section name header

Info


A. Introduction navigator

  1. Most common cardiac arrhythmia affecting ~1.5 to >2 million in USA
    1. Chronic Atrial Fibrillation (CAF)
    2. Paroxysmal Atrial Fibrillation (PAF)
    3. These two types appear to have similar risk factors and complications
    4. Lone AFib (~15% of cases): AFib without underlying heart disease in persons age <55
    5. Lone AFib carries a good prognosis
    6. Familial: multiple genes now implicated [26]
  2. Epidemiology [7]
    1. >2 million persons in USA with AFib
    2. Overall prevalence is ~0.95% in adults aged 20 years or older
    3. Sligh male predominance (1.1% versus 0.8%)
    4. Prevalance 0.1% in adults <55 years
    5. Prevalence ~4% in adults >60 years
    6. Prevalance 9.0% in adults >80 years
    7. Lifetime risk ~25% (has increased as population ages) [26]
  3. Description
    1. Over 300 electrical foci in atria appear to fire in parallel
    2. Thus, atrial contractions are rapid and random
    3. Irregularly irregular heart rhythm due to conducted atrial contractions
    4. Loss of normal atrial contraction compromises ventricular filling
    5. Thrombi (clots) form easily in the abnormally contracting atria
    6. Thrombus formation is particularly prominant in atrial appendage
  4. Complications of AFib [4,5]
    1. Thromboembolic Events - mainly strokes, stroke recurrence [8]
    2. Congestive Heart Failure (CHF) - due to poor left ventricular (LV) output
    3. Syncope - due to poor cardiac output with reduced cerebral perfusion
    4. Patients with AFib have increased mortality, morbidity, and treatment costs
  5. Prevention and proper management of AFib should reduce mortality, morbidity, and costs

B. Risk Factorsnavigator

  1. Age
    1. Primarily a disease of older persons, increasing incidence with higher age
    2. Young persons following stress (caffeine, overexertion, fatigue)
    3. Young persons (usually male) with very high vagal (parasympathetic) tone
  2. Heart Disease 50%
    1. Ischemia (Coronary Artery Disease, CAD) - most common (~25% of all patients)
    2. Mitral valve disease (rheumatic and non-rheumatic) - more common in women
    3. Other valvular disease - aortic disease, tricuspid disease
    4. Pericardial disease - pericarditis, effusion, constriction; post-CABG surgery [69]
    5. Right (or left) atrial enlargement
    6. Diffuse cardiomyopathy
    7. Left ventricular hypertrophy (LVH) [74]
    8. Intracardiac Masses - atrial myxoma, thrombi, metastatic tumors
    9. AFib occurs in ~10% of supraventricular tachycardia (SVT) patients given adenosine
  3. Hypertension (HTN)
    1. Present in ~15%-30 of patients with AFib
    2. Onset of AFib may be related to cardiac ischemia
    3. Overall risk is 1.5-2X for development of AFib in patients with HTN
    4. Elevated pulse pressure (>40mm) also risk for new onset AFib [24]
    5. Increases LVH risk (increases AFib risk as well)
  4. Rheumatic Heart Disease 5%
  5. Pulmonary Disease
    1. Pneumonia; increased with parapneumonic effusion, empyema
    2. Bronchitis
    3. Pulmonary embolism
  6. Alcohol
  7. Endocrinopathy
    1. Hyperthyroidism 2-5% (includes subclinical hyperthyroidism) [25]
    2. Low TSH is risk factor for AFib in age >60years [15]
    3. Cushing's Disease
    4. Pheochromocytoma
  8. Obesity ~1.5X risk for AFib [37]
  9. Medications
    1. Caffeine
    2. Theophylline
    3. Stimulants: amphetamines, cocaine
    4. Pseudoephedrine, epinephrine
    5. Adrenergic agonists - ß-agonists, chronotropic drugs, pheochromocytoma
    6. High doses of nicotine (in nicotine gum or patches) have uncommon AFib association
  10. Cardiac Surgery [11,69]
    1. Post-CABG: ~27-40% of patients
    2. CABG Risks: age, CHF, prior AFib, no ß-blockers
    3. Post-valvular surgery: >50%
  11. Sepsis
  12. Parent with AFib: risk 2-3.5X [9]
  13. Genetic Mutations (Familial AFib)
    1. Mutations in connexin 40 gene (GJA5) in 4 of 15 patients with idiopathic AFib [12]
    2. Mutations causing overexpression of atrial natriuetic peptide (ANP) found in famililal AFib [26]
  14. Unknown (Idiopathic) 25-45%
  15. Mnemonic: "PIRATES"
    1. Pulmonary Disease
    2. Ischemia
    3. Rheumatic Heart Disease
    4. Atrial Myxoma
    5. Thyroid / Theophylline
    6. Ethanol
    7. Sepsis / Stimulants / Surgery

