Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterised by irregularly irregular ventricular pulse and loss of association between the cardiac apex beat and radial pulsation. ¹ Loss of active ventricular filling is associated with:

• Stagnation of blood in the atria leading to thrombus formation and a risk of embolism, increasing the risk of stroke.
• Reduction in cardiac output (especially during exercise) which may lead to heart failure.

• Acute: Onset within the previous 48 hours.
• Paroxysmal: Spontaneous termination within 7 days and most often within 48 hours. Paroxysmal AF may degenerate into a sustained form of AF.
• Recurrent:
  • Two or more episodes, which may be defined as paroxysmal if they terminate spontaneously or persistent if the arrhythmia requires electrical or pharmacological cardioversion for termination.
  • Successful termination of AF does not alter the classification of persistent AF.
• Persistent: Not self-terminating; lasting longer than 7 days or prior cardioversion. Persistent AF may degenerate into permanent AF.
• Permanent:
  • Long-standing AF (defined as over a year) that is not successfully terminated by cardioversion, when cardioversion is not pursued or has relapsed following termination.
  • Reversion of permanent AF to normal sinus rhythm is possible, particularly in those cases where the AF is caused by an underlying disease process which is successfully treated (e.g. thyroid disease) or where a specialist procedure is performed that modifies the electrophysiological properties of the heart.

• Prevalence is approximately 1% of the population.³
• The prevalence of atrial fibrillation rises with age from 1.5% in people in their 60s to more than 10% in those over 90 years old.⁴
• More common in males than females.

• Idiopathic ('lone') atrial fibrillation: 5-10% of patients (diagnosis of exclusion with no evidence of any specific underlying cause)
• Hypertension: especially with associated left ventricular hypertrophy
• Coronary artery disease
• Valvular heart disease, especially mitral valve stenosis
• Cardiac surgery
• Myocarditis
• Atrial septal defect
• Atrial myxoma
• Sick sinus syndrome
• Pre-excitation syndromes with accessory conduction pathways, e.g. Wolff-Parkinson-White syndrome
• Dilated and hypertrophic cardiomyopathy
• Pericardial disease, e.g. pericardial effusion, constrictive pericarditis
• Hyperthyroidism
• Acute infections, especially pneumonia in the elderly
• Acute excess alcohol intake or chronic excess alcohol intake
• Respiratory: lung cancer, chronic obstructive pulmonary disease, pleural effusion, pulmonary embolism, pulmonary hypertension
• Other causes include obesity. sleep apnoea, haemochromatosis, sarcoidosis, and narcotic abuse
• Genetic: autosomal dominant (rare)

Clinical presentation is very variable between being asymptomatic and causing severe heart failure:

• Asymptomatic in up to 20% of patients: detected as an irregularly irregular pulse rhythm with the cardiac apex rate exceeding the wrist pulse rate, or found incidentally on an ECG.
• Manual pulse palpation should be used to assess an irregular pulse indicating underlying AF in patients who present with breathlessness, palpitations, syncope or dizziness, chest discomfort, stroke or TIA (transient ischaemic attack).²
• Palpitations: paroxysmal or persistent.
• Heart failure, lethargy, fatigue, dyspnoea, chest pain, dizziness.
• Syncope is rare unless patient has sick sinus syndrome or Wolff-Parkinson-White syndrome.
• Arterial pulse is irregularly irregular in rhythm, rate and volume.
• First heart sound is of variable loudness.
• Absent 'a' waves in jugular venous pulse.
• Apical-radial pulse mismatch develops when the rate is rapid.

