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Atrial Fibrillation Last Updated: January 22, 2007 |
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| Synonyms and related keywords: AF, atrial flutter, arrhythmia, AFL, supraventricular tachycardia, SVT, congestive heart failure, CHF, ventriculartachycardia, VT, ventricular fibrillation, VF, coronary artery disease, CAD, thromboembolic stroke, uncontrolled hypertension, coronary disease, valvular heart disease, acute pulmonary processes, acute pulmonary disease,
hyperthyroidism, acute alcohol intoxication, holiday heart, Saturday night heart, illicit narcotic abuse, drug abuse, tachycardia-induced cardiomyopathy, rheumatic heart disease, rheumatic valvular disease, hypertension, diabetes, thromboembolism, recurrent AF, paroxysmal AF, permanent AF, chronic AF, thyrotoxicosis, electrolyte abnormalities, acute ethanol intoxication, atrial premature beats, Holter monitoring, hypertensive heart disease, dilated cardiomyopathy, atrial cardiomyopathy, Maze procedure, electrical cardioversion, ischemic stroke, Wolff-Parkinson-White syndrome, hepatojugular reflex
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: Lawrence Rosenthal, MD, PhD, Associate Professor of Medicine, Division of Cardiology, Director of Clinical Electrophysiology and Pacing, Department of Internal Medicine, Division of Cardiovascular Medicine, University of Massachusetts Memorial Medical Center |
| Lawrence Rosenthal, MD, PhD, is a member of the following medical societies:
American College of Cardiology,
American Heart Association, New England Electrophysiology Society, and
North American Society for Pacing and Electrophysiology |
| Editor(s): Alan D Forker, MD, Professor of Medicine, Program Director of Cardiovascular Fellowship, Department of Medicine, Mid America Heart Institute, University of Missouri at Kansas City School of Medicine; Co-Director, Lipid Diabetes Research Center, Saint Luke's Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Brian Olshansky, MD, Professor of Medicine, Director of Cardiac Electrophysiology, Department of Internal Medicine, University of Iowa Hospitals;
Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital;
and Leonard Ganz, MD, Associate Professor of Medicine, Temple University School of Medicine; Cardiac Electrophysiologist, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Cent, West Penn Hospital |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: Atrial fibrillation (AF) is a common arrhythmia (see Image 1) and is a significant public health problem in the United States, affecting 2.2 million Americans and almost 5% of the population older than 69 years and 8% of the population older than 80 years. Thus, the prevalence of AF increases with advancing age. Data from the Framingham heart study show that AF is associated with a 1.5- to 1.9-fold higher risk of death, which may be due to thromboembolic stroke. While patients can be asymptomatic, many experience a wide variety of symptoms, including palpitations, dyspnea, fatigue, dizziness, angina, and congestive heart failure (CHF). In addition, the arrhythmia can be associated with hemodynamic dysfunction, tachycardia-induced cardiomyopathy, and systemic embolism.
Overall, approximately 15-25% of all strokes in the United States (75,000/y) can be attributed to AF. Known risk factors include male sex, valvular heart disease (rheumatic valvular disease), CHF, hypertension, and diabetes. Additional risk factors, such as advanced age and prior history of stroke, diabetes, and hypertension, place patients with preexisting AF at even higher risk for further comorbidities such as stroke. Patients with nonvalvular AF and risk factors have a 5-fold increased risk for stroke. Patients with rheumatic heart disease and AF have an even higher risk for stroke (17-fold). At least 4 large clinical trials have clearly demonstrated that anticoagulation with warfarin decreases the risk of stroke by 50-80%.
Given the frequency of these comorbidities, management can result in significant medical costs. Therapeutic goals include rate control, maintenance of sinus rhythm, and prevention of thromboembolism. Additionally, current practice and economic pressures force many physicians to reconsider outpatient treatment options. Pathophysiology: Several classification schemas have been proposed for the study of AF, but none fully accounts for all aspects of AF. A number of different labels and nomenclature have been used to describe patterns of AF, including acute, chronic, paroxysmal, intermittent, and permanent. The vagaries of each of these definitions make comparing the results of studies assessing the magnitude and treatment of AF difficult.
Recently published guidelines from expert committees of the American College of Cardiology/American Heart Association and European Society of Cardiology on the treatment of patients with AF suggest that AF be classified into 3 patterns. These include a first detectable episode, irrespective of whether it is symptomatic or self-limited. Recurrent AF is considered to be present when a patient has 2 or more episodes of AF. If AF terminates spontaneously, then recurrent AF is designated as paroxysmal; if this arrhythmia becomes sustained, then AF is considered persistent (irrespective of whether AF is terminated with pharmacologic therapy or electrical cardioversion).
Persistent AF may be either the first presentation of AF or the result of recurrent episodes of paroxysmal AF. Patients with persistent AF also include patients with long-standing AF in whom cardioversion has not been indicated or attempted, often leading to permanent AF. Permanent AF is recognized as the accepted rhythm, and the only treatment goals are rate control and anticoagulation.
This classification schema pertains to cases that are not related to a reversible cause of AF (eg, thyrotoxicosis, electrolyte abnormalities, acute ethanol intoxication). The occurrence of AF secondary to acute myocardial infarction, cardiac surgery, pericarditis, pulmonary embolism, or acute pulmonary disease is considered separately because in these situations, AF is less likely to recur once the precipitating condition has been resolved and adequately treated.
Some patients with paroxysmal AF, typically younger patients, have been found to have distinct electrically active foci within their pulmonary veins. These patients generally have many atrial premature beats noted on Holter monitoring. Isolation or elimination of these foci can lead to elimination of the trigger for paroxysms of AF.
Patients can also have AF as a secondary arrhythmia associated with cardiac disease that affects the atria (eg, CHF, hypertensive heart disease, rheumatic heart disease, coronary artery disease [CAD]). These patients tend to be older, and AF is more likely to be chronic. Paroxysmal AF may progress to chronic AF, and aggressive attempts to restore and maintain sinus rhythm may prevent comorbidities associated with AF.
Persistent AF with an uncontrolled, rapid ventricular heart rate response can cause a dilated cardiomyopathy and can lead to electrical remodeling in the atria (atrial cardiomyopathy). Therapy, such as drugs or atrioventricular (AV) nodal ablation and permanent pacemaker implantation, to control the ventricular rate can improve left ventricular (LV) function and improve quality-of-life scores.