C. Pathophysiology [43]navigator

  1. Mutliple mechanisms have been postulated
    1. Single (or two) circuit re-entry
    2. Multiple circuit (5 or more) re-entry
    3. Rapid local ectopic activity
  2. Impossible to determine which mechanism(s) operating in any given patient
  3. Single (or 2) atrial reentrant circuits with very short cycle lengths
    1. These cycle lengths are short enough so that complete atrial contractions cannot occur
    2. AFib will continue until the circuit disappears and fails to regenerate
  4. Remodelling of atrial circuitry occurs during AFib
    1. Prolonged AFib shorten atrial effective refractory period
    2. This predisposes atria to fibrillate again
    3. The longer AFib continues, the more remodelling occurs
    4. The extent of remodelling determines the extent of refractoriness to conversion of AFib
  5. Antiarrhythmic drugs can terminate and reduce recurrence of AFib
  6. Single circuit mechanism may be more effectively treated with ablation surgery

D. Complicationsnavigator

  1. Hypotension (multifactorial)
    1. Loss of atrial function means that ventricular filling is passive rather than active
    2. Rapid ventricular response does not allow adequate time for filling ventrical
    3. Reduced ventricular compliance due LV hypertrophy further reduces filling
    4. Pulmonary Edema, often acute ("Flash") due increased filling pressures
    5. Chronic CHF
  2. Thrombus Formation (atria or atrial appendage)
    1. Usually occurs after 3 days of AFib
    2. Stroke - most common thrombotic complication, 2.5 -18X increased risk [13]
    3. Stroke associated with AFib appears more severe than non-AFib stroke [60]
    4. Pulmonary Embolism - likely common but asymptomatic in most cases
    5. Myocardial Infarction (rare)
    6. Other emboli - renal artery, distal (digital) emboli; all rare
  3. CAF and PAF have similar risks of thromboembolism [4]
  4. AFib with one additional cardiovascular disease is a very poor prognostic sign [5]
  5. Mortality increased risk ~1.5-2.5X [4,5]

E. Symptoms [1] navigator

  1. Hypotension
  2. Angina
  3. Tachycardia ± Palpitations
    1. Acute onset racing heart
    2. Heart skips beats
  4. Tachypnea
  5. Fatigue, poor exercise tolerance
  6. CHF risk increased ~3X for development in AFib
  7. Stroke (see below)

F. Signs and Evaluationnavigator

  1. Irregularly Irregular Pulse
  2. Heart rate faster than detectable peripheral pulse rate
  3. Blood pressure should be determined
    1. Patients with hypotension (decompensation) are at high risk for serious events
    2. Constant initial monitoring should be considered in new onset AFib
    3. Monitoring is important until therapies can take effect
  4. Differential Diagnosis of Irregularly Irregular Pulse
    1. AFib
    2. Atrial Flutter with Variable Block
    3. Multifocal Atrial Tachycardia (at least 3 distinct P waves present)
    4. Sinus Tachycardia with frequent PAC's (usually not acute onset) or with frequent PVC's
  5. Echocardiography [52,53]
    1. Critical for evaluation of ALL patients with new onset and chronic AFib
    2. Evaluation of LA size and LV function
    3. LA size predicts chronicity and likelihood of cardioversion
    4. LV function and size predicts CHF
    5. Reduced LV function is a strong independent predictor of stroke with AFib
    6. Consider transesophageal echocardiography (TEE) in all patients with unclear onset or >48 hours AFib

G. Treatment Overview [1,2,38,43,52,53,63]navigator

  1. Rate Control
    1. Slow ventricular repsonse rate and reduce risk of embolic disease with anticoagulation
    2. Maintain ventricular response <100 bpm
    3. Overall mortality, event-free survival trends better for rate over rhythm control
  2. Recommend Rhythm Control in Specific Patients
    1. Exercise tolerance better with rhythm control, preferred in younger patients
    2. Symptoms despite rate control
    3. Difficulty achieving rate control
    4. Patients not candidates for anticoagulation
    5. Prevention of atrial remodeling, allowing patients to remain candidates for new therapies
  3. Chronic anticoagulation with adjusted dose warfarin unless contraindicated
  4. Cardioversion for acute AFib with direct electrical current or anti-arrhythmic agents
  5. Pulmonary Vein Ablation (PVA) [36]
    1. Likely more effective than antiarrhythics first line [32,50]
    2. Strongly consider PVA in high-volume centers in selected patients
  6. In patients with AFib and CHF, no differences in outcomes for rate versus rhythm control [23]