• Atrial flutter
• Atrial extrasystoles
• Supraventricular tachyarrhythmias
• Atrioventricular nodal re-entrant tachycardia
• Wolff-Parkinson-White syndrome
• Ventricular tachycardia

Further assessment is focused on identifying any underlying cause and assessment of cardiac function:

• Electrocardiogram:
  • An ECG is diagnostic except in paroxysmal atrial fibrillation between attacks. Distinguishing feature of atrial fibrillation is variability in the R-R intervals.
  • An ECG should be performed in all patients, whether symptomatic or not, with an irregular pulse in whom AF is suspected.²
  • If paroxysmal AF is suspected and has not been detected by standard ECG recording, a 24-hour ambulatory ECG monitor should be used if asymptomatic episodes are suspected or if episodes are less than 24 hours apart.²
  • An event recorder ECG should be used where symptomatic episodes are more than 24 hours apart.²
• Blood tests: Thyroid function tests, full blood count (anaemia may precipitate heart failure), renal function and electrolytes (abnormal serum potassium levels can potentiate arrhythmias, especially if the patient is taking, or about to start, digoxin), liver function tests and coagulation screen (pre-warfarin).
• Chest x-ray:
  • May indicate cardiac structural causes of atrial fibrillation such as mitral valve disease.
  • May indicate heart failure.
• Echocardiogram:
  • Transthoracic echocardiography (TTE) should be used:²
    • If a baseline echocardiogram is important for long-term management (e.g. in younger patients).
    • If considering a rhythm-control strategy that includes electrical or pharmacological cardioversion.
    • If suspect underlying structural or functional heart disease (failure or murmur) that would influence management, such as choice of antiarrhythmic drug.
    • When needed to help with stratifying stroke risk for antithrombotic therapy, but only where clinical evidence is needed of left ventricular (LV) dysfunction or valve disease.
  • Transoesophageal echocardiography (TOE) should be used:²
    • When TTE has shown an abnormality such as valve disease that needs further assessment.
    • To exclude cardiac abnormalities and TTE is technically difficult or of poor quality.
    • If considering TOE-guided cardioversion.
• CT or MRI scan of the brain: Should be performed if there is any suggestion of stroke or transient ischaemic attack.²

• Atrial fibrillation is often associated with other arrhythmias, e.g. atrial flutter or atrial tachycardia.
• Atrial fibrillation can alternate with atrial flutter, atrial flutter may develop into atrial fibrillation and atrial flutter may occur during treatment of atrial fibrillation with antiarrhythmic drugs.
• In patients with Wolff-Parkinson-White syndrome, atrial fibrillation can lead to rapid ventricular rates and ventricular fibrillation, especially when AV nodal blocking agents are used.

• The management of atrial fibrillation involves control of the arrhythmia (by rhythm or rate control) and thromboprophylaxis to prevent strokes.
• Treat any underlying cause, e.g. acute infection, hyperthyroidism. Atrial fibrillation may revert on treatment or resolution of an associated problem, e.g. acute infection or alcohol intoxication.
• No further intervention may be required, other than lifestyle changes, such as avoiding the precipitating factor, e.g. alcohol or caffeine.
• Treat associated heart failure.