New developments aimed at curing AF are being actively explored. By reducing the critical mass required to sustain AF with either surgical or catheter-based compartmentalization of the atria (ie, MAZE procedure), fibrillatory wavelets collide with fixed anatomic obstacles, such as suture lines or complete lines of ablation, thus eliminating or reducing the chance of chronic AF. Some patients with focal origins of their AF also may be candidates for catheter ablation. Still, much remains to be accomplished before either of these procedures is appropriate for primary treatment. Frequency:
- In the US: AF affects 2.2 million Americans. It can occur in the absence of comorbidities, as it does in 10-15% of individuals (lone AF); however, AF is associated more frequently with hypertension; organic heart disease; CHF; ischemic heart disease; and valvular, dilated, hypertrophic, restrictive, and congenital cardiomyopathies. Paroxysmal AF is commonly associated with cardiac surgery, pulmonary disease, thyrotoxicosis, acute ethanol intoxication, and electrolyte imbalance. Given the almost epidemic proportions of patients with AF, clinicians must be aware of the multiple mechanisms and presentations and then correct the underlying etiology, if possible. For example, a logical decision may be to correct an overactive thyroid gland before attempting cardioversion.
Mortality/Morbidity: AF is associated with increased morbidity. The static nature of blood flow during AF can lead to the development of thrombus, most commonly in the left atrial appendage. Dislodgement of clot can lead to embolic phenomena, including stroke. Thus, anticoagulation remains the primary focus in appropriate patient populations. A target international normalized ratio of 2-3 limits the risks of hemorrhage while providing protection against the formation of thrombus.
Age:
- AF is strongly age-dependent, affecting 4% of individuals older than 60 years and 8% of persons older than 80 years. The rate of ischemic stroke among elderly patients not treated with warfarin averages approximately 5% per year.
History: Focus the initial evaluation on hemodynamic stability and potential causes. Consider immediate electrical cardioversion for patients with impending hemodynamic collapse or evidence of cardiac ischemia. - A thorough history, physical examination, and 12-lead ECG are key to making an accurate diagnosis.
- Examine the ECG tracings for evidence of Wolff-Parkinson-White syndrome, which may predispose a small percentage of patients to sudden cardiac death. In these patients, AF can lead to rapid ventricular rates and, subsequently, degenerate into ventricular fibrillation, especially when AV nodal blocking agents are used.
Physical: The physical examination determines whether patients need immediate restoration of sinus rhythm or whether they can be treated more conservatively. - Vital signs - Assessment of vital signs and oxygen saturation for evidence of pulmonary vascular congestion
- Head and neck - May reveal elevated venous pressures or cyanotic lips
- Pulmonary - May reveal rales and evidence of pleural effusion
- Cardiac - May reveal CHF with a displaced point of maximal impulse and an S3 and other potential important murmurs
- Abdomen - May reveal ascites and slight pressure in the area of the liver; may produce a hepatojugular reflex consistent with passive liver congestion and CHF
- Lower extremities - May reveal edema
Causes: The most common cause is advancing age; however, uncontrolled hypertension, coronary disease, CHF, valvular heart disease, acute pulmonary processes, hyperthyroidism, acute alcohol intoxication (ie, holiday heart, Saturday night heart), and illicit narcotic abuse should also be considered. Patients having undergone cardiac, pulmonary, or esophageal surgery have a 20-40% postoperative incidence of atrial fibrillation (AF). Patients with congenital heart disease are at higher risk for developing AF. - Increased atrial pressure - Mitral or tricuspid valvular disease, myocardial disease leading to systolic or diastolic dysfunction, systemic or pulmonary hypertension, intracardiac tumors or thrombi
- Atrial ischemia - Coronary artery disease
- Inflammatory disease - Pericarditis; amyloidosis; myocarditis; age-induced atrial fibrosis; postoperative cardiac, pulmonary, esophageal surgeries
- Drugs - Caffeine, alcohol
- Endocrine disorders - Hyperthyroidism, pheochromocytoma
- Neurologic - Subarachnoid hemorrhage, major stroke
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DIFFERENTIALS
| Section 4 of 11 |
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Atrial Flutter
Atrial Tachycardia
Atrioventricular Nodal Reentry Tachycardia (AVNRT)
Paroxysmal Supraventricular Tachycardia
Wolff-Parkinson-White Syndrome
Other Problems to be Considered:
Digoxin toxicity |
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Lab Studies:
- Perform at least one thyroid function study to exclude hyperthyroidism.
- Measure electrolytes and BUN/creatinine.
- Measure the digoxin level if toxicity is suspected.
- A toxicology screen or ethanol level may be appropriate in the right clinical scenario to rule out acute intoxication as the cause of AF.
Imaging Studies:
- In hemodynamically stable patients, obtaining a transthoracic echocardiogram is reasonable to evaluate for LV function and cardiac chamber size, valvular heart disease, pulmonary hypertension, LV hypertrophy, and pericardial effusion.
- In some instances, performing a transesophageal echocardiogram (TEE) is desirable to look for specific evidence of left atrial or LV thrombus prior to cardioversion. If thrombus is present, cardioversion should be delayed because the restoration of atrial mechanical contraction associated with conversion to sinus rhythm may cause embolization in the immediate postcardioversion period or as long as 2-3 weeks later. While left atrial smoke (or spontaneous contrast) is present in many patients, it does not imply thrombus. Synchronized cardioversion can be accomplished safely if left atrial and LV thrombi are not present. Despite a TEE finding that is negative for thrombus, patients still require anticoagulation with heparin and warfarin after cardioversion.
- If left atrial ablation procedures are planned, then 3-dimensional imaging technologies (CT scan or MRI) are desirable. Raw data can be processed to create anatomic maps of the left atrium and pulmonary veins.
Other Tests:
- ECG findings usually confirm the diagnosis of AF.
- The ventricular rate typically is irregular.
- Discrete P waves are absent; instead, undulating fibrillatory (f) waves are present (see Image 1).
Procedures:
- Synchronized direct current
- Cardioversion is synchronized to the R wave to prevent the potential for a nonsynchronized shock to be delivered during the vulnerable phase of the T wave and the initiation of ventricular fibrillation.