H. Slowing the Ventricular Response Rate [1,3] navigator

  1. Summary of AV Nodal Blocking Agents
    1. Calcium Channel Blocking agents: diltiazem or verapamil (IV or PO)
    2. ß-Adrenergic antagonist: esmolol (IV), metoprolol (IV or PO), atenolol (PO)
    3. Digoxin IV - restrict to patients with very low LV ejection fraction (LV EF <25%)
    4. Amiodarone IV - very effective for acute cardioversion, reduces heart rate [35]
    5. Adenosine - produces temporary conversion - useful mainly for diagnosis (AF versus other SVT)
    6. Goal ventricular rate <100 bpm
  2. Contraindications to Slowing Rate with Nodal Blockers
    1. Wide complex tachycardia
    2. Wolff Parkinson White syndrome (WPW)
    3. History of short PR interval
    4. Sick sinus syndrome or High grade (2° and 3°) AV Block
    5. Type 1a Agent may be used alone with WPW/AFib, others
  3. Indications for Electrical Cardioversion
    1. Unstable patients (hypotension, angina, severe CHF)
    2. Failure of other means
    3. Usually requires >100J
    4. Partial AV Nodal Ablation
  4. Diltiazem (Cardizem®)
    1. Rapidly acting IV or oral AV nodal blocking agent
    2. Onset of IV in 3 minutes; 1-3 hour duration of action initially
    3. Little anti-inotropic activity makes useful in low EF states
    4. Dose 20mg initially over 2 min IV, then 25mg/kg IV after 15 minutes if necessary
    5. Maintenance IV infusion at 5-15mg/hr recommended until stabilized
    6. Gradually introduce oral long acting diltiazem (180-300mg controlled release)
  5. Verapamil (Calan®, others)
    1. Potent anti-inotropic activity with strong AV-nodal blocking action
    2. Contraindicated in CHF
    3. 5-10mg IV over 2-3 minutes, may be repeated once 30 minutes later
    4. Maintenance infusion is not reliable
    5. Gradually introduce oral long-acting verapamil (120-240mg qd or bid)
  6. Ca2+ gluconate may be given IV to reduce hypotensive effect of calcium blockers
    1. Little effect on nodal blockade but reduces decrease in blood pressure
    2. Dose: 1-2 amps iv rapid bolus (not calcium chloride !)
    3. Given in emergency setting only
  7. ß-Adrenergic Blocking Agents
    1. Extremely potent agents
    2. Contraindicated in CHF with reduced EF and in COPD
    3. Recommended first line for prevention of AFib for cardiac surgery patients [11]
    4. IV administration is strongly recommended for rapid ventricular response in AFib
    5. Efficacy in rate control and anti-inotropic activity similar to verapamil
  8. Esmolol (Breviblock®)
    1. Very short acting IV agent
    2. Dose 0.5mg/kg IV, may be repeated in 5-15 minutes
    3. Maintenance infusion initially 0.05mg/kg/min, up to 0.20mg/kg/min
    4. Half-life ~10 minutes
    5. No oral form available; recommended oral metoprolol
  9. Metoprolol (Lopressor®)
    1. Initial dose 2.5-5mg IV; may be repeated twice in 2-5 minutes
    2. Maintenance infusion not determined
    3. Follow with low dose, short-acting oral 25mg po bid-qid
    4. Increase dose to 50-200mg total daily long acting formulations
  10. Digoxin [1]
    1. Mechanism of slowing is vagotonic effect (increased parasympathetic stimulation)
    2. Generally ineffective as a single agent with relative high toxicity
    3. Loading Dose 1-1.5 mg (0.25mg q1-q8 hours to total dose); then standard oral qd dosing
    4. Load until desired ventricular response rate is obtained
    5. Only used with reduced EF (<25%) and/or hypotension where inotropic activity needed
    6. Follow blood levels carefully as toxic levels build up rapidly
  11. Catheter Ablation [14,19,20,21]
    1. Partial or complete AV node ablation recommended for certain patients:
    2. Rate not controlled with medications
    3. Patients with poor tolerance or high ventricular response rates (drug refractory)
    4. Also for patients unwilling or unable to use anticoagulation
    5. Patients with CHF and AFib: ablation improves cardiac function, symptoms, quality of life [14]
    6. PVA (see above) may be used first line and appears more effective than anti-arrhythmic agents [32,36]
    7. Complete ablation as safe as medications in lone AFib and with heart disease [20]
    8. Severe pulmonary vein stenosis after older catheter PVA ~5% overall [18]
    9. Dual chamber pacing is preferred over ventricular only [19]

