ARRHYTHMIAS104

Atrial fibrillation and flutter — epidemiology andmechanisms

Atrial fibrillation

Atrial fibrillation is a supraventricular arrhythmia characterisedby rapid, chaotic depolarisation of the atria. The atrial rhythmis irregular, with rate from 300–500 per minute. Although theAV node limits the number of these impulses that reach theventricles, atrial fibrillation usually produces a rapid, irregularventricular rhythm (Fig. 1; Table 1). Since the AV nodedetermines heart rate, the ventricular rate tends to be slower inelderly patients in whom the AV node conducts less well.

Epidemiology

Atrial fibrillation is the most common arrhythmia seen ingeneral practice and hospital medicine. It is especiallycommon in the elderly, with a prevalence of 0.5% in theadult population, rising to 10% among individuals aged over75 years. It is associated with a 5–6-fold increase in theincidence of stroke. A 70-year-old with atrial fibrillation thushas an annual risk of stroke or transient cerebral ischaemicattack of 5%. Risk factors for atrial fibrillation consist mainlyof conditions that lead to increased atrial wall stress. Theseare summarised in Table 2.

Clinical manifestations

Atrial fibrillation can be paroxysmal, persistent or permanent.Paroxysmal atrial fibrillation is characterised by intermittent,self-terminating episodes of tachycardia. Sometimes thisprogresses to persistent atrial fibrillation, in which anintervention (such as direct current [DC] cardioversion, pp.106–107) may restore sinus rhythm, or permanent atrialfibrillation, which is resistant to such treatments.

Atrial fibrillation may not produce symptoms, especially ifthe associated heart rate response is not rapid. If symptomsoccur, their severity is determined by the underlying conditionof the heart, and patients’ heart rate at rest and during exercise.Patients may describe fatigue or reduced effort tolerance, ormore definite symptoms of palpitation, dyspnoea anddizziness. If the heart rate is rapid, cardiac failure or angina maydevelop in susceptible patients. It is rare for atrial fibrillation tocause syncope, unless the patient has severe left ventricularimpairment or valvular stenosis. In some cases, the first clinicalmanifestation of atrial fibrillation is stroke or systemicembolism. This is caused by the development of thrombus inthe left atrial appendage (Fig. 2), due to loss of atrial mechanicalfunction and stasis, followed by embolisation.

Mechanisms

Atrial fibrillation is the result of substrate and trigger. Thesubstrate usually consists of a disease that affects the atria,such as ischaemic heart disease (associated with atrialischaemia and infarction). The trigger often consists of arapidly discharging ectopic atrial focus. Although this focuscan arise anywhere in the atria, left atrial foci, occurring at or

within the pulmonary vein orifices, are commonly responsiblefor episodes of atrial fibrillation in patients with otherwiseapparently normal hearts (Fig. 3). Once initiated, thearrhythmia is maintained by re-entry (pp. 98–99). Macro re-entry occurs when a continuous loop of atrial depolarisation isset up around an anatomical or functional conduction barrier(e.g. vein orifice, zone of diseased atrial tissue). During atrialfibrillation, multiple re-entry circuits are established in theatria. These circuits tend to maintain themselves more readilyin diseased or enlarged atria. Once atrial fibrillation isestablished, the chance of spontaneous return to sinus rhythmdiminishes because of maladaptive changes that occur in atrialtissue. This includes shortening of the refractory period ofatrial myocytes, which encourages macro re-entry becausemyocytes are excitable for a greater proportion of each cardiaccycle. This process is known as electrical remodelling.

Atrial flutter

Atrial flutter is a related arrhythmia that shares the same riskfactors as atrial fibrillation (with the exception ofthyrotoxicosis). The mechanisms that underlie thesearrhythmias are different, resulting in distinct clinicalmanifestations, electrocardiographic characteristics andtreatment options.

Clinical manifestations

Atrial flutter can also present in paroxysms or as a persistentarrhythmia. If 2:1 AV block occurs, the presentation may bewith regular, rapid palpitation. (Rarely, 1:1 AV conduction canoccur in young patients, and this may cause an extremetachycardia, presyncope or syncope.) Otherwise the clinicalfeatures are similar to those of atrial fibrillation. Atrial stasis canoccur with atrial flutter (because of loss of atrial contraction)

V1Fig. 1 Rhythm strip of atrial fibrillation.

Fig. 2 Transoesophageal echocardiogram showing thrombus inthe left atrial appendage caused by stasis. In atrial fibrillation,atrial mechanical function is lost, predisposing to left atrial thrombus andembolic events.

