) and prolongs action potential duration; indeed, even at higher magnitudes, has no effect upon other depolarizing potassium currents (IKs and IKl). Terminates induced reentrant tachyarrhythmias (AF/flutter and ventricular tachycardia) and prevents their re-induction. At clinically prescribed concentrations, has no effect on sodium channels, which are associated with class I effects. Furthermore, no effect noted on alpha-receptors or adrenergic beta-receptors. Indicated for maintenance of NSR in patients with AF/atrial flutter of >1 wk duration who have been converted to NSR. Also indicated for conversion of AF and atrial flutter to NSR. Has not been effective for patients with paroxysmal AF. Torsade de pointes is only arrhythmia showing dose-response relationship. Incidence with supraventricular arrhythmia is 0.8%. Most torsade de pointes episodes occur within first 3 d of therapy.
If patients do not convert to NSR within 24 h of initiation of therapy, electrical cardioversion should be considered.
Has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance. Does not affect blood pressure.
Must be initiated with continuous ECG monitoring, which should continue for at least 12 h after conversion. Dose must be individualized according to CrCl and QTc (use QT interval if heart rate <60/min). No information on use of this drug for heart rates <50/min. Patients with AF should be anticoagulated according to established practice. Anticoagulation should be continued after cardioversion as per usual practice.
Adult
Step 1. Determine QTc using average of 5-10 beats; if QTc >440 ms (500 ms in those with ventricular conduction abnormalities), dofetilide is contraindicated
Step 2. Calculate CrCl prior to administration, using formulas:
CrCl (male) = (140-age) X body weight (kg) over 72 X serum creatinine (mg/dL)
CrCl (female) = (140-age) X body weight (kg) X 0.85 over 72 X serum creatinine (mg/dL)
Step 3. Determine starting dose as follows:
CrCl >60 mL/min: 500 mcg PO bid
CrCl 40-60 mL/min: 250 mcg PO bid
CrCl 20-40 mL/min: 125 mcg PO bid
CrCl <20 mL/min: Contraindicated
Step 4. Administer dofetilide and begin continuous ECG monitoring
Step 5. 2-3 h after administration of first dose, determine QTc; if QTc has increased by >15% compared to baseline or if the QTc is >500 ms (550 ms in those with ventricular conduction abnormalities), adjust subsequent doses as follows:
Starting dose 500 mcg PO bid, adjust to 250 mcg bid
Starting dose 250 mcg PO bid, adjust to 125 mcg bid
Starting dose 125 mcg PO bid, adjust to 125 mcg qd
Step 6. Continuously monitor for minimum of 3 d or for minimum of 12 h after conversion to NSR, whichever is greater
Pediatric
<18 years: Not established
See Contraindications above; drugs known to increase plasma levels of dofetilide include verapamil, cimetidine, trimethoprim, and ketoconazole; known inhibitors of renal cation transport include prochlorperazine, megestrol; drugs that prolong QT interval include, but are not limited to, phenothiazines, cisapride, bepridil, tricyclic antidepressants, and certain oral macrolide antibiotics
Hold class I or class III antiarrhythmic agents for at least 3 half-lives prior to dosing (terminal half-life is 10 h)
Does not affect pharmacokinetics of digoxin, but concomitant use of these two drugs has been associated with higher incidence of torsade de pointes; warfarin pharmacodynamics not altered by this medication
Congenital or acquired long QT syndromes, baseline QT interval or QTc > 440 ms (500 ms in patients with ventricular conduction abnormalities), severe renal impairment (CrCl < 20 mL/min), concomitant use of verapamil, cimetidine, trimethoprim, ketoconazole, or other drugs known to increase plasma levels of dofetilide, inhibit renal cation transport, or prolong QT interval
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment (CrCl guides dosing); caution in hepatic impairment (has not been studied in patients with severe hepatic impairment); caution in cardiac conduction problems—no effect on AV node conduction in patients with first-degree heart block (second- and third-degree not studied); has been used safely in conjunction with pacemakers
Antiarrhythmic Agent, Miscellaneous
Dronedarone is an antiarrhythmic agent with properties belonging to all 4 Vaughn-Williams antiarrhythmic classes.
Dronedarone (Multaq)
Blocks sodium channels, blocks beta1-adrenergic site, and alters adenyl cyclase generation (ie, negative inotropic effects); blocks potassium channels (eg, hERG) and therefore prolongs cardiac repolarization.