I. Risk of Stroke in AFib [1,5] navigator

  1. CHADS2 index predicts stroke risk with ~80% accuracy in AFib [56]
  2. Framingham Heart Study risk score predicts stroke or death in new onset AFib [68]
  3. Non-Rheumatic Heart Disease
    1. Rate is ~2-3% per year
    2. Overall stroke risk with AFib and no RHD is ~6X increased
    3. Within 1 year after discharge for AFib, stroke risk is ~2.4X increased [13]
  4. Risk Factors for Stroke with AFib [68]
    1. HTN
    2. Organic Heart Disease: CHF and CAD
    3. Increasing Age - probably due to increased atherosclerotic plaques
    4. LV EF <25% even without symptoms
    5. Female sex
    6. Prior stroke
    7. Diabetes
  5. Lone Atrial Fibrillation
    1. Defined as younger (age <55) persons with no disease underlying AFib
    2. Stroke risk <1% per year in most studies
    3. In older patients with lone AFib, ASA may be preferred therapy [3]
  6. Paroxysmal Atrial Fibrillation (PAF) [5]
    1. Risk of stroke appears to be similar to chronic AF
    2. Likely that embolism occurs when patient auto-converts to sinus rhythm
  7. Rheumatic Heart Disease
    1. Stroke rate is highest of all AFib: 5-7% per year
    2. Overall risk with rheumatic hear disease and AFib is 18 old increased
    3. Risk is substantially reduced with warfarin therapy
  8. Atrial Flutter [59]
    1. Increased risk of thromboembolism: 32% over 10 years
    2. In case control study, thromboembolic risk at least as high as for AFib
  9. TEE [55,62]
    1. Detects atrial anomalies in nearly all patients who present with AFib and stroke
    2. Detection of clots with TEE reduces risk of emobolic complications to that level with standard 4 weeks of anticoagulation
    3. If no clot visualized on TEE, patients may be safely cardioverted [54,55]
  10. Subtherapeutic warfarin levels strongly increase risk for stroke [62]

J. Prevention of Embolic Complications [1,27,28]navigator

  1. Current Recommendations for Prevention of Stroke in AFib [3,22,28]
    1. Antithrombotic prophylaxis (lifelong) should be individualized based on risk
    2. Warfarin prophylaxis is recommended in ALL AFib patients at high risk for stroke [22]
    3. Aspirin appears to be adequate for prevention of stroke in low risk AFib patients
    4. Most moderate risk patients should have warfarin INR 2.0-2.5
    5. Patient preferences and risk of side effects must be considered
    6. High stroke risk: valvular AFib, any history of thromboembolism, congenital thrombophilia
    7. High risk: CHF, asymptomatic LVEF <25%, ventricular clots, blood pressure >160mm
    8. Initial rule out of clots with transesophageal echocardiography acceptable [52]
  2. Heparin
    1. After 48-96 hours in AFib, patients should receive heparin
    2. In patients with unclear onset of timing of AFib, initiate heparin early
    3. Goal is APTT of 50-70 seconds
    4. Heparin sc may also be effective (20-30KU qd in divided doses)
    5. Warfarin (coumadin) may be started after 1-2 days of heparin
    6. In patients intolerant to warfarin, consider sc low molecular weight (LMW) heparin
  3. Warfarin Overview [22,61]
    1. Overall decreased risk of stroke ~60%, from 4.5% (no therapy) to 1.4% per year
    2. Effective in all patient groups, including >70 years old
    3. Warfarin should always be considered in elderly including octagenarians with AFib [31]
    4. Warfarin INR 2-3 more effective than warfarin INR 1.2-1.5 + ASA 325mg/d [29]
    5. Warfarin is more effective than standard dose ASA (20-40% risk reduction versus ASA)
    6. Warfarin INR 2-3 more effective than and as safe as 75mg ASA qd in >75 year olds [30]
    7. If cerebral ischemic events with AFib occur, INR 2-4 prevented recurrences without significantly increasing bleeding risk [20]
    8. INR below 2.0 was associated with ~2X increased risk of stroke in AFib [10]
    9. Following successful cardioversion, anticoagulation is maintained for at least 4 weeks
    10. ASA+clopidogrel (Plavix®) is inferior to warfarin for vascular events protection in AFib [73]
  4. Dosing Warfarin (Coumadin®)
    1. Moderate dose warfarin (PT 1.2-1.5X control; INR 2-3) effective for non-rheumatic AFib
    2. Higher dose warfarin (INR 3-4) is required for rheumatic fever-associated AFib
    3. Adjusted dose warfarin is more effective than ASA or low fixed dose warfarin [28]
    4. Should begin treatment with heparin + warfarin x 2-3 days, then discontinue heparin
    5. No significant increases risk of bleeding with moderate dose warfarin (INR 2-3)
    6. Age >85 and INR >3 are risk factors for bleeding [34]
  5. Aspirin (ASA) [29]
    1. In AFib, ASA is always better for stroke prophylaxis than placebo
    2. Warfarin anti-coagulation clearly superior to ASA or clopidogrel for high risk [22,27,28,61]
    3. SAPF III: ASA + lose fixed dose warfarin far less effective than warfarin INR 2-3 [29]
    4. ACTIVE W: ASA+clopidogrel less effective than warfarin INR 2-3 for vascular events prevention [73]
    5. ASA favored in non-valvular AFib patients >65 years without other stroke risks [1]
    6. ASA 160mg/d had same efficacy as LMW heparin for prevention of recurrent stroke in patients with stroke and AFib [33]
    7. Optimal ASA dose unknown
  6. Transesophageal Echocardiography (TEE)
    1. TEE is method of choice for visualization of clots in atria including atrial appendage
    2. Patients with AF and no clots on TEE can safely be cardioverted early
    3. Following cardioversion, 4 weeks of warfarin are recommended
  7. Idraparinux [75]
    1. Idraparinux is a specific factor Xa inhibitor dosed once weekly
    2. Idraparinux compared with warfarin (INR 2-3) was superior on preventing thromboembolism in patients with chronic AFib (70% reduction)
    3. Idraparinux caused 1.1 intracranial bleed / 100 patient-years compared with 0.4/100 with warfarin at 10.7 months but similar rates of death
    4. Risk of bleeding increased in elderly and those with renal impairment

