RISK FACTORS: Hypertension, Diabetes mellitus, Left ventricular hypertrophy, Coronary artery disease, Congestive heart failure, Rheumatic heart disease
STROKE IS MAJOR COMPLICATION OF AF. CLINICAL TRIALS HAVE SHOWN THAT ANTICOAGULATION WITH WARFARIN DECREASES THE RISK BY 50-80%
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
o 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.
o 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 reduced LV function.
" Anticoagulation
o 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).
o 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.
o In the future, low-molecular-weight heparins will be used to facilitate initial outpatient anticoagulation until warfarin is therapeutic. Studies are currently being conducted to assess feasibility and safety.
" Long-term prophylaxis
o 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.
" Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III and V trials were trials performed in Europe (SPORTIF III) and in North America (SPORTIF V). Both were noninferiority trials. By definition, noninferiority trials intend to show that an experimental treatment (ximelagatran) does not produce worse results than those of a known active control (warfarin) by a specified margin (2% per year).
" SPORTIF III was reported in The Lancet in November 2003. It was a phase 3, multicenter, randomized, controlled clinical trial that compared warfarin to ximelagatran in the treatment of 3410 subjects with AF and one or more stroke factors. The primary endpoint was stroke or systemic embolism. The primary event rate by intention to treat was 2.3% per year for warfarin and 1.6% for ximelagatran (absolute risk reduction, 0.7%; relative risk reduction, 29%). Rates of disabling or fatal stroke, mortality, and major bleeding were similar, but the rate of combined minor and major hemorrhages was 29.8% per year for warfarin and 25.8% for ximelagatran (relative risk reduction, 14%; P = .007). Raised serum alanine aminotransferase (ALT) levels were more commonly observed in the ximelagatran group.
" SPORTIF V was reported in the American Heart Journal in September 2003 and at the American Heart Association Scientific Sessions in November 2003. This study included a double-blinded treatment allocation with 3922 subjects. Again, the primary endpoints were strokes and systemic embolic events with a noninferiority treatment objective compared with warfarin. The study commenced in July 2000 and enrollment ended in December 2001. Data analysis was extensive and included safety monitoring. The primary event rate by intention to treat was 1.2% per year for warfarin and 1.6% for ximelagatran. The ximelagatran rate was identical in the 2 studies, whereas the rate for warfarin in SPORTIF V was half that noted in SPORTIF III. The reasons for this difference in the warfarin groups continue to be evaluated.
" In both studies, the rates of intracranial and/or other major bleeding events were insignificant. However, when the event rates for major and minor bleeding are combined, ximelagatran was significantly better than warfarin (P <.001 and P <.007, respectively). Elevated ALT levels were noted in SPORTIF III and V and in all previously conducted long-term ximelagatran trials. These elevations are transient, and the levels return to normal regardless of whether the drug is discontinued. It appears that the ALT elevation is limited to the first 6 months of treatment with ximelagatran.
o Patients with no structural heart disease and patients younger than 65 years have lone AF and an extremely low risk for stroke. Generally, they do not need anticoagulation. Aspirin (ASA) at 325 mg/d is recommended.
o 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
o The decision to restore sinus rhythm acutely depends on the hemodynamic status of the patient.
o Consideration of impending hemodynamic collapse or acute cardiac ischemia may influence the decision to cardiovert immediately.
" Elective conversion to sinus rhythm
o 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.
o 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.
o 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 4-6 weeks after sinus rhythm is restored.
" Pacing to prevent AF
o 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.
o In addition, biatrial pacing and dual-site atrial pacing may reduce the prevalence of AF. This is currently an active area of research. Which areas are the best for lead placement (ie, high right atrial, coronary sinus, left atrial sites) remain unknown.
" Atrial defibrillators
o 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.
o Defibrillation energy requirements can be higher than the patient's pain threshold. This can represent a problem in some 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.
o In addition, the next generation of ventricular defibrillators incorporates atrial defibrillation therapies. Patients with reduced LV function and a tendency toward heart failure with episodes of AF will benefit greatly from early conversion to sinus rhythm.
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
o Parallel to the surgical Maze procedure, electrophysiologists are attempting to recreate surgical suture lines with radiofrequency lesions (still investigational).
o 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).
o 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.
o Research currently focuses on catheter designs to deliver linear continuous lesions in both atria.
" Catheter ablation of focal triggers of AF
o In some patients, AF seems to be triggered by foci, usually located within the superior pulmonary veins. These foci can trigger the atria to fibrillate.
o Patients typically have an abundance of ectopic atrial beats noted on 24-hour Holter monitoring. Isolation of the ectopic focus is performed successfully at many centers, and patient selection is key to success.
o 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
o AV node ablation may represent an alternative in patients with chronic AF and an uncontrolled ventricular response despite aggressive medical therapy.
o Catheter ablation of the AV junction permanently interrupts conduction from the atria to the ventricles.
o Because the result is permanent AV block, a permanent pacemaker is required. AF may still exist, but the pacemaker governs the ventricular response.
o The risk of thromboembolism is unchanged, and patients still require anticoagulation; however, most patients are relieved of their symptoms.
o 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.
o Improvements in LV size and function, functional class, and quality-of-life scores have been demonstrated.
Diet:
" Diet restrictions, if any, are as appropriate for the underlying heart disease and any other comorbidities (eg, diabetes mellitus).
MEDICATION :
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 :
1. BETA BLOCKERS :
- PROPRANOLOL
- ATENOLOL
- METOPROLOL
2. ATRIOVENTRICULAR NODAL CONDUCTION BLOCKER:
- DIGOXIN
3. ANTIARRHYTHMICS, CLASS IA :
- QUINIDINE
- PROCAINAMIDE
- DISOPYRAMIDE
4. ANTIARRHYTHMIC, CLASS IC :
- PROPAFENONE
- FLECAINIDE
5. ANTIARRHYTHMICS, CLASS III
- AMIODARONE
- SOTALOL
- DOFETILIDE
- IBUTILIDE
6. ANTICOAGULANTS TO PREVENT THROMBOEMBOLIC COMPLICATIONS :
- HEPARIN
- WARFARIN