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REF:  ACP Medicine  Best Dx/Best Rx 2006  |  Afib_rate 2010.pdf  | AnticoagulationRx_AtrialFib 2011.pdf   Atrial Fibrillation Anthony Aizer, M.D., Valentin Fuster, M.D., Ph.D. - Mount Sinai School of Medicine Definition/Key Clinical Features Differential Diagnosis Best Tests Best Therapy   A.  Drugs for Cardioversion  | Amiodarone for Atrial Fib 2007 B.  Drugs for Rate Control C.  Drugs for Antithrombotic 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 less than 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      1.  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 2.  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 3.  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 4.  Permanent AF Anticoagulation and rate control as needed Drug Therapy        A.  Drugs for Cardioversion B.  Drugs for Rate Control C.  Drugs for Antithrombotic Therapy A.  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, CCr) 500 µg b.i.d. for CCr > 60 ml/min 250 µg b.i.d. for CCr 40–60 ml/min 125 µg b.i.d. for CCr 20–40 ml/min Contraindicated for CCr < 20 ml/min Dose for maintenance of sinus rhythm: 500–1,000 µg q.d. Dosage adjustment based on corrected QT interval (QTC) 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 QTc 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 Time to cardioversion: < 6 hr Efficacy reduced in patients with structural heart disease Increases digoxin and warfarin levels Pretreat with AV nodal blocking agents to avoid accelerated ventricular response Avoid in patients with CHF, left ventricular dysfunction, or CAD May exacerbate COPD Dose for cardioversion Oral: 450–600 mg I.V.: 1.5–2.0 mg/kg over 10–20 min Dose for maintenance of sinus rhythm: 450–900 mg q.d. Reduced dose with hepatic dysfunction Cost/mo: $198 Quinidine Toxicity: hypotension, nausea, diarrhea, fever, hepatic dysfunction, thrombocytopenia, hemolytic anemia Time to cardioversion: 2–6 hr Safety concerns limit use in cardioversion; side effects and drug interactions 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 Oral: 0.75–1.5 g in divided doses over 6–12 hr I.V.: 1.5–2.0 mg/kg over 10–20 min Dose for maintenance of sinus rhythm: 600–1,500 mg q.d. Cost/mo: $77 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 B.  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 I.V. maintenance dose: 5–15 mg/hr Oral maintenance dose: 120–360 mg q.d. in divided doses Cost/mo: $20 Verapamil I.V. loading dose: 75–150 µg/kg over 2 min I.V. maintenance dose: bolus q. 3–6 hr Oral maintenance dose: 120–360 mg q.d. in divided doses Cost/mo: $15 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. Oral loading dose: 0.25 mg q. 2 hr up to 1.5 mg Oral maintenance dose: 0.125–0.25 mg q.d. Cost/mo: $9 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 Oral loading dose: 800 mg/day × 1 wk, 600 mg/day × 1 wk, 400 mg/day × 4–6 wk Oral maintenance dose: 200 mg q.d Cost/mo: $29 C.  Antithrombotic Therapy in Atrial Fibrillation        Considerations Antithrombotic therapy in atrial flutter based on AF guidelines Tight monitoring in patients e 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 d 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

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