K. Conversion to Normal Sinus Rhythm (NSR) navigator

  1. Consider Restoration of NSR [2,4,6,43]
    1. In general, patients should be on an AV nodal blocker prior to cardioversion (not digoxin)
    2. If unstable vital signs or chest pain, electrical cardioversion is first line
    3. If stable, rate control followed by chemical cardioversion may be used
    4. Patients should be on anticoagulation prior to cardioversion unless unstable
    5. Chemical cardioversion success rates are 25-30% in most cases
    6. Amiodarone, dofetilide, propafenone, sotalol are reasonable [35,52]
    7. Amiodarone superior to sotalol (27% versus 24% cardioversion rate) and longer time to recurrence of AFib (569 versus 428 days) [43,71]
    8. For patients with CAD, amiodarone, dofetilide, sotalol reasonable
    9. Digitalis is not used for AFib, unless it is being used for treatment of CHF
  2. Anticoagulation Prior to Conversion to NSR
    1. In stable patients, anti-coagulation is given for >24 hours prior to conversion
    2. Anti-coagulation should be continued for 2-4 weeks post-cardioversion
    3. Risk of clinical thromboembolic events after cardioversion for AFib of <2 day duration (duration evaluated clinically) is extremely low (<1%)
  3. Detection of Thrombi in Patients with AFib [55,57]
    1. All patients with AFib >2 days duration should receive anticoagulation at diagnosis
    2. TEE is recommended prior to cardioversion to detect thrombi if AFib duration >2 days [57]
    3. TEE has ~86% positive predictive value, 100% negative predictive value for detection of left atrial thrombi in patients with AFib
    4. Cardioversion after negative TEE associated with <0.25% risk of thrombotic event [57]
    5. If TEE shows no clot, then patient may be cardioverted safely [54,55]
    6. Anticoagulation should be continued 2-4 weeks after cardioversion
  4. Direct Current Cardioversion
    1. Effective ~85% of patients (>90% for first cardioversion) at 200J-300J
    2. Initial elective cardioversion recommended at 360J due to higher efficacy rates
    3. Newer devices deliver biphasic waveform shocks and require less energy [1]
    4. Combination of cardioversion with an anti-arrhythmic agent increases success rates
    5. Class III (and some Class I) anti-arrhythmic agents are typically used
    6. Ibutilide enhances efficacy of cardioversion, particularly in patients resistant to maintaining sinus rhythm, and in patients who fail initial cardioversion [39]
    7. Calcium blockers and ß-blockers should be continued throughout cardioversion
    8. Digitalis should be held for >24 hours prior to cardioversion
    9. Cardioversion less likely if atrium >5cm or AFib >12 months or failed prior cardioversion
    10. Maintenance of sinus rhythm after cardioversion was 42% at 1 year, 27% at 4 years
    11. Internal cardioversion is associated with >75% success in those who failed trans- thoracic cardioversion, but requires special techniques and equipment [39]
    12. For patients with CAF or PAF and Ventricular Arrhythmias, implantable cardioverter defibrillators (ICD) can detect and terminate many episodes of AFib [19,40]
  5. Hemodynamic and Cardiac Effects of Cardioversion [41]
    1. Gradual increase in cardiac output of ~55% over 4 weeks; up to ~65% at 20 months
    2. After cardioversion, ~30% have a reduction in cardiac output lasting up to 7 days
    3. Acute pulmonary edema following cardioversion occurs in <5% of patients
    4. May be related to pulmonary emboli and/or severe LV shock following cardioversion
    5. Due to variable left and right atrial function, anticoagulation is maintained for >4 weeks
  6. Maintentance of NSR [2,6,42]
    1. Rhythm and rate control have similar long-term outcomes, but NSR generally better for exercise tolerance
    2. Amiodarone (loading dose then 200mg qd) is superior to sotalol and has similar rates of adverse events [71]
    3. One Year NSR with CAF: no treatment 25%; current anti-arrhythmics 40-65%
    4. Dronedarone, related to amiodarone with reduced toxicity, increased NSR duration [44]
    5. Presence of AFib for >36 months, Class III CHF, age >56 yrs associated with reduction in maintenance of NSR
    6. Radiofrequency ablation (RFA) or Maze III surgery may be effective
    7. In patients with CAF, RFA of left atrium during mitral valve surgery increases rate of NSR (44% versus 4% in control group) [72]
    8. Rare complication of atrial-esophageal fistula occurs after RF ablation, presents with sepsis, neurologic symptoms [17]
  7. Drug Selection in CAF or PAF [1,2,6,32]
    1. Lone AFib: propafenone, flecainide [45]; then sotalol, disopyramide, amiodarone, dofetilide
    2. CAD without CHF: amiodarone, sotaolol, dofetilide, disopyramide
    3. CHF or LV EF <35%: amiodarone, dofetilide; avoid flecainide, propafanone
    4. Hypertrophic Cardiomyopathy: amiodarone; then disopyramide, sotalol
  8. Implantable Devices in AFib [19]
    1. AV nodal ablation with pacemaker (dual pacing preferred; see above)
    2. Dual site atrial pacing may prevent recurrent AFib in PAF
    3. Overdrive pacing and atrial defibrillation also appear to reduce PAF events
  9. The high morbidity, mortality and costs of AFib should be reduced by maintaining NSR [4]