In a multinational clinical trial (n >4600), dronedarone reduced cardiovascular hospitalization or death from any cause by 24% compared with placebo.
Indicated to reduce risk for cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors (ie, age >70 y, hypertension, diabetes, history of CVA, LAD >50 mm or LVEF <40%) who are in sinus rhythm or who will be cardioverted.
Adult
400 mg PO bid with meals
Pediatric
Not established
CYP3A4 substrate, moderate CYP3A4 and CYP2D6 inhibitor; P-gP inhibitor
Avoid coadministration with CYP3A4 inhibitors (eg, itraconazole, azithromycin, erythromycin, grapefruit juice) that may decrease clearance and thereby increase dronedarone plasma levels (see Contraindications); avoid use with CYP3A4 inducers (eg, rifampin, carbamazepine) because of increased clearance and consequent reduction in dronedarone serum levels; use with other drugs that prolong QT interval (eg, phenothiazine, TCAs, macrolide antibiotics, class I and III antiarrhythmic agents) may cause life-threatening arrhythmias (see Contraindications)
When coadministered with P-gP substrates (eg, digoxin), P-gP substrate bioavailability may increase (consider discontinuing P-gp substrate or decrease P-gP substrate dose by 50%)
Coadministration increases serum levels of HMG-CoA reductase inhibitors (eg, atorvastatin), thereby increasing risk for adverse effects (eg, myopathy); monitor serum levels of CYP3A substrates with narrow therapeutic indexes (eg, sirolimus, tacrolimus) if coadministered
Coadministration with beta-blockers or calcium channel blockers requires lowered dose of these agents and dose should only be increased after ECG verification of tolerability
Documented hypersensitivity; severe heart failure (ie, NYHA class IV) or NYHA class II-III with recent decompensation requiring hospitalization or referral to heart failure program; second- or third-degree heart block or sick sinus syndrome (unless functioning pacemaker in place); bradycardia <50 bpm; QTc interval >500 milliseconds (coadministration with other drugs that prolong QT interval may cause torsade de pointes–type ventricular tachycardia); severe hepatic impairment; strong CYP3A4 inhibitors
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Boxed warning: May cause critical adverse reactions, including death, in patients with recent severe heart failure
Common adverse reactions include diarrhea, nausea, vomiting, fatigue, and asthenia; discontinue if new or worsening heart failure develops; monitor QT interval; hypomagnesemia and hypokalemia may increase risk for serious arrhythmic event
Cardiac glycosides
These drugs slow AV nodal conduction primarily by increasing vagal tone. They are used primarily in the setting of AF with CHF.
Digitalis, digoxin (Lanoxin)
Use of digoxin for acute rate control of AF in ED controversial. May be considered in patients with CHF secondary to impaired systolic ventricular function. However, more effective medications now available.
According to literature, digoxin shown to actually increase duration of episodes of paroxysmal AF, a result consistent with its action in decreasing atrial refractory period. Therapeutic concentrations of digoxin also do not prevent a rapid ventricular rate from developing in persons with paroxysmal AF. Therefore, digoxin should be avoided in persons with sinus rhythm with a history of paroxysmal AF.
Adult
Previously undigitalized patients: 400-600 mcg (0.4-0.6 mg) IV single initial dose usually produces detectable effect in 5-30 min; effect becomes maximal in 1-4 h
Pediatric
<2 years: Not established
2-5 years: 25-35 mcg/kg IV
5-10 years: 15-20 mcg/kg IV
>10 years: 8-12 mcg/kg IV
Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypokalemia may reduce positive inotropic effect; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; use caution in hypothyroidism, hypoxia, and acute myocarditis
More on Atrial Fibrillation |
| Overview: Atrial Fibrillation |
| Differential Diagnoses & Workup: Atrial Fibrillation |
 Treatment & Medication: Atrial Fibrillation |
| Follow-up: Atrial Fibrillation |
| Multimedia: Atrial Fibrillation |
| References |
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Further Reading
Keywords
atrial fibrillation, AF, atrial fib, atrial fibrillation treatment, bradyarrhythmia, tachyarrhythmia, arrhythmia, heart disease, acute myocardial infarction, AMI, congestive heart disease, CHD, coronary artery disease, CAD, cardiovascular disease, heart attack, rhythm disturbance, atrioventricular node, AV node, palpitations, dyspnea, chest pain, angina, syncope, hypotension, congestive heart failure, CHF, jugular venous distension, hypertension, valvular heart disease, rheumatic heart disease