- Direct-current cardioversion is used to restore sinus rhythm if patients are anticoagulated adequately with a therapeutic international normalized ratio (INR) and remain in AF.
- In most patients, the procedure can be performed safely in an outpatient setting.
- Administer either intravenous sedation, according to sedation guidelines, or general anesthesia for patient comfort and safety.
- Defibrillating patches are positioned in various positions, including the right anterior and left posterior positions to allow electrical vectors to defibrillate the atria, and in more standard positions such as anterior and lateral positions.
- A high success rate should be expected, with the realization that some patients remain in sinus rhythm transiently, only to revert back to AF. If initially unsuccessful, consider using an intravenous infusion of ibutilide (1 mg), which reduces the defibrillation thresholds, or use different electrical vectors. Defibrillators with biphasic waveforms have been demonstrated to be more efficacious in converting AF to sinus rhythm.
- Synchronized electrical cardioversion for acute onset
- Consider immediate cardioversion for patients with AF of less than 48 hours' duration because the risk of embolic stroke is small. If the exact time cannot be determined accurately or is longer than 48 hours in duration, patients should receive either a TEE to assess for atrial thrombus prior to cardioversion or anticoagulation therapy for 4 weeks with an INR goal of 2-3 prior to elective cardioversion. If AF duration is questionable or is longer than 48 hours and the TEE shows no evidence of atrial thrombus, anticoagulation is still indicated postprocedure, and the initiation of intravenous heparin is warranted while warfarin therapy is initiated and while the INR rises to therapeutic levels. Low–molecular-weight heparin (1 mg/kg bid) may be used in outpatient settings in conjunction with warfarin therapy.
- Alternatively, use the traditional right anterior and left lateral position of patches or external paddles. Once the patient is adequately sedated, a synchronized shock of 200-360 J is usually required for conversion to sinus rhythm. Body habitus and urgency are guides to choosing the shock energy. For example, a person who is obese with a large anteroposterior diameter probably will require 360 J, and an elderly person with thin body habitus might require only 200 J. Required energies are lower with biphasic waveforms (100-200 J).
- Two sets of patches can be used to successfully cardiovert patients in whom a single maximal shock with 1 set of patches fails. Two external defibrillators and 2 sets of defibrillation patches are required. Vectors are crossed so that 1 set of patches is placed anteriorly left of the sternum and posteriorly right of the spine. The second set of patches is placed anteriorly right of the sternum and posteriorly left of the spine. The 2 defibrillators may be activated simultaneously, in synchronized fashion, or with a slight delay after the first discharge. This method may succeed when a single set of patches fails.
- Internal cardioversion is also possible and requires an electrophysiologist and an electrophysiologic laboratory. Typically, intracardiac catheters are positioned in the right atrium and in the coronary sinus. Synchronized shocks are delivered between the 2 catheters, with energies from 1-100 J. Alternatively, defibrillating current may be passed between a single intracardiac catheter (right atrium, coronary sinus) and a single cutaneous patch placed anteriorly or posteriorly.
- External cardiac defibrillators with biphasic shocking waveforms have received approval from the US Food and Drug Administration (FDA). In 2003, Neal et al reported that these devices have been shown to dramatically reduce energy requirements and improve efficacy compared with standard monophasic devices.
- Chemical conversion to sinus rhythm
- Hemodynamically stable patients with AF can be converted to sinus rhythm with large doses of oral agents or with intravenous agents. Large single doses of flecainide (300 mg) or propafenone (450-600 mg) given orally have been shown to convert patients to sinus rhythm. The drug is given in a monitored setting, preferably in an inpatient setting. Patients should not have a QTc longer than 460 milliseconds and should not be taking concomitant antiarrhythmic agents.
- Alternatively, patients can be given intravenous doses of procainamide (<18 mg/kg/h) or ibutilide (1 mg over 15 min, may be repeated after 30 min). Some clinicians also preload patients with intravenous magnesium (2 g) prior to infusing ibutilide as a preventative measure for torsade de pointes (TdP). Both agents should be administered in a highly monitored setting (ICU), with an external defibrillator at the bedside, and with special care to ensure electrolyte values are within normal limits. Monitor blood pressure and heart rate, and monitor for signs of QRS widening (ie, with frequent ECGs).
- Patients with CHF and cardiogenic shock are not candidates for this type of procedure. Involving a cardiologist or electrophysiologist would be reasonable if intravenous conversion is being considered because TdP has been documented.
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TREATMENT
| Section 6 of 11 |
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Medical Care: The initial goal in the management of AF is rate control and anticoagulation, with an eventual goal of restoration and maintenance of sinus rhythm. However, few prospective, randomized controlled trial data are available to indicate to the clinician whether patients with symptomatic or asymptomatic AF do better simply with rate control and anticoagulation or with aggressive attempts to maintain sinus rhythm with repeated electrical cardioversion and antiarrhythmic agents.
Restoration of sinus rhythm with regularization of the heart's rhythm improves cardiac hemodynamics and quality of life and reduces the risk of thromboembolic complications. Additional benefits include maintaining the appropriate physiologic responses to exercise and the atrial contribution to the cardiac output, thus preventing atrial dilation and possible LV dysfunction. Thus, most clinicians initially focus on rhythm control, and rate control is pursued only when rhythm control fails.
Two randomized controlled trials have demonstrated that a strategy aimed at restoring (and maintaining) sinus rhythm neither improves the survival rate nor reduces the risk of stroke. In the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, 4060 subjects aged 65 years or older whose atrial fibrillation was likely to be recurrent and who were at risk for stroke were randomized to a strategy of rhythm control (cardioversion to sinus rhythm plus drugs to maintain sinus rhythm) versus a strategy of rate control (in which no attempt was made to restore or maintain normal sinus rhythm). An insignificant trend toward increased mortality was noted in the rate-control group, and, importantly, no evidence suggested that the rhythm-control strategy protected patients from stroke.
The AFFIRM study (and similar findings from the smaller Rate Control Versus Electrical Cardioversion [RACE] trial) has led to the development of consensus guidelines advocating a rate-control strategy for most atrial fibrillation patients. Thus, rhythm control may be a desirable pursuit in patients who become symptomatic during episodes of AF. The importance of anticoagulation with warfarin with a target INR 2-3 was underscored.