L. Specific Antiarrhythmic Agents [1] navigator

  1. Intravenous (IV) Amiodarone (Cordarone®) [35]
    1. IV loading 5mg/kg over 48 hours provides efficacy equal to quinidine given orally
    2. Followed by oral amiodarone, 400mg/d for 7-14 days, then 200mg per day
    3. At 9 months, 67% of patients with AFib on amiodarone were in NSR
    4. Amiodarone IV must be given through a central venous line or causes severe phlebitis
  2. Oral Amiodarone [2,42]
    1. Promotes spontaneous conversion of AF to NSR as well as NSR maintenance
    2. May be used with AFib cardioversion in cases which have failed standard cardioversion
    3. Maintained NSR in 65% of patients after >16 months
    4. Long term toxicity is minimal with 200mg qd maintenance dose
    5. Loading is typically 400mg bid for 14 days, then 400mg qd for 2 weeks
    6. Followed by maintenance dose of 200mg qd or for smaller patients, 100mg qd
    7. Interacts with warfarin (reduce dose 25%) and digoxin (discontinue if possible)
  3. Sotalol (Sotacor®, betapace®) [42]
    1. Maintained NSR in ~30% at 16 months
    2. Initial dose 80mg po bid, titrate slowly (QTc effects) to maximum 240mg bid
    3. In AFib, better tolerated than oral amiodarone but with reduced efficacy [46]
    4. Sotalol may be considered in patients with amiodarone intolerance
    5. May be used in patients with CAD but not CHF as has anti-inotropic activity
    6. QTc prolongation / Torsade risk; carefully monitor QTc
  4. Ibutilide (Corver®) [47]
    1. Class III agent for IV injection, for rapid conversion of AFib, atrial flutter
    2. Conversion with 1mg IV ibutilide was ~35% in AFib, ~60% in flutter
    3. Enhances efficacy of cardioversion, particularly in patients resistant to maintaining NSR, and in patients who fail initial cardioversion [39]
    4. Prolongs QTc in a dose-dependent manner; return to baseline QTc after 2-6 hours
    5. In women, QTc prolongation by ibutilide is affected by stage of menstrual cycle [48]
    6. Dose is 1mg for patients >60kg, 0.01mg/kg for <60kg, IV over 10 minutes; repeat x 1
  5. Dofetilide (Tikosyn®) [49]
    1. Class III agent orally available with good efficacy for AFib cardioversion [58]
    2. Improves rate of cardioversion, spontaneous conversion, and maintenance of NSR
    3. No anti-inotropic activities, even with markedly reduced LV EF
    4. As effective as sotalol without the inotropic effects
    5. Main side effect is increase in QTc interval, increased risk of torsade des pointes (TDP)
    6. Safe in patients with AFib and moderate to severe CHF or CAD [2]
  6. Propafenone [2]
    1. Type Ic agent with up to 75% conversion after single oral dose
    2. Propafenone maintained NSR in 35% of patients after >16 months [42]
    3. Useful in young persons with lone AFib
    4. May be used by patients as needed [45]
  7. IV Procainamide
    1. Restoration of sinus rhythm in patients with Atrial Fibrillation recent onset
    2. Success rate lower than that for cardioversion
    3. Dose: 20mg iv q minute to 1 gm loading, then give orally qid (500-750 mg)
    4. QTc checked prior to each dose (concern >25% increase; stop agent if >50% increase)
    5. Hypotension may occur during IV load; BP monitored q30 min during and 1hr post IV
    6. Prolonged QTc with increased risk of TDP is major concern
    7. Lupus-like syndrome occurs with prolonged (>1 month) use
  8. Quinidine [51]
    1. Increasing concern that chronic quinidine increases mortality
    2. May be reasonable initial therapy for conversion, then consider other agents
    3. Quinidine should now be reserved for second or third line therapy in AFib
    4. Sotalol is better tolerated and amiodarone (low dose) is more effective
  9. Flecainide, a type Ic agent, is effective in persons without ischemic cardiac disease [2,45]

