Best Dx/Best Rx: Atrial Fibrillation

Gregory F. Michaud, MD

Harvard Medical School, Boston, MA

Roy M. John, MD, PhD

Harvard Medical School, Boston, MA

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

A supraventricular tachyarrhythmia defined by rapid, irregular atrial activation
Most common sustained arrhythmia
- Incidence ~ 0.1%/yr
- Incidence increases with age (affects one out of 11 persons > 80 yr in U.S.)
- Occurs after 25% of all coronary bypass surgeries and after 60% of combined coronary bypass and mitral valve surgeries
- Independent predictor of mortality and stroke after acute MI
- Life-threatening when associated with Wolff-Parkinson-White syndrome
- May be caused by thyrotoxicity; associated with increased risk of stroke
- High risk of death and stroke when associated with hypertrophic cardiomyopathy
- May be initiated by hypoxia and other metabolic disturbances in pulmonary disease
May occur with other arrhythmias—notably, atrial flutter
Variable clinical manifestations
- Asymptomatic but with irregular pulse
- Stroke
- Palpitations
- Fatigue
- Dyspnea
- Reduced exercise capacity
- Chronic heart failure (CHF)
- Angina
- Presyncope or syncope
- Thromboembolism
- Tachycardia-induced cardiomyopathy

Differential Diagnosis

Classification
- Recurrent: atrial fibrillation (AF) occurring in a patient who has experienced an episode of AF in the past
- Lone: AF occurring in a patient < 60 yr who has no clinical or echocardiographic evidence of cardiopulmonary disease
- Valvular or nonvalvular
  - Valvular: AF in a patient who has evidence or history of rheumatic mitral valve disease or has a prosthetic valve
  - Nonvalvular: all other forms
- Paroxysmal: AF that typically lasts ≤ 7 days and that converts spontaneously to sinus rhythm
- Persistent: AF that typically lasts > 7 days or requires pharmacologic or direct current (DC) cardioversion
- Permanent: AF that is refractory to cardioversion or that has persisted > 1 yr

Best Tests

Laboratory tests
- Thyroid function tests
  - Reassess if ventricular rate difficult to control or if AF recurs unexpectedly after conversion to sinus rhythm
- Serum electrolytes
- Hemoglobin or hematocrit
ECG
- AF verification
- P-wave morphology (atrial flutter)
- Preexcitation
- Atrial arrhythmias other than AF, as possible AF triggers
- Left ventricular hypertrophy (hypertension, hypertrophic cardiomyopathy)
- Bundle branch block or previous MI (coronary artery disease [CAD], left ventricular dysfunction, conduction system disease)
- RR, QRS, QT intervals (to guide arrhythmic drug therapy)
Imaging
- Chest radiography
  - Intrinsic lung disease
  - Abnormal pulmonary vasculature, for pulmonary hypertension
  - Cardiac size and shape (CHF, pericardial disease)
- Transthoracic echocardiography
  - Left and right atrial size and function
  - Left ventricular size, function, and hypertrophy
  - Valvular heart disease, including rheumatic heart disease
  - Right ventricular systolic pressure, for pulmonary hypertension
  - Left atrial thrombus
  - Spontaneous echocardiographic contrast (low sensitivity)
  - Pericardial disease
  - Aortic plaque (low sensitivity)
Additional testing
- Event and Holter monitors
- Documentation of infrequent symptomatic episodes where AF not confirmed previously
- Therapeutic follow-up of rate control
Exercise testing
- Confirm presence of ischemic heart disease
- Unmask exercise-mediated AF
- Evaluate safety of specific medications
- Assess rate control
Transesophageal echocardiography (TEE)
- Establish risk of embolic stroke
  - Left atrial and left atrial appendage thrombus
  - Left atrial and left atrial appendage spontaneous echo contrast
  - Left atrial appendage flow velocity
  - Aortic plaque
Electrophysiologic study
- Define specific forms of AF amenable to catheter-based intervention
- Assess underlying conduction system etiology of wide-complex tachycardias