Cardioversion

• With appropriate anticoagulation, DC cardioversion is safe (thromboembolism in less than 1%) and effective in both atrial fibrillation (80-80% success rate) and atrial flutter (success rate over 95%).
• Pharmacological cardioversion:
  • Oral amiodarone is effective in converting atrial fibrillation to normal sinus rhythm and is also the most effective in preventing relapse after cardioversion, but has significant side effects and can enhance the anticoagulant effect of warfarin.
  • Flecainide and propafenone are also recommended but should not be used in patients with structural heart disease, coronary heart disease, left ventricular dysfunction or severe left ventricular hypertrophy.³
  • Patients with structural heart disease are more susceptible to severe complications from pharmacological cardioversion.⁵
  • Recommended drugs for maintaining sinus rhythm are amiodarone, disopyramide, flecainide and propafenone.
• Indications for cardioversion:
  • Recent onset atrial fibrillation (but not always clear when it started)
  • No structural heart disease
  • Successful treatment of precipitating cause, e.g. thyrotoxicosis, chest infection
  • Young age - but elderly are not excluded
  • Acute AF with severe hypotension, acute heart failure, acute myocardial infarction or unstable angina - need urgent cardioversion
• Patients unsuitable for cardioversion include those with:
  • Structural heart disease (e.g. large left atrium >5.5 cm, mitral stenosis) that precludes long-term maintenance of sinus rhythm.
  • A long duration of AF (usually >12 months).
  • A history of multiple failed attempts at cardioversion and/or relapses, even with concomitant use of antiarrhythmic drugs or non-pharmacological approaches.
  • An ongoing but reversible cause of atrial fibrillation (e.g. thyrotoxicosis).
• Electrical versus pharmacological cardioversion: If onset of AF was up to 48 hours previously, either pharmacological or electrical cardioversion can be used. For those with more prolonged AF, electrical cardioversion should used.
• For cardioversion using an intravenous antiarrhythmic agent in patients with persistent AF: Use a Class 1c drug (e.g. flecainide or propafenone) in the absence of structural heart disease, or amiodarone in the presence of structural heart disease.
• Electrical cardioversion with concomitant antiarrhythmic drugs: When patients with AF are to undergo elective electrical cardioversion and there is increased concern about successfully restoring sinus rhythm (e.g. previous failure to cardiovert or early recurrence of AF), concomitant amiodarone or sotalol (a non-cardioselective beta-blocker with additional class III anti-arrhythmic activity) should be given for at least 4 weeks before the cardioversion.
• Transoesophageal echocardiography-guided cardioversion: In patients with AF of greater than 48 hours’ duration, in whom elective cardioversion is indicated:
  • Both TOE-guided cardioversion and conventional cardioversion are equally effective.
  • A TOE-guided cardioversion strategy should be considered if experienced staff and appropriate facilities are available, and when a minimal period of precardioversion anticoagulation is indicated due to patient choice or bleeding risks.

Rate control

• Ventricular rate control may be at least as effective as restoration of sinus rhythm in terms of survival and symptom control, especially in elderly patients.^6,7,8,9,10
• With rate control, the target ventricular rate (measured on an ECG or at the ventricular apex, but not the wrist) is below 80 per minute at rest and 90-115 on moderate exercise.
• A heart rate-limiting calcium-channel blocker (e.g verapamil or diltiazem) or a beta-blocker are recommended as first-line therapy for control of the ventricular rate.² Verapamil should not be combined with a beta-blocker because of the risk of heart block and asystole. Sotalol should not be used just for rate control because it is associated with an increased incidence of ventricular arrhythmias.³
• Digoxin may control the resting heart rate, but rarely adequately controls heart rate during exertion and so should only be considered as monotherapy in predominantly sedentary patients.²
• Digoxin is still considered as initial therapy in patients with heart failure due to left ventricular systolic dysfunction, but these patients should still receive a beta-blocker later.
• Often a combination of two drugs may be needed and, in this case, digoxin can be combined with either a rate-limiting calcium-channel blocker or a beta-blocker.

Other management options

• Pacemaker: In patients with paroxysmal atrial fibrillation in whom medical therapy has failed, atrial overdrive pacing has been shown to decrease recurrent episodes of atrial fibrillation.
• Percutaneous radiofrequency ablation is a treatment option for symptomatic patients with atrial fibrillation refractory to anti-arrhythmic drug therapy or where medical therapy is contraindicated because of co-morbidity or intolerance.¹¹
  • Radiofrequency ablation does not remove the need for anticoagulation or improve mortality.
  • Radiofrequency ablation of the atria can be performed via a catheter introduced through a femoral vein or by surgical radiofrequency ablation in patients undergoing concomitant open-heart surgery.¹²
• Cryoablation or high-intensity focused ultrasound (HIFU) ablation may be used in the management of atrial fibrillation for patients undergoing concomitant open heart surgery, e.g. mitral valve replacement or repair.^13,12
• Microwave ablation of the atria for patients with atrial fibrillation can be performed via a catheter introduced through a femoral vein or by surgical microwave ablation in patients undergoing concomitant open-heart surgery.¹⁴
• Thoracoscopic epicardial radiofrequency ablation has been shown to be effective, at least in the short term.¹⁵