References navigator

  1. Page RL. 2004. NEJM. 351(23):2408 abstract
  2. Zimetbaum P. 2007. NEJM. 356(9):935 abstract
  3. Singer DE. 2003. JAMA. 290(16):2182 abstract
  4. Stewart S, Hart CL, Hole DJ, McMurray JJV. 2002. Am J Med. 113(5):359 abstract
  5. Vidaillet H, Granada JF, Chyou PH, et al. 2002. Am J Med. 113(5):365 abstract
  6. Zimetbaum P and Josephson ME. 2004. Ann Intern Med. 141(9):720 abstract
  7. Go AS, Hylek EM, Phillips KA, et al. 2001. JAMA. 285(18):2370 abstract
  8. Penado S, Cano M, Acha O, et al. 2003. Am J Med. 114(3):206 abstract
  9. Fox CS, Parise H, D'Agostino RB, et al. 2004. JAMA. 291(23):2851 abstract
  10. Hylek EM, Go AS, Chang Y, et al. 2003. NEJM. 349(11):1019 abstract
  11. Maisel WH, Rawn JD, Stevenson WG. 2001. Ann Intern Med. 135(12):1061 abstract
  12. Gollob MH, Jones DL, Krahn AD, et al. 2006. NEJM. 354(25):2677 abstract
  13. Frost L, Engholm G, Johnsen S, et al. 2000. Am J Med. 108(1):36 abstract
  14. Hsu LF, Jais P, Sanders P, et al. 2004. NEJM. 351(23):2373 abstract
  15. Biondi B, Palmieri EA, Lombardi G, Fazio S. 2002. Ann Intern Med. 137(11):904 abstract
  16. Hohnloser SH, Kuck KH, Lilienthal J. 2000. Lancet. 356(9244):1789 abstract
  17. Cummings JE, Schweikert RA, Saliba WI, et al. 2006. Ann Intern Med. 2006. 144(8):572 abstract
  18. Saad EB, Marrouche NF, Saad CP, et al. 2003. Ann Intern Med. 138(8):634 abstract
  19. Cooper JM, Katcher MS, Orlov MV. 2002. NEJM. 346(26):2062 abstract
  20. Ozcan C, Jahangir A, Friedman PA, et al. 2001. NEJM. 344(14):1043 abstract
  21. Catheter Ablation of Atrial Fibrillation. 2004. Med Let. 46(1187):59 abstract
  22. Hart RG, Pearce LA, Agullar MI. 2007. Ann Intern Med. 146(12):857 abstract
  23. Roy D, Talajic M, Nattel S, et al. 2008. NEJM. 358(25):2667 abstract
  24. Mitchell GF, Vasan RS, Keyes MJ, et al. 2007. JAMA. 297(7):709 abstract
  25. Cappola AR, Fried LP, Arnold AM, et al. 2006. JAMA. 295(9):1033 abstract
  26. Hodgson-Zingman DM, Karst ML, Zingman LV, et al. 2008. NEJM. 359(2):158 abstract
  27. Hart RG, Benavente O, McBride R, Pearce LA. 1999. Ann Intern Med. 131(7):492 abstract
  28. Hart RG, Halperin JL, Pearce LA, et al. 2003. Ann Intern Med. 138(10):831 abstract
  29. SPAF III Investigators. 1996. Lancet. 348:633 abstract
  30. Mant J, Hobbs FD, Fletcher K, et al. 2007. Lancet. 370(9586):493 abstract
  31. Gage BF, Fihn SD, White RH. 2001. Ann Int Med. 134(6):465 abstract
  32. Wazni OM, Marrouche NF, Martin DO, et al. 2005. JAMA. 293(21):2634 abstract
  33. Berge E, Abdelnoor M, Nakstad PH, Sandset PM. 2000. Lancet. 355(9211):1205 abstract
  34. Fang MC, Chang Y, Hylek EM, et al. 2004. Ann Intern Med. 141(10):745 abstract
  35. Letelier LM, Udol K, Ena J, et al. 2003. Arch Intern Med. 163:777 abstract
  36. Oral H, Pappone C, Chugh A, et al. 2006. NEJM. 354(9):935