Best Therapy

Newly Discovered AF

Paroxysmal
- No therapy unless symptoms severe (e.g., hypotension, CHF, angina)
- Anticoagulation as needed
Persistent
- Rate control and anticoagulation as needed
  - Consider antiarrhythmic drug therapy
  - Cardioversion
  - Long-term antiarrhythmic drug therapy unnecessary
- Accept permanent AF
  - Anticoagulation and rate control as needed

Recurrent Paroxysmal AF

Minimal or no symptoms
- Anticoagulation and rate control as needed
- No drug therapy for prevention of AF
Disabling symptoms when in AF
- Anticoagulation and rate control as needed
- Antiarrhythmic drug therapy

Recurrent Persistent AF

Minimal or no symptoms
- Anticoagulation and rate control as needed
Disabling symptoms when in AF
- Anticoagulation and rate control
- Antiarrhythmic drug therapy
- Electrocardioversion as needed
- Continue anticoagulation as needed and therapy to maintain sinus rhythm

Permanent AF

Anticoagulation and rate control as needed

Drug Therapy

Drugs for Cardioversion of Atrial Fibrillation and Maintenance of Sinus Rhythm

Considerations in pharmacologic cardioversion
- Acute conversion rather than rate control if patient hemodynamically unstable with angina, CHF, symptomatic hypotension, acute MI
- Lower success rate than with electrical cardioversion
- Risk of life-threatening arrhythmias
- Efficacy typically declines as duration of AF increases
Considerations in pharmacologic maintenance of sinus rhythm
- Amiodarone and dofetilide first-line therapy in patients with CHF
- Amiodarone first choice if LVH with left ventricular wall thickness ≥ 14 mm
- Sotalol safe for use in patients with implantable cardioverter defibrillators (ICDs)
- Agents with beta-blocking properties preferred in patients with CAD
Follow-up monitoring
- ECG
  - Necessary in all patients on antiarrhythmic medication
  - Exercise ECG within 3 days of starting flecainide or propafenone; monitor for QRS widening
- Serum potassium and magnesium
- Renal function
Amiodarone
- Toxicity: bradycardia, visual disturbances, nausea, constipation, phlebitis (I.V.); hepatic, ocular, pulmonary, thyroid, neurologic toxicity
- Hours to weeks for cardioversion
- Safe in patients with left ventricular dysfunction
- Torsade de pointes (TdP)/ventricular tachycardia (VT) less common than with dofetilide, ibutilide, or sotalol
- Dose for cardioversion
  - Oral, inpatient: 1.2–1.8 g/day in divided doses until 10 g total, then 200–400 mg/day maintenance; or 30 mg/kg single dose
  - Oral, outpatient: 600–800 mg/day in divided doses until 10 g total
  - Intravenous/oral: 5–7 mg/kg over 30–60 min, then 1.2–1.8 g/day continuous I.V. or divided oral doses until 10 g total
- Dose for maintenance of sinus rhythm: 100–400 mg q.d.
  - Cost/mo: $58
Dofetilide
- Days to weeks for cardioversion
- Safe in patients with left ventricular dysfunction
- Dose for cardioversion (for specified creatinine clearance, C_Cr)
  - 500 µg b.i.d. for C_Cr > 60 ml/min
  - 250 µg b.i.d. for C_Cr 40–60 ml/min
  - 125 µg b.i.d. for C_Cr 20–40 ml/min
  - Contraindicated for C_Cr < 20 ml/min
- Dose for maintenance of sinus rhythm: 500–1,000 µg q.d.
  - Dosage adjustment based on corrected QT interval (QT_C)
Ibutilide
- Used for cardioversion only; time to cardioversion: < 1 hr
- Monitor serum potassium and magnesium
- Requires 4 hr of monitoring for TdP
- Safe in patients with left ventricular dysfunction
- Dose: 1 mg I.V. over 10 min; repeat once if necessary
Sotalol (toxicity: bradycardia)
- Used for maintenance of sinus rhythm only
- Use with caution in patients with left ventricular dysfunction
- May exacerbate CHF, COPD
- Associated with TdP
- Dose: 240–320 mg q.d.
  - Dosage adjustment based on QT_c
  - Reduced dose with renal insufficiency
  - Cost/mo: $147
Flecainide
- Time to cardioversion: 3 hr
- Pretreat with AV nodal blocking agents (e.g., verapamil, diltiazem) to avoid accelerated ventricular response
- Avoid in patients with CHF, left ventricular dysfunction, or CAD
- Levels increased by amiodarone
- Dose for cardioversion: 200–300 mg
- Dose for maintenance of sinus rhythm: 200–300 mg q.d.
  - Reduced dose with renal insufficiency
  - Cost/mo: $115
Propafenone
- Toxicity: blurred vision, hypotension
Quinidine
- Toxicity: hypotension, nausea, diarrhea, fever, hepatic dysfunction, thrombocytopenia, hemolytic anemia
Disopyramide
- Toxicity: dry mucous membranes, constipation, urinary retention; significant reduction in left ventricular function
- Time to cardioversion: < 12 hr
- Efficacy for cardioversion of AF reduced or unproven
- Side effects limit use
- Associated with TdP
- Pretreat with AV nodal blocking agents to avoid accelerated ventricular response
- Avoid in patients with CHF or left ventricular dysfunction
- Dose for cardioversion: 200 mg q. 4 hr, up to 800 mg
- Dose for maintenance of sinus rhythm: 400–750 mg q.d.
  - Reduced dose with renal insufficiency
  - Cost/mo: $84
Procainamide
- Toxicity: drug-induced lupus, vasculitides, blood dyscrasias, CNS disturbances
- Time to cardioversion: < 24 hr
- Efficacy for cardioversion of AF low or unproven
- Side effects limit use
- Associated with TdP
- Dose for cardioversion: 100 mg I.V. q. 5 min, up to 1,000 mg
- Dose for maintenance of sinus rhythm: 1,000–4,000 mg q.d.
  - Reduced dose with renal insufficiency or hepatic dysfunction
  - Cost/mo: $64