With the goal of maintaining sinus rhythm and preventing AF, new therapies are being actively explored, including single- and dual-site atrial-based pacing to prevent AF and atrial defibrillators to restore sinus rhythm soon after a spontaneous episode. Surgical and catheter-based therapies to compartmentalize the atria and localize focal triggers (in the pulmonary veins) are being evaluated and refined. - Rate control
- Beta-blockers and calcium channel blockers are the drugs of choice for rate control. These drugs can be administered intravenously and orally. They are effective at rest and with exertion. Caution should be exercised in patients with reactive airway disease given beta-blockers.
- Digoxin can be used in the acute setting but does little to control the ventricular rate in active patients. In addition, it has no antiarrhythmic effects and actually may promote AF by shortening atrial refractory periods. Digoxin is indicated in patients with heart failure and reduced LV function.
- Anticoagulation
- AF is recognized as a powerful risk factor for stroke. One of the most important concerns in treating patients is the need for anticoagulation. Effective anticoagulation in patients with AF reduces the risk of stroke 3-fold. Patients with newly diagnosed AF and patients awaiting electrical cardioversion can be started on intravenous heparin (activated partial thromboplastin time [aPTT] of 45-60 seconds) or low–molecular-weight heparin (1 mg/kg bid).
- Patients can be concomitantly started on warfarin in an inpatient setting while awaiting a therapeutic INR value (2-3). Many practices have developed specialized anticoagulation clinics to closely monitor INR values.
- Long-term prophylaxis
- Patients have a risk of stroke or peripheral embolism that is approximately 5 times that of people in sinus rhythm. This risk can be reduced greatly with warfarin.
- Patients with no structural heart disease and patients younger than 65 years have an extremely low risk for stroke. Generally, they do not need anticoagulation. Aspirin at 325 mg/d is recommended.
- The combination of age and identifiable risk factors compounds the risk of embolization and stroke. Established risk factors include prior stroke or transient ischemic attack, diabetes, hypertension, CAD, mitral stenosis, prosthetic valve, CHF, echocardiographic findings of an enlarged left atrium, and global LV dysfunction. The following is a summary of the current recommendations regarding anticoagulation in the treatment of AF:
- Patients younger than 65 years with risk factors receive warfarin therapy with a goal INR of 2-3.
- Patients younger than 65 years with no risk factors receive ASA therapy or no treatment.
- Patients older than 65 years receive warfarin therapy with a goal INR of 2-3.
- Patients older than 75 years with no risk factors receive ASA therapy.
- Acute conversion to sinus rhythm
- The decision to restore sinus rhythm acutely depends on the hemodynamic status of the patient.
- Consideration of impending hemodynamic collapse or acute cardiac ischemia may influence the decision to cardiovert immediately.
- Elective conversion to sinus rhythm
- Exactly how long AF must be present before the risk of atrial thrombus and subsequent thromboembolism develops is uncertain. Certainly, the longer patients are in AF, the more likely they are to develop atrial thrombus. In general, if the arrhythmia is present for less than 48 hours, cardioversion can be accomplished safely without further need for anticoagulation. If uncertain, a TEE could be performed to exclude left atrial thrombus. In any case, acute conversion must be accompanied by anticoagulation.
- In patients with AF longer than 48 hours in duration or of unknown duration, cardioversion is not recommended until sufficient anticoagulation is achieved. The most conservative route is to anticoagulate with warfarin (INR of 2-3) for 3-4 weeks prior to any attempt to restore sinus rhythm.
- Because embolic events can occur following cardioversion as atrial mechanical function returns, continue anticoagulation for an additional 4-6 weeks. Alternatively, initially perform a TEE, and if no thrombus is present, cardiovert and therapeutically anticoagulate for a minimum of 4-6 weeks after sinus rhythm is restored.
- Pacing to prevent AF
- The fact that ventricular-based pacing (VVI mode) does not prevent AF in patients with sick sinus syndrome is well documented. Retrospective data suggest that atrial-based pacing (AAI, DDD modes) reduces the risk of developing AF and increases the interval between episodes in patients with sick sinus syndrome.
- Implantable atrial defibrillators
- Early conversion to sinus rhythm is desirable because patients do not require long-term anticoagulation. AF-free intervals have been shown to be prolonged with early AF termination.
- Defibrillation energy requirements are typically higher than the patient's pain threshold. This can represent a problem for most patients. Painless therapy (eg, atrial burst pacing to extinguish AF) is successful approximately 20% of the time, making this form of therapy desirable in patients with poorly tolerated AF.
Surgical Care: Since its inception, surgical compartmentalization of the atria, or the MAZE procedure, has evolved as an exciting procedure with a potential to cure AF. Quite simply, the atria are transected and resutured to reduce the critical mass required for the maintenance of AF. Early experience shows that atrial transport is restored postoperatively and that long-term anticoagulation is not required. The downside remains the need for an open chest procedure; however, thoracoscopic procedures may reduce hospitalization and recovery times in the future. The surgical MAZE procedure remains an attractive procedure for patients with AF who are undergoing concomitant mitral valve procedures. Its role as a primary therapy for AF is doubtful. Catheter ablation has taken the following 3 paths in the attempt to cure or manage AF. - Compartmentalization of the atria with continuous ablation lines of block
- Parallel to the surgical MAZE procedure, electrophysiologists are attempting to recreate surgical suture lines with radiofrequency lesions (still investigational).
- The procedures tend to be many hours in duration, and the success rates are somewhat disappointing, with left atrial reentrant tachycardias appearing (requiring further ablation procedures).
- Researchers are unsure which areas of the atria are necessary to sustain AF. Purely right-sided lesions are not sufficient to eliminate AF, making left atrial procedures necessary. In addition, gaps in linear lesions can be difficult to find.
- Research currently focuses on catheter designs to deliver linear continuous lesions in both atria.
- Catheter ablation of focal triggers of AF
- In some patients, AF seems to be triggered by electrically active pulmonary vein foci. These foci can trigger the atria to fibrillate.
- Patients typically have an abundance of ectopic atrial beats noted on 24-hour Holter monitoring. Electrical isolation of individual pulmonary veins, and thus the ectopic foci, is performed successfully at many centers, and patient selection is key to success. A combined procedure including individual pulmonary vein isolation, as well as left atrial ablation (ie, encircling pulmonary vein pairs, connecting right and left pairs along the left atrial roof, and connection to the mitral valve annulus) is often necessary. The use of chest CT or MRI can be used to recreate 3-dimensional anatomy in the left atrium, thus aiding in mapping and creating contiguous lines in the left atrium. In addition, multiple procedures are often necessary.