  37. Wang TJ, Parise H, Levy D, et al. 2004. JAMA. 292(20):2471 abstract
  38. Lip GY and Tse HF. 2007. Lancet. 370(9587):604 abstract
  39. Oral H, Souza JJ, Michaud GF, et al. 1999. NEJM. 340(24):1849 abstract
  40. Glikson M and Friedman PA. 2001. Lancet. 357(9262):1107 abstract
  41. Upshaw CB Jr. 1997. Arch Intern Med. 157(10):1070 abstract
  42. Roy D, Talajic M, Dorian P, et al. 2000. NEJM. 342(13):913 abstract
  43. Nattel S and Opie LH. 2006. Lancet. 367(9506):262 abstract
  44. Singh BN, Connolly SJ, Crijns HJ, et al. 2007. NEJM. 357(10):987 abstract
  45. Alboni P, Botto GL, Baldi N, et al. 2004. NEJM. 351(23):2384 abstract
  46. Kochiadakis GE, Igoumenidis NE, Marketou ME, et al. 2000. Heart. 84:251 abstract
  47. Ibutilide. 1996. Med Let. 38(972):38 abstract
  48. Rodriguez I, Kilborn MJ, Liu XK, et al. 2001. JAMA. 285(10):1322 abstract
  49. Dofetilide. 2000. Med Let. 42(1078):41 abstract
  50. Pappone C, Augello G, Sala S, et al. 2006. J Am Coll Cardiol. 48(11):2340 abstract
  51. Grace AA and Camm AJ. 1998. NEJM. 338(1):35 abstract
  52. Snow V, Weiss KB, LeFevre M, et al. 2003. Ann Intern Med. 139(12):1009 abstract
  53. McNamara RL, Tamariz LJ, Segal JB, Bass EB. 2003. Ann Intern Med. 139(12):1009
  54. Klein AL, Grimm RA, Murray D, et al. 2001. NEJM. 344(19):1411 abstract
  55. Silverman DI and Manning WJ. 2001. NEJM. 344(19):1468 abstract
  56. Gage BF, Waterman AD, Shannon W, et al. 2001. JAMA. 285(22):2864 abstract
  57. Weigner MJ, Thomas LR, Patel U, et al. 2001. Am J Med. 110(9):694 abstract
  58. Singh S, Zoble RG, Yellen L, et al. 2000. Circulation. 102:2385 abstract
  59. Halligan SC, Gersh BJ, Brown RD Jr, et al. 2004. Ann Intern Med. 140(4):265 abstract
  60. Penado S, Cano M, Acha O, et al. 2002. Am J Med. 112(7):572 abstract
  61. Van Walraven C, Hart RG, Singer DE, et al. 2002. JAMA. 288(19):2441 abstract
  62. Malouf JF, Ammash NM, Chandrasekaran K, et al. 2002. Am J Med. 113(7):587 abstract
  63. Falk RH. 2002. NEJM. 347(23):1883 abstract
  64. AFFIRM Investigators. 2002. NEJM. 347(23):1825 abstract
  65. Van Gelder IC, Hagens VE, Bosker HA, et al. 2002. NEJM. 347(23):1834 abstract
  66. SPORTIF III Investigators. 2003. Lancet. 362(9397):1691 abstract
  67. Glikson M and Freidman PA. 2001. Lancet. 357(9262):1107 abstract
  68. Wang TJ, Massaro JM, Levy D, et al. 2003. JAMA. 290(8):1049 abstract
  69. Mathew JP, Fontes ML, Tudor IC, et al. 2004. JAMA. 291(14):1720 abstract
  70. SPORTIF V Executive Steering Committee. 2005. JAMA. 293(6):690 abstract
  71. Singh BN, Singh SN, Reda DJ, et al. 2005. NEJM. 352(18):1861 abstract
  72. Doukas G, Samani NJ, Alexiou C, et al. 2005. JAMA. 294(18):2323 abstract
  73. ACTIVE Writing Group. 2006. Lancet. 367(9526):1903 abstract
  74. Okin PM, Wachtell K, Devereux RB, et al. 2006. JAMA. 296(10):1242 abstract
  75. Amodeus Investigators. 2008. Lancet. 371(9609):315 abstract