Drugs for Ventricular Rate Control in Atrial Fibrillation

Goals
- Resting ventricular rate: 60–80 beats/min
- Rate during moderate exercise: 90–115 beats/min
Patient considerations
- Reduced ventricular function
  - Avoid diltiazem, verapamil
  - Beta blockers preferable for acute and long-term rate control
- CAD
  - Beta blockers preferred (reduced mortality)
- High sympathetic tone
  - Digoxin effects attenuated; rarely useful for rate control
- Pulmonary disease
  - Diltiazem and verapamil preferred in patients with asthma
  - Monitor beta blockers carefully in patients with COPD
- Atrial flutter
  - Rate control often difficult to achieve; consider radiofrequency ablation for primary therapy
Esmolol
- I.V. loading dose: 0.5 mg/kg over 1 min
- I.V. maintenance dose: 5–20 mg/kg/min
Metoprolol
- I.V. loading dose: 2.5–5 mg over 2 min, up to 15 mg
- I.V. maintenance dose: bolus q. 4–6 hr
- Oral maintenance dose: 50–200 mg q.d. in divided doses
  - Cost/mo: $14
Propranolol
- I.V. loading dose: 0.15 mg/kg over 1 min, repeat once
- I.V. maintenance dose: bolus q. 4 hr
- Oral maintenance dose: 80–240 mg q.d. in divided doses
  - Cost/mo: $19.50
Diltiazem
- I.V. loading dose: 0.25 mg/kg over 2 min
Verapamil
- I.V. loading dose: 75–150 µg/kg over 2 min
- I.V. maintenance dose: bolus q. 3–6 hr
Digoxin
- I.V. loading dose: 0.25 mg q. 2 hr up to 1.5 mg
- I.V. maintenance dose: 0.125–0.25 mg q.d.
Amiodarone
- I.V. loading dose: 1.2–1.8 g/day until 10 g total
- I.V. maintenance dose: 720 mg/day up to 3 wk