- Complications are generally in the 5% range and include pulmonary vein stenosis (that can be symptomatic), perforation, thromboembolism, and tamponade. Still, cure rates as high as 70-80% have been reported in properly selected patients (patients with frequent atrial premature beats and episodes of paroxysmal AF).
- Atrioventricular node ablation and insertion of a permanent pacemaker
- AV node ablation may represent an alternative in patients with chronic AF and an uncontrolled ventricular response despite aggressive medical therapy.
- Catheter ablation of the AV junction permanently interrupts conduction from the atria to the ventricles.
- Because the result is permanent AV block, a permanent pacemaker is required. AF may still exist, but the pacemaker governs the ventricular response.
- The risk of thromboembolism is unchanged, and patients still require anticoagulation; however, most patients are relieved of their symptoms.
- During the first 1-3 months, the pacing rate must be programmed in the 80- to 90-beat range to prevent TdP, which has been reported in the literature, presumably due to slow ventricular rates and the occurrence of early after-depolarizations.
- Improvements in LV size and function, functional class, and quality-of-life scores have been demonstrated.
Consultations: - Consultation with a cardiac electrophysiologist or knowledgeable physician is recommended prior to antiarrhythmic drug initiation.
Diet: - Diet restrictions, if any, are as appropriate for the underlying heart disease and any other comorbidities (eg, diabetes mellitus).
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MEDICATION
| Section 7 of 11 |
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The goals of medical therapy are to maintain sinus rhythm, avoid the risk of complications (eg, stroke), and minimize patient symptoms. Warfarin represents the cornerstone of anticoagulant therapy for patients in chronic AF or those awaiting conversion to sinus rhythm. The goal of antiarrhythmic drug therapy is reducing the duration and frequency of episodes, thus improving the quality of life and eliminating the need for long-term anticoagulation, which decreases the potential risk of serious bleeding.
Antiarrhythmic agents are commonly used to prevent AF recurrence. Currently, the FDA has approved 5 antiarrhythmic drugs for the treatment of AF (ie, quinidine, flecainide, propafenone, sotalol, dofetilide); however, other antiarrhythmic agents (eg, amiodarone) are used in an off-label fashion with great clinical efficacy. Use antiarrhythmic agents with great caution because they can cause proarrhythmia, exacerbate a preexisting arrhythmia, or provoke a new arrhythmia. Proarrhythmia can be bradycardic or tachycardic, atrial or ventricular. In addition, adverse effects can cause severe comorbidities and even death. Consultation with a cardiac electrophysiologist or knowledgeable physician is recommended prior to antiarrhythmic drug initiation.
Finally, given current hospital constraints and pressure to initiate these agents in an outpatient setting, carefully reconsider specific patient populations at low and acceptable risks for outpatient drug initiation. Whether these agents can be started in an outpatient setting remains controversial. Initiation of drug therapy is generally recommended in a monitored inpatient setting, especially in patients with known structural heart disease or risk factors for toxicity. Proarrhythmia is the most common adverse effect during the loading phase. Proarrhythmic risk is unpredictable; therefore, inpatient loading can lead to a false sense of security regarding future arrhythmic events.
Drug Category: Atrioventricular nodal conduction blockers -- Used to slow ventricular response by slowing AV nodal conduction during AF or AFL. Also indicated for use in conjunction with class IA and IC antiarrhythmics, which slow AF/flutter rate and may cause more rapid ventricular response. Drug Name
| Propranolol (Inderal) -- Class II antiarrhythmic, nonselective, beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases automaticity of contractions. |
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| Adult Dose | 1-3 mg (under careful monitoring); not to exceed 1 mg/min to avoid lowering blood pressure and causing cardiac standstill
Allow time for drug to reach site of action (particularly if slow circulation); administer second dose after 2 min prn; thereafter, do not administer additional drug after desired alteration in rate or rhythm achieved; switch to 10-160 mg PO bid| Pediatric Dose | 2-4 mg/kg/d PO divided bid (1-2 mg/kg bid)
IV use not recommended; however, for arrhythmias, 0.01-0.1 mg/kg, not to exceed 1 mg/dose, by slow push has been recommended; change to PO as soon as possible| Contraindications | Documented hypersensitivity; uncompensated CHF; bradycardia, cardiogenic shock; AV conduction abnormalities |
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| Interactions | Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor patient closely |
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Drug Name
| Atenolol (Tenormin) or esmolol (Brevibloc) -- Selectively blocks beta-1 receptors with little or no effect on beta-2 types. Esmolol is excellent for use in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed. |
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| Adult Dose | Atenolol: Up to 200 mg PO qd
Esmolol: 250-500 mcg/kg/min IV for 1 min loading dose followed by 4-min maintenance infusion of 50 mcg/kg/min
If adequate therapeutic effect not observed within 5 min, repeat loading dose and follow with maintenance infusion using increments of 50 mcg/kg/min (for 4 min); sequence may be repeated up to 4 times prn
As desired heart rate is approached, omit loading infusion and reduce incremental dose of maintenance infusion from 50 mcg/kg/min to 25 mcg/kg/min or lower; interval between titration steps may be increased from 5 min to 10 min if needed| Pediatric Dose | Atenolol: Not established
Esmolol: Not established; 100-500 mcg/kg IV administered over 1 min suggested| Contraindications | Documented hypersensitivity, CHF, pulmonary edema, cardiogenic shock, AV conduction abnormalities, heart block (without a pacemaker) |
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| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased 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 |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV, carefully monitor BP, heart rate, and ECG |
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Drug Name
| Metoprolol (Lopressor) -- Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG. |
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| Adult Dose | 5 mg IV for 3 doses q2-5 min; then up to 200 mg PO bid |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity, uncompensated CHF, bradycardia, asthma, cardiogenic shock, and AV conduction abnormalities |
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| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased 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 |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| 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 |
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Drug Name
| Digoxin (Lanoxin) -- Slows sinus node and AV node via vagomimetic effect and not very effective if sympathetic tone is increased. Generally not recommended unless depressed LV function is present. |
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| Adult Dose | Loading dose: 1.5-2 mg PO/IV in divided dose over 1-2 d