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(pp. 116–117). The AV node limits theventricular response to atrial flutter.Often 2:1 or 4:1 AV block occurs,resulting in a regular ventricularrhythm of 150 or 75 beats per minute(Fig. 6). Variable AV block can alsooccur, resulting in an irregularventricular rhythm as with atrialfibrillation (Table 3).

105Atrial fibrillation and flutter — epidemiology and mechanisms

and thromboembolic complications dooccur, although the risk is not as high aswith atrial fibrillation.

Mechanisms

Atrial flutter is usually the result of asingle, large re-entry circuit within theright atrium (Figs 4 and 5). This circuit iscentred round the tricuspid valve ring(annulus), and the left atrium isactivated passively from this circuit. Inmost cases the atria depolarise at a rateof around 300 beats per minute.Importantly, the flutter circuit passesthrough a narrow strip of tissue (knownas the ‘flutter isthmus’) in between thetricuspid annulus and the inferior venacava. This strip of tissue can be targetedfor radiofrequency ablation, a potentiallycurative treatment for this arrhythmia

Atrial fibrillation andflutter — epidemiology

and mechanisms

■ Atrial fibrillation is caused by multiple,interlacing re-entry circuits involvingpredominantly the left atrium.

■ Risk factors include age, hypertension,mitral valve disease, cardiomyopathy andcoronary artery disease.

■ Atrial fibrillation affects around 10% ofpeople aged over 75 years.

■ Episodes of atrial fibrillation may betriggered by ectopic beats originating inthe pulmonary veins.

Fig. 5 Three-dimensional map of right atrial depolarisation obtained during electrophysiological study for atrial flutter. This is a map ofthe right atrium viewed through the tricuspid annulus (red ring). The depolarisation wave (denoted by concentric colours) passes between the tricuspid annulus(TV6) and the inferior vena cava (IVC).

Pulmonaryveins

Bundleof His

Sino-atrialnode

RV

LV

Fig. 3 Ectopic beats can arise from sleevesof conducting tissue within thepulmonary veins. These can trigger episodesof atrial fibrillation.

SVC

IVC

Eustachianridge

CS

1

2

3 6

TV

4

5

Fig. 4 Schematic of atrial flutter circuit. Themain structures in the right atrium are thetricuspid valve (TV), coronary sinus (CS), superiorvena cava (SVC) and inferior vena cava (IVC). Thecircuit itself runs around the tricuspid annulus.

F

F

F

F F F

Fig. 6 ECG leads showing atrial flutterwith 4:1 AV block. The flutter waves (F) occurat a rate of 300 per minute.

Table 1 Key ECG features of atrialfibrillation

■ No consistent organised atrial activity

■ Unsteady baseline (fibrillation waves)

■ Irregular ventricular rhythm (unless third-degree

AV block also present)

Table 2 Risk factors for atrial fibrillation

■ Advanced age

■ Valvular heart disease (especially mitral valve disease)

■ Hypertension

■ Ischaemic heart disease (per se and with heart failure)

■ Cardiomyopathies

■ Thyrotoxicosis

Table 3 Key ECG features of atrial flutter

■ Consistent organised atrial activity

■ Flutter waves prominent in inferior leads (II, III, aVF)

■ Regular or irregular ventricular rhythm may be seen

■ A regular, narrow complex tachycardia of 150 bpm

is likely to be atrial flutter with 2:1 AV block. Flutter

waves may be masked by the QRS complexes and

T waves, but may be unmasked by i.v. adenosine

(pp. 110–111)

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ARRHYTHMIAS106

Atrial fibrillation and flutter — management

Persistent atrial flutter/fibrillation

Two types of management strategy can be adopted — ratecontrol and rhythm control. With rate control, the atrialarrhythmia itself is not terminated and treatment is directedat controlling the ventricular response and preventingembolic complications. With rhythm control, treatment isdirected at restoring and maintaining sinus rhythm. Bothstrategies have advantages and disadvantages. The choice isgoverned by risk of thromboembolic complications, severityof symptoms and an assessment of whether the patient islikely to maintain sinus rhythm. Patients with long-standingatrial fibrillation (especially if due to mitral valve disease,hypertension or advanced LV dysfunction) are least likely tomaintain sinus rhythm after cardioversion. Recent evidence(the AFFIRM trial) suggests that aggressive attempts torestore sinus rhythm in asymptomatic patients may beharmful and increase the risk of stroke.