Antithrombotic Therapy in Atrial Fibrillation

Considerations
- Antithrombotic therapy in atrial flutter based on AF guidelines
- Tight monitoring in patients ≥ 75 yr because of increased risk of both stroke and bleeding
- Risk of thromboembolism 1%–5% at cardioversion; consider anticoagulation before, after, or both
- Discontinuance of anticoagulation for elective surgery
  - If no mechanical heart valve, discontinue anticoagulation for up to 1 wk before procedure
  - If mechanical heart valve, discontinue warfarin 1 wk before procedure; continue anticoagulation with intravenous unfractionated heparin
ACC/AHA/ESC recommendations for antithrombotic therapy in AF
- Age < 60 yr, no heart disease (lone AF)
  - Aspirin, 325 mg q.d., or no therapy
- Age < 60 yr, heart disease but no risk factors
  - Aspirin, 325 mg q.d.
- Age ≥ 60 yr but no risk factors
  - Aspirin, 325 mg q.d.
- Age ≥ 60 yr with diabetes mellitus or CAD
  - Warfarin (INR, 2.0–3.0)
  - Consider addition of aspirin, 81–162 mg q.d.
- Age ≥ 75 yr, especially in women
  - Warfarin (INR, 2.0)
- Heart failure
  - Warfarin (INR, 2.0)
- Left ventricular ejection fraction ≤ 0.35
  - Warfarin (INR, 2.0–3.0)
- Thyrotoxicosis
  - Warfarin (INR, 2.0–3.0)
- Hypertension
  - Warfarin (INR, 2.0–3.0)
- Rheumatic heart disease (mitral stenosis)
  - Warfarin (INR, 2.5–3.5, possibly higher)
- Prosthetic heart valves
  - Warfarin (INR, 2.5–3.5, possibly higher)
- Previous thromboembolism
  - Warfarin (INR, 2.5–3.5, possibly higher)
- Persistent atrial thrombus on TEE
  - Warfarin (INR, 2.5–3.5, possibly higher)

Nonpharmacologic Therapy

Electrical Cardioversion of Atrial Fibrillation

DC cardioversion
- Most effective method for achieving sinus rhythm (70%–90% success)
  - Highly effective for cardioversion of atrial flutter (~ 95% success)
- Success rate enhanced by pretreatment with antiarrhythmic drugs: amiodarone, ibutilide, sotalol, flecainide, propafenone, disopyramide, quinidine
- Risks
  - Reprogramming or malfunction of permanent pacemakers or ICDs
  - Life-threatening arrhythmias
- Risk factors for failure
  - Longer duration of AF (particularly > 1 yr)
  - Older age
  - Left atrial enlargement
  - Cardiomegaly
  - Rheumatic heart disease
  - Transthoracic impedance

Nonpharmacologic Approaches to Maintaining Sinus Rhythm in Atrial Fibrillation

Considerations
- Offers benefit of reducing use of antiarrhythmics
- AV nodal ablation with permanent pacemaker insertion an option if rate control not achieved by pharmacologic therapy
- Permanent pacemaker an option in patients with labile response to pharmacologic therapy and symptomatic bradycardia
Catheter-based radiofrequency ablation of ectopic arrhythmic foci
- Success rate in paroxysmal AF > 70%, lower in chronic AF
- Consider as primary therapy for atrial flutter
- Risks: thromboembolism, pulmonary vein stenosis, cardiac perforation
Surgical ablation
- Success rate in eliminating AF > 90%
- Permanent pacemaker required postoperatively in 25% of patients
- In general, consider only if patient undergoing cardiac surgery for other indications
Implantable atrial defibrillators
- Indications
  - Unable to tolerate other strategies of ventricular rate control
  - Condition refractory to pharmacologic and ablative therapies
- Limitations
  - Pain from the electrical shock
  - Risks of implantation (e.g., bleeding, infection)

Best References

Fuster V, et al: J Am Coll Cardiol 38:1231, 2001 PMID 11583910

Hirsh J, et al: J Am Coll Cardiol 41:1633, 2003 PMID 12742309

Prystowsky EN, et al: Circulation 93:1262, 1996 PMID 8653857

The authors have no commercial relationships with manufacturers of products or providers of services discussed in this module.

February 2006