Maintenance dose: 0.25 mg PO/IV qd| Pediatric Dose | Premature neonates: 15-25 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 4-6 mcg/kg/d PO/IV divided bid
Neonates: 20-30 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 5-8 mcg/kg/d PO/IV divided bid
<2 years: 30-50 mcg/kg PO/IV divided into 3 or more doses (first dose half total dose), then remaining doses q6-8h; maintenance of 7.5-12 mcg/kg/d PO/IV divided bid
2-5 years: 25-35 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 6-9 mcg/kg/d PO/IV divided bid
6-10 years: 15-30 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 4-8 mcg/kg/d PO/IV divided bid
>10 years: 8-12 mcg/kg PO/IV divided into 3 or more doses, (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 2-3 mcg/kg/d PO/IV qd| Contraindications | Documented hypersensitivity, beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, carotid sinus syndrome |
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| Interactions | Medications that may increase 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 levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, and procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity; hypocalcemia can make digoxin ineffective until serum calcium levels are normal; institute magnesium replacement therapy in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis |
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Drug Category: Antiarrhythmics, class IA -- Quinidine, procainamide, and disopyramide are IA antiarrhythmic agents used to maintain sinus rhythm. Generally, start administration in hospital because of high risk of adverse effects. All patients treated with class IA agents should be treated concomitantly with AV nodal blocking agents. Some patients demonstrate a slowing in atrial rate and an increase in AV conduction with rapid ventricular rates when treated with IA agents alone. Fading as first-line drugs for AF.Drug Name
| Quinidine (Cardioquin, Quinalan, Quinidex, Quinaglute) -- Of Vaughn-Williams class IA agents, only quinidine is FDA-approved for AF. As with all class IA agents, QRS and QTc prolongation are main ECG manifestations. Should not be used in patients with a prolonged QTc baseline (>460 milliseconds). Generally has fallen out of favor as a first- or second-line agent for treatment of AF. |
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| Adult Dose | 300 mg PO q8-12h
324 mg PO q8h of quinidine gluconate formulation| Pediatric Dose | Not established |
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| Contraindications | Prior thrombocytopenic purpura during quinidine administration; complete heart block, unless a ventricular pacemaker is present, long QTc at baseline (>460 milliseconds), history of TdP |
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| Interactions | Slows elimination of digoxin and simultaneously reduces volume of distribution, leading to increased serum digoxin level; potentiates anticoagulant effect of warfarin |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Renal or hepatic dysfunction causes reduction in elimination half-life of parent drug and/or metabolites; CHF causes a reduction in apparent volume of distribution; any of these conditions can result in quinidine toxicity if dosage not appropriately reduced; perform periodic blood counts and liver and kidney tests during long-term therapy; in general, initiate during continuous cardiac monitoring, with careful attention to the QTc interval |
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Drug Name
| Procainamide (Procanbid, Pronestyl) -- Not FDA-approved for treatment of AF; however, many use this agent for acute cardioversion (eg, postoperatively) and because it can be administered IV. Administered IV, useful for acute conversion and can subsequently be converted to oral dose. Negative inotropic agent and vasodilator, and care must be taken in administering to patients with reduced LV function. Generally considered second-line agent. |
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| Adult Dose | 1000-2500 mg PO q12h (Procanbid formulation) based on body weight and normal renal function; not to exceed 18 mg/kg over 1 h with initial infusion
Procainamide and N-acetyl procainamide (NAPA) levels should be drawn after steady state reached| Pediatric Dose | Not established |
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| Contraindications | History of complete heart block, unless a ventricular pacemaker present; lupus erythematosus; TdP; long QTc at baseline (>460 milliseconds) |
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| Interactions | Can expect increased levels of procainamide metabolite NAPA (a class III antiarrhythmic agent) in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine; may increase effect of skeletal muscle relaxants (eg, 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 |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Agranulocytosis rate of 0.5% with 20-25% mortality; weekly CBC counts recommended for first 3 mo and regularly thereafter
Renal clearance; renal insufficiency may lead to accumulations of high plasma levels and its active metabolite, NAPA
In general, initiate during continuous cardiac monitoring, with careful attention to QTc interval |
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Drug Name
| Disopyramide (Norpace) -- Not commonly used to treat AF because has adverse anticholinergic effects and because it is a strongly negative inotropic agent, which may precipitate CHF and cardiogenic shock in patients with reduced LV function. May be useful in vagally mediated syncope. |
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| Adult Dose | 150 mg PO q6h
300 mg PO q12h (CR formulation)| Pediatric Dose | <12 years: 6-20 mg/kg/d PO divided q6h
>12 years: Administer as in adults| Contraindications | Documented hypersensitivity; history of complete heart block; sick sinus syndrome, cardiogenic shock; CHF; prolonged baseline QTc (>460 milliseconds) |
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| Interactions | Phenytoin, rifampin, and phenobarbital may decrease effects; toxicity increases with erythromycin and sparfloxacin; levels of digoxin increase |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Dose adjustments necessary in liver disease, renal disease, and elderly persons; anticholinergic effects can cause urinary retention and blurred vision
In general, initiate during continuous cardiac monitoring, with careful attention to QTc interval |
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Drug Category: Antiarrhythmics, class IC -- Indicated for patients with AF and supraventricular tachycardia without structural heart disease. Given the results of the CAST I and II trials (increased mortality), type IC agents are generally not used in patients with concomitant LV dysfunction and/or CAD. Applicability of CAST results to other populations (eg, patients without recent MI) is uncertain. At present, use is generally unacceptable in patients without life-threatening ventricular arrhythmias, even if patients are experiencing unpleasant, but not life-threatening, symptoms or signs. Many specialists initiate class IC antiarrhythmic agents in an outpatient setting for patients with paroxysmal AF and not associated structural heart disease, awaiting outpatient electrical cardioversion in the near future. Regardless, close patient follow-up is mandated, with frequent ECG monitoring or via transtelephonic monitoring for potential signs of proarrhythmia.Drug Name
| 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. Reduces spontaneous automaticity and depresses triggered activity.