Rhythm control strategy

The rhythm control strategy (Table 1) uses cardioversion torestore sinus rhythm. Cardioversion is most often achievedusing a synchronised direct current (DC) shock applied tothe chest with paddles placed over the apex and base of theheart. This procedure is performed under generalanaesthesia. Cardioversion can also be achieved usingantiarrhythmic drugs such as flecainide or amiodarone; thispharmacological cardioversion is normally used to restoresinus rhythm in patients with acute atrial fibrillation (of lessthan 48 hours duration). For patients with established atrialfibrillation, four weeks of prior anticoagulation (target INR2.0 to 3.5) is mandatory. Here, cardioversion is dangerouswithout prior anticoagulation. Restoration of atrialmechanical function can cause ejection of clot from the leftatrial appendage in the days following the procedure.Warfarin should be continued for at least 12 weeks aftercardioversion, and only stopped if sinus rhythm is stillmaintained and likelihood of recurrence considered low.

DC cardioversion Long-term success rates are disappointing with cardioversion(< 50% of patients maintain sinus rhythm at six months)(Table 2). Concomitant use of antiarrhythmic drugs increasesthe proportion of patients that maintain sinus rhythm.Amiodarone, sotalol, propafenone and flecainide are effectivebut can be proarrhythmic and have other significant sideeffects (Table 3). Therefore, unless the patient has a history ofintermittent atrial fibrillation progressing to chronic atrialfibrillation or has had a previous cardioversion withrecurrence, antiarrhythmic drugs are not normally given.

Rate control strategy

Recent trials suggest that the rate control strategy (Table 4) isat least as safe as rhythm control, and is especiallyappropriate in asymptomatic patients — it avoids the hazardsof cardioversion and antiarrhythmic drugs.

Drugs for rate controlAV node blocking drugs are used to control heart rate. Ahierarchy of drugs is given in Table 5. β-blockers and

digoxin are preferable in patients with significantventricular impairment. The target is a resting heart rate of50–80 bpm.

In atrial flutter, rate control is difficult because the AV nodeblocking response is not linear, and is usually a wholefraction of an atrial rate of around 300 min–1. Thus, atherapeutic dose of digoxin may not reduce heart rate from150 bpm (2:1 AV block), but an additional agent may cause itto fall abruptly to 75 bpm (4:1 block) or lower.

Table 1 Rhythm control strategyAdvantages Disadvantages

■ Restoration of atrial contraction ■ General anaesthetic risk (not a major concern

— ↑ cardiac output with exercise for most patients)

— appropriate rate response to ■ Drugs used to maintain sinus rhythm generally

exercise have more proarrhythmic potential than do the

AV node blocking drugs used for rate control.

■ Recent evidence suggests embolic risk may be

increased

Table 2 DC cardioversion protocol

■ Ensure patient has had at least three weeks of effective (INR>2) anticoagulation

■ Check serum K+ (success greater if > 4.0 mmol. L1-1)

■ Patient fasting > 6 hours

■ i.v. access

■ General anaesthesia with short-acting induction agent

■ Cardiovert using following protocol (start at 200 J for atrial fibrillation):

— 100 J synchronised shock (or 50 J biphasic) if fails →

— 200 J synchronised shock (or 100 J biphasic) if fails →

— 360 J synchronised shock (or 150 J biphasic) if fails →

— 360 J anteroposterior shock

— [lower shock energies used (up to 150 J) with biphasic shock defibrillator]

■ Continue warfarin for at least 3 months if cardioversion successful

■ If cardioversion unsuccessful, consider repeating at later date after pre-treatment with

antiarrhythmic agent (e.g. amiodarone)

Table 3 Drugs to maintain sinus rhythmClass Ic drugs (sodium channel blockers)

These agents should be avoided in patients with IHD or heart failure. In patients with

structurally normal hearts, the incidence of proarrhythmia is around 1%

■ flecainide 50–100 mg BD

■ propafenone 150 mg BD to 300 mg TID

Class II drugs (β-blockers)

These have little proarrhythmic effect, and are a sensible first-line agent, especially when

ischaemia or heart failure is implicated as a cause

■ atenolol 25–100 mg D

■ metoprolol 25–100 mg BD

Class III drugs (potassium channel blockers)

Sotalol has combined β-blocking and class III activity. It causes proarrhythmia by causing

abnormal ventricular repolarisation (seen as QT interval prolongation). This can lead to

polymorphic ventricular tachycardia/sudden death. Proarrhythmia with sotalol is more

common in women and in patients with LVH. Amiodarone is the safest agent in patients with

significant LV compromise. It has many side effects (see pp 104–105, Fig. 4) and should be

avoided in young patients unless no effective alternative is found

■ sotalol 60–120mg BD

■ amiodarone 100–400 mg D (usual dose 200 mg D)