• Warfarin substantially reduces risk of stroke by about 70%. The INR should be kept between 2-3 to optimize the therapeutic effect and minimise the risk of bleeding. A lower INR target of 1.5-3.0 has been shown to be safe and effective in the over 75 year age group.
• Even if normal rhythm cannot be restored, antiplatelet agents reduce the risk of stroke by about 22% and vitamin K antagonists, such as warfarin, reduce the risk by 64%.⁴
• Aspirin is less effective than oral anticoagulation in atrial fibrillation and, unless contraindicated, all elderly patients should receive warfarin. Aspirin is advocated for patients aged under 65 years and with no clinical or echocardiographic risk factors.
• Early results from The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III and V trials¹⁶ have suggested that ximelagatran may be an effective and safe alternative to warfarin in the future.

• Acute AF in haemodynamically unstable patients:
  • In patients with a life-threatening deterioration in haemodynamic stability following the onset of AF, emergency electrical cardioversion should be performed, irrespective of the duration of the AF.
• In patients with non-life-threatening haemodynamic instability following the onset of AF:
  • Electrical cardioversion should be performed.
  • Where there is a delay in organising electrical cardioversion, intravenous amiodarone should be given.
  • For those with known Wolff–Parkinson–White syndrome: Flecainide may be used as an alternative for attempting pharmacological cardioversion. Atrioventricular node-blocking agents (e.g. diltiazem, verapamil or digoxin) should not be used.
• In patients with known permanent AF where haemodynamic instability is caused mainly by a poorly controlled ventricular rate, a pharmacological rate-control strategy should be used.
• Where urgent pharmacological rate-control is indicated, intravenous treatment should be with beta-blockers or rate-limiting calcium antagonists; amiodarone should be used if beta-blockers or calcium antagonists are contraindicated or ineffective.

• Rhythm-control for paroxysmal AF:
  • More than half of patients with paroxysmal AF revert to sinus rhythm within a few days and so specific treatment of AF may not be required.
  • Medication to be used only as required:
    • Where patients have infrequent paroxysms and few symptoms, or where symptoms are induced by known precipitants (e.g. alcohol, caffeine), a ‘no drug treatment’ strategy or a ‘pill-in-the-pocket’ strategy should be considered.
    • A ‘pill-in-the-pocket’ strategy should be considered in those who have no history of left ventricular dysfunction, or valvular or ischaemic heart disease; and have a history of infrequent symptomatic episodes of paroxysmal AF; and have a systolic blood pressure greater than 100 mmHg and a resting heart rate above 70 bpm; and are able to understand how to, and when to take the medication.
  • In patients with symptomatic paroxysms (with or without structural heart disease, including coronary artery disease) a beta-blocker is first choice.
  • In patients with paroxysmal AF and no structural heart disease: If symptomatic suppression is not achieved with beta-blockers, either a Class Ic agent (e.g. flecainide or propafenone) or sotalol should be given. If suppression of symptoms is still not achieved, either amiodarone or referral for non-pharmacological intervention should be considered.
  • In patients with paroxysmal AF and coronary artery disease: If beta-blockers do not achieve symptomatic suppression, sotalol should be given. If suppression of symptoms is still not achieved, either amiodarone or referral for non-pharmacological intervention should be considered.
  • In patients with paroxysmal AF with poor left ventricular function: If beta-blockers do not adequately suppress paroxysms, either amiodarone or referral for non-pharmacological intervention should be considered.
• Antithrombotic therapy for paroxysmal AF: Decisions on the need for antithrombotic therapy in patients with paroxysmal AF should not be based on the frequency or duration of paroxysms (symptomatic or asymptomatic) but on appropriate risk stratification, as for persistent or permanent AF (see above).