Indicated for documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Appears to be effective in treatment of supraventricular tachycardias, including AF and flutter. Not recommended in patients with 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 Dose | 150-300 mg PO tid
225, 325, 425 mg PO bid (SR formulation)| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity, second- or third-degree AV block, right bundle-branch block associated with left hemiblock (bifascicular block) or trifascicular block; concurrent use of ritonavir or amprenavir |
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| Interactions | Rifampin may decrease plasma levels; quinidine may increase pharmacologic effects; may increase plasma levels of beta-blockers, cyclosporine, warfarin, and digoxin; CYP4502D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in preexisting sinus node dysfunction, history of CHF, post MI, myocardial dysfunction, or sick sinus syndrome (exacerbates sick sinus syndrome and causes sinus pauses or sinus arrest); reserve use for life-threatening arrhythmias only due to deaths associated with proarrhythmic effects of class IC antiarrhythmics; highly metabolized in liver; considerable percentage of metabolites (18-35%) excreted in urine; patients with impaired liver and renal function need careful monitoring for excessive pharmacological effects (adjust dose); rarely, positive ANA titers are reported, are reversible upon cessation of treatment, and may even disappear with continued therapy |
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Drug Name
| Flecainide (Tambocor) -- Blocks sodium channels, producing dose-related decrease in intracardiac conduction in all parts of heart. Increases electrical stimulation of threshold of ventricle, His-Purkinje system. Shortens phase 2 and 3 repolarization, resulting in decreased action potential duration and effective refractory period.
Indicated for treatment of paroxysmal AF/flutter associated with disabling symptoms and paroxysmal supraventricular tachycardias, including AV nodal reentrant tachycardia, AV reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. Also indicated for prevention of documented life-threatening ventricular arrhythmias (eg, 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 Dose | 50-150 mg PO bid |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity, preexisting second- or third-degree AV block, right bundle-branch block associated with left hemiblock (bifascicular block) or trifascicular block), unless a pacemaker is present to sustain cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI |
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| Interactions | May increase toxicity of digoxin; beta-adrenergic blockers, verapamil, and disopyramide may have additive inotropic effects when coadministered; CYP4502D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in preexisting sinus node dysfunction, history of CHF, post MI, myocardial dysfunction, or sick sinus syndrome (exacerbates sick sinus syndrome and causes sinus pauses or sinus arrest); reserve use for life-threatening arrhythmias only due to deaths associated with proarrhythmic effects of class IC antiarrhythmics; adjust dose in renal or hepatic impairment; known to increase endocardial pacing thresholds; may suppress ventricular escape rhythms |
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Drug Category: Antiarrhythmics, class III -- Currently, class III antiarrhythmic agents sotalol and dofetilide are FDA-approved for use in treating atrial arrhythmias; however, amiodarone is also widely used in maintenance of sinus rhythm in patients with AF. Dofetilide is a new agent and must be initiated in an inpatient setting. Sotalol is also initiated in an inpatient setting.Drug Name
| Amiodarone (Cordarone) -- Has antiarrhythmic effects that overlap all 4 Vaughn-Williams antiarrhythmic classes. Has a low risk of proarrhythmia, and any proarrhythmic reactions generally are delayed. Used in patients with structural heart disease. Most clinicians are comfortable with inpatient or outpatient loading with 400 mg PO tid for 1 wk because of low proarrhythmic effect, followed by weekly reductions with goal of lowest dose with desired therapeutic benefit (usual maintenance dose for AF is 200 mg/d). During loading, patients must be monitored for bradyarrhythmias. |
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| Adult Dose | 400 mg PO tid for 1 wk, followed by weekly reductions (goal of lowest dose with desired therapeutic benefit)
Maintenance for AF: 200 mg/d| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity, complete AV block and intraventricular conduction defects; patients taking ritonavir or sparfloxacin |
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| Interactions | Increases effect and blood levels of theophylline, methotrexate, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity is increased by ritonavir and sparfloxacin; coadministration with calcium channel blockers may cause an additive effect and may further decrease myocardial contractility; cimetidine may increase levels |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Pulmonary toxicity has a 3-7% incidence and is dose-related, rare with doses <400 mg/d; gallium scan and lung biopsies confirm diagnosis; discontinuation with administration of steroids is preferred; assess baseline thyroid, liver, and pulmonary functions; perform thyroid and liver studies at regular intervals (6 mo); perform yearly chest radiographs, looking for evidence of pulmonary fibrosis; toxicity and adverse effects are a function of daily dose and duration of therapy, making this drug less desirable in younger populations; use with extreme caution in patients with severe pulmonary disease (can cause pulmonary fibrosis and death); regular ophthalmologist examinations due to rare cases of optic neuritis |
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Drug Name
| Sotalol (Betapace AF) -- Class III agent with beta-blocking effects. Effective in maintenance of sinus rhythm, even in patients with underlying structural heart disease. Inpatient loading is FDA-mandated. |
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| Adult Dose | 80 mg PO bid initially, with therapeutic goal of 120-160 mg PO bid |
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| Pediatric Dose | Not established |
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| Contraindications | Prolonged QTc at baseline (generally >500 milliseconds); history of TdP; reactive airway disease; renal failure; electrolyte abnormalities |
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| Interactions | Class IA antiarrhythmic agents, disopyramide, quinidine, procainamide; other class III agents (amiodarone) can enhance potassium channel blocking effect and should not be given concomitantly |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Risk factors for sotalol-induced TdP (1.5-2%) include impaired renal function (creatinine >1.4), hypokalemia, female sex, slow heart rates, daily dose >320 mg, history of CHF or VT/VF, and QTc >500-525 milliseconds |
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Drug Name
| Dofetilide (Tikosyn) -- Recently approved by FDA for maintenance of sinus rhythm. Has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild to moderate CHF, angina, and either normal or reduced LVEF. No evidence of negative inotropic effect. |
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| Adult Dose | 125-500 mcg PO bid; must be started in a monitored inpatient setting for 3 days by certified clinician
Dose determined by creatinine clearance and QTc response to initial doses| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; CrCl <20 mL/min; QTc >440 milliseconds at baseline and >500 milliseconds after second dose; do not use in conjunction with trimethoprim (either alone or in combination with sulfamethoxazole), verapamil, ketoconazole, cimetidine, megestrol, phenothiazines, TCAs, or prochlorperazine |