For all of the above agents, except β-blockers, ambulatory monitoring within the first five

days of treatment is sensible to identify proarrhythmia

Table 4 Rate control strategyAdvantages Disadvantages

■ More appropriate for patients with valve ■ Loss of atrial contribution to

disease or previous failed cardioversions cardiac output

■ Less proarrhythmic potential from rate ■ Risk of embolic complications

controlling drugs

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107Atrial fibrillation and flutter — management

Anticoagulation

Most patients with chronic atrial flutter/fibrillation requirelong-term anticoagulation with warfarin. Exceptions arepatients who, from anticoagulation trials, are considered lowrisk. In these cases, low-dose aspirin 75–300 mg daily issufficient prophylaxis. The European Society of Cardiologyhas produced anticoagulation guidelines which aresummarised in Table 6.

Intermittent atrial flutter/fibrillation

Intermittent atrial flutter/fibrillation may be a prelude tochronic atrial fibrillation, but can exist as a separate entity.The need for antiarrhythmic drugs is dictated by the severityof symptoms. Anticoagulation may be needed if prolonged(> 24 hours) episodes occur. Ambulatory ECG monitoringhelps guide treatment. Identification and treatment ofpotential precipitants (e.g. hypertension, alcohol, valvedisease) should be done before committing to long-termantiarrhythmic treatment.

Non-pharmacological treatments

Radiofrequency ablationRadiofrequency ablation can be used to treat intermittent orpersistent atrial flutter; the isthmus zone described on pages

104–105 is targeted. Current success rates are 80–90%.Ablation can also be used to treat atrial fibrillation, bytargeting triggering foci in the pulmonary veins (Figs 1 and2). This evolving treatment has a success rate of around 65%in patients with otherwise normal hearts. ‘Dynamic overdrive’pacemakers have recently been developed to suppress ratechanges and ectopic activity that may trigger atrial fibrillation(Fig. 3). The pace and ablate strategy is used as a last resort forsymptomatic patients in whom drug treatment is ineffectiveor poorly tolerated. Rate control is achieved by ablation of theAV node and implantation of a permanent pacemaker.

Atrial fibrillation and flutter — management

■ The rate control strategy is directed at limiting the ventricular responseto atrial fibrillation by using AV node blocking drugs such as digoxin,ß-adrenoceptor antagonists and verapamil.

■ The rhythm control strategy uses cardioversion and antiarrhythmicdrugs to restore and maintain sinus rhythm.

■ Anticoagulation with warfarin should be considered for patients withatrial fibrillation and risk factors for stroke.

■ Pacemaker implantation and AV nodal ablation can be used to controlheart rate in patients for whom drugs fail or are not tolerated.

Fig. 1 Computer-generated map of the left atrium in a patientwith atrial fibrillation due to pulmonary vein ectopy. The red dotsaround the right upper pulmonary vein (RUPV) denote ablation lesionsdelivered during the procedure. (RLPV, right lower pulmonary vein.)

Table 6 ESC guidelines for anticoagulation in atrial fibrillation

■ Age > 60 years with diabetes or CAD

■ Age > 75 years (esp. women)

■ Current or prior hypertension

■ Heart failure

■ History of TIA, stroke or other embolic event*

■ Rheumatic heart disease or prosthetic valve*

Warfarinise, INR range 2.0–3.0 except highest risk cases (*) where target range is 2.5–3.5.

Table 5 Oral drugs for rate control in atrial fibrillationFirst line

Digoxin 250 µg D (after leading with 600–1200 mg for one week) OR

Verapamil 240 to 480 mg D OR

Diltiazem 200 to 500 mg D OR

β-blocker (e.g. atenolol 50 to 100 mg D)

If digoxin ineffective, ensure blood level therapeutic before adding a second agent

Second line

Combination of digoxin and either verapamil or β-blocker

Third line

Amiodarone 100 to 400 mg daily (after loading ⊗)

I

III

aVF

V1

RA 1,2

RA 3,4

RA 5,6

RA 7,8

RA 9,10

RA 11,12

RA 13,14

Fig. 2 Surface (ECG (top four traces) and intracardiac electrogramsfrom right atrium, (RA) during successful ablation of atrial flutter.Rapid, regular atrial depolarisation is seen to proceed around the right atriumuntil sinus rhythm is restored by blocking the flutter circuit (see pp. 116–117).

Fig. 3 AF suppression pacemaker. This device paces the atria slightlyfaster than the sinus rate, preventing bradycardia and atrial ectopy thatotherwise trigger atrial fibrillation.

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