• Irrespective of whether a rate-control or a rhythm-control strategy is adopted in patients with persistent AF, appropriate antithrombotic therapy should be used.
• A rhythm-control strategy should be the preferred initial option in the following patients with persistent AF:
  • Those who are symptomatic
  • Patients aged 65 years or younger
  • Those presenting for the first time with lone AF
  • Those with AF secondary to a treated/corrected precipitating factor
  • Those with congestive heart failure
• A rate-control strategy should be the preferred initial option in the following patients with persistent AF:
  • Over 65 years old
  • With coronary artery disease
  • With contraindications to antiarrhythmic drugs
  • Unsuitable for cardioversion
  • Without congestive heart failure
• Rhythm-control for persistent AF:
  • Electrical cardioversion.
  • An antiarrhythmic drug is not required to maintain sinus rhythm in patients with persistent AF in whom a precipitating factor has been corrected and cardioversion has been performed successfully, providing there are no risk factors for recurrence (e.g. a history of failed attempts at cardioversion, mitral valve disease, left ventricular dysfunction or an enlarged left atrium, prolonged AF (>12 months) or previous recurrences of AF).
  • In patients with persistent AF who require antiarrhythmic drugs to maintain sinus rhythm:
    • In presence of structural heart disease: A beta-blocker is first choice; amiodarone should be used if a beta-blocker is ineffective, contraindicated or not tolerated.
    • If no structural heart disease: A beta-blocker is first choice; a Class Ic agent or sotalol should be used if a standard beta-blocker is ineffective, contraindicated or not tolerated. If other drug classes are ineffective, contraindicated or not tolerated amiodarone should be used.
• Rate-control for permanent AF:
  • Beta-blockers or rate-limiting calcium antagonists are first choice. Digoxin should only be considered as monotherapy in predominantly sedentary patients.
  • If monotherapy is inadequate, beta-blockers or rate-limiting calcium antagonists should be given with digoxin to control the heart rate only during normal activities. To control the heart rate during both normal activities and exercise, rate-limiting calcium antagonists should be given with digoxin.

The NICE guidelines recommend further specialist intervention (e.g. for pulmonary vein isolation, pacemaker insertion, surgery, AV junction ablation or use of atrial defibrillators) for:²

• When pharmacological therapy has failed.
• Patients with lone AF.
• With ECG evidence of any underlying electrophysiological disorder, e.g. Wolff-Parkinson-White syndrome.

• In resistant cases, radiofrequency ablation of aberrant conduction pathways or radio-ablation of the AV node and permanent pacemaker may be considered.
• Other procedures include cryoablation, microwave ablation and high-intensity focused ultrasound.
• The Maze procedure is an option for patients with atrial fibrillation who are also undergoing mitral valve procedures. Its role as a primary therapy for atrial fibrillation is doubtful.

• Atrial fibrillation increases risk of stroke six-fold (much more in patients with rheumatic heart disease), and becomes increasingly important as a risk factor for stroke with increasing age. Paroxysmal as well as persistent atrial fibrillation increases risk of stroke.
• The risk of stroke is less in patients with no other structural heart disease ('lone AF').
• Atrial fibrillation can also precipitate acute heart failure and aggravate established heart failure.
• Chronic atrial tachyarrhythmia may lead to cardiomyopathy.
• Atrial fibrillation is associated with an approximate doubling of the risk of premature death.

• Atrial fibrillation is associated with reduced life expectancy in older patients.
• People with atrial fibrillation have double the mortality and a four to fivefold higher risk of stroke than those without fibrillation.⁴
• Prognosis depends on the patient's underlying medical condition.
• Any atrial arrhythmia can cause a tachycardia-induced cardiomyopathy.

• Smoking cessation; smoking is a risk factor for coronary heart disease as well as a precipitating factor for atrial fibrillation.
• Alcohol moderation or avoidance; acute alcoholic intoxication or alcohol withdrawal may precipitate paroxysmal atrial fibrillation.
• Diet; caffeine may induce paroxysmal atrial fibrillation in susceptible individuals.