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| Interactions | Verapamil, TMP-SMZ, ketoconazole, potassium-depleting diuretics, digoxin, cimetidine, phenothiazines, triamterene, metformin, prochlorperazine, amiloride, megestrol, and antiarrhythmic agents may increase toxicity |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Tightly regulated and can be prescribed only by physicians who register with company, a central distribution pharmacy, and have specific training; to minimize risk of induced arrhythmia, calculations of CrCl and continuous ECG monitoring must be performed; cardiac resuscitation equipment and personnel must be present; maintain potassium levels within reference range prior to and during administration |
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Drug Name
| Ibutilide (Corvert) -- Indicated for conversion of recent-onset AF or atrial flutter (3 h to 90
d). Prolongs repolarization by increasing slow inward sodium current and by blocking delayed rectifier current with rapid onset. |
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| Adult Dose | >60 kg (132 lb): 1 mg IV infusion over 10 min
<60 kg: 0.01 mg/kg IV over 10 min; second infusion of equal strength can be given 10 min after first prn
Magnesium infusion (2 g MgSO4) has been used to pretreat patients receiving ibutilide to prevent TdP| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; history of TdP; concurrent use of other QT prolonging agents |
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| Interactions | Increases toxicity of quinidine and procainamide; concurrent administration with TCAs, phenothiazines, and astemizole (recalled from US market) may prolong QT interval; toxicity of digoxin increases when administered concurrently |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Of 586 patients with recent-onset AF or AFL who received ibutilide, 149 reported medical events related to cardiovascular system, including sustained polymorphic VT (1.7%) and nonsustained polymorphic VT (2.7%); observe patients with continuous ECG monitoring for at least 4 h following infusion or until QTc returns to baseline; skilled personnel and proper equipment (defibrillator and medication for treatment of life-threatening ventricular arrhythmias) must be available during monitoring period
Patients should not be given class IA agents (quinidine, disopyramide, procainamide) or class III drugs (sotalol, amiodarone) concomitantly with or within 4 h postinfusion because of their potential to prolong refractoriness; potential for proarrhythmia exists with other drugs that prolong the QT interval (eg, phenothiazines, TCAs, certain antihistamines); risk of TdP higher if ventricular rate or severely reduced LV function |
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Drug Category: Anticoagulants -- Used to prevent thromboembolic complications.Drug Name
| Heparin -- Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Most data related to use of unfractionated heparin. Low–molecular-weight heparin probably as effective but awaits results from clinical studies. |
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| Adult Dose | 60 U/kg IV initially, followed by maintenance infusion of 12 U/kg/h IV; target aPTT is 50-70 seconds |
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| Pediatric Dose | 50 U/kg IV initially, followed by a maintenance infusion of 15-25 U/kg/h IV; increase dose by 2-4 U/kg/h q6-8h prn, using aPTT results |
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| Contraindications | Documented hypersensitivity, subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia |
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| Interactions | Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, ASA, dextran, dipyridamole, and hydroxychloroquine may increase toxicity |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Bleeding; in neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock |
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Drug Name
| Warfarin (Coumadin) -- Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain INR of 2-3. |
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| Adult Dose | 1-20 mg/d PO qd, adjust dose to desired INR (2-3) for nonvalvular AF/flutter |
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| Pediatric Dose | 0.05-0.34 mg/kg/d PO; adjust dose according to weight and desired INR |
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| Contraindications | Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers; pregnancy, although AHA/ACC guidelines for pregnant patients with mechanical valves mention that risk of thrombotic mechanical valve may be higher than risk of teratogenicity from warfarin |
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| Interactions | Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis |
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FOLLOW-UP
| Section 8 of 11 |
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Further Inpatient Care:
- Monitor INR values of patients on warfarin (desired range 2-3). Note the interaction with amiodarone.
- Monitor patients on antiarrhythmic agents for signs of proarrhythmia. Worsening liver or renal function prompts changes in antiarrhythmic doses and dictates a change in drug. In addition, carefully monitor for changes in heart rate and blood pressure and for CHF. Follow the QTc in patients on type IA and III agents. Unfortunately, proarrhythmia cannot be predicted and can occur despite a normal ECG and normal hepatic and renal function.
- Pacemakers and defibrillators require regular periodic evaluation to ensure proper function.
Further Outpatient Care:
- Because AF tends to be a chronic condition, many authors argue that all patients should be on long-term anticoagulation, especially because many patients may have asymptomatic paroxysms.
- Most follow-up visits include periodic ECG monitoring (especially when taking antiarrhythmics) and Holter monitoring to assess asymptomatic paroxysms and adequate rate control.
Deterrence/Prevention:
- Secondary analysis of placebo-controlled trials using ACE inhibitors and/or ACE receptor blockers in patients with hypertension or in patients with symptomatic heart failure have shown reduced incidence of AF in treatment groups.
- Statins and fish oil preparations may also protect against AF.
Prognosis:
- Based on population data, people in sinus rhythm live longer secondary to a lower incidence of cardiovascular accidents than people in AF. The AFFIRM trial addressed whether rate control and anticoagulation are sufficient goals for asymptomatic, elderly patients. The results showed that medical therapies aimed at rhythm control offered no survival advantage over rate control and anticoagulation.
- Proposed antiarrhythmic drugs of choice for long-term treatment of AF are based on underlying heart disease.
- Structurally normal heart and young age - Propafenone, flecainide, sotalol
- Coronary artery disease - Sotalol, dofetilide, amiodarone
- Congestive heart failure - Amiodarone, dofetilide
- LV hypertrophy (wall thickness >14 mm) - Amiodarone
Patient Education:
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MISCELLANEOUS
| Section 9 of 11 |
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Medical/Legal Pitfalls:
- Because the risk of stroke is 3-8 times higher, properly anticoagulating appropriate patients with warfarin is important. The target INR is 2-3. The addition of drugs, including antiarrhythmics and antibiotics, may cause a rise in the INR in patients with previously stable values.
- Potential medical-legal pitfalls include choosing to not anticoagulate a patient who has significant risk factors and failing to appropriately monitor INR values.
- Use of antiarrhythmic agents requires regular, drug-specific follow-up testing (ie, with dofetilide, regular calculation of creatinine clearance and QTc monitoring; with amiodarone, regular measurement of liver enzymes and thyroid function).
Special Concerns:
- Warfarin is contraindicated during pregnancy.
- Give special consideration to noncompliant patients and patients who are at risk for falling. These patients may be better off with antiplatelet agents such as ASA.
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PICTURES
| Section 10 of 11 |
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