Atrial Fibrillation: Diagnosis, Rate Control and Stroke Prevention

Introduction

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, affecting around 2% of the UK population and over 10% of those aged 80 and above.¹ Its prevalence is rising as the population ages and as survival from ischaemic and valvular heart disease improves.

In AF, organised atrial contraction is replaced by chaotic electrical activity at 300-600 impulses per minute. The AV node conducts only a fraction of these, and does so unpredictably, producing the characteristic irregularly irregular ventricular response.

Two consequences follow, and between them they define the management:

1. Loss of atrial contraction removes the atrial contribution to ventricular filling, which accounts for up to 20-30% of cardiac output. Combined with a fast and irregular ventricular rate, this causes breathlessness, fatigue and, if sustained, heart failure.
2. Stasis of blood in the fibrillating left atrium, particularly in the left atrial appendage, allows thrombus to form. Embolisation of that thrombus causes ischaemic stroke, and it is this risk - rather than the arrhythmia itself - that drives most of the morbidity and mortality of AF.

AF-related strokes are on average larger, more disabling and more often fatal than strokes of other aetiology, because the embolus is a formed thrombus that occludes a proximal cerebral vessel. Recognising AF and anticoagulating appropriately is therefore among the highest-value interventions in general medicine.

Classification

AF is classified by how it behaves over time. This matters because it influences whether rhythm control is likely to succeed.

Two further terms appear frequently and cause confusion:

• Valvular AF - in current usage this means AF in the presence of moderate to severe mitral stenosis or a mechanical prosthetic heart valve. The distinction matters because these patients require warfarin, not a DOAC.
• Lone AF - an older term for AF in a young patient with no structural heart disease or identifiable cause. It is falling out of use, since better investigation usually reveals a cause.

Aetiology

AF arises from a combination of a trigger - most often ectopic firing from muscular sleeves around the pulmonary vein ostia - and a susceptible atrial substrate, usually a dilated and fibrosed left atrium. The importance of the pulmonary veins is the rationale for pulmonary vein isolation in catheter ablation.

Cardiac causes

• Hypertension - the commonest cause in the UK, through left atrial pressure overload and dilatation
• Ischaemic heart disease - including AF complicating acute myocardial infarction
• Heart failure - a bidirectional relationship, each precipitating and worsening the other
• Valvular heart disease - particularly mitral stenosis and mitral regurgitation, both of which dilate the left atrium
• Cardiomyopathy - dilated, hypertrophic and infiltrative
• Pericarditis and myocarditis
• Congenital heart disease - especially atrial septal defect
• Post-cardiac surgery - occurring in up to a third of patients, typically on days 2-4
• Sick sinus syndrome - the tachy-brady syndrome, alternating AF with sinus pauses

Non-cardiac causes

• Thyrotoxicosis - always check thyroid function in new AF; AF may be the only manifestation in older patients (apathetic thyrotoxicosis)
• Alcohol - both binge drinking (holiday heart syndrome) and chronic excess
• Sepsis and any acute illness - AF here is often a marker of systemic upset rather than a primary cardiac problem
• Pulmonary embolism - AF with breathlessness and hypoxia should prompt consideration of PE
• Pneumonia and COPD
• Obstructive sleep apnoea - increasingly recognised, and treating it reduces AF recurrence
• Obesity - a strong, dose-dependent and modifiable risk factor
• Electrolyte disturbance - hypokalaemia and hypomagnesaemia
• Caffeine, stimulants and cocaine
• Endurance exercise - paradoxically increases AF risk at extremes of training volume

Clinical features

AF is asymptomatic in around a third of patients and is frequently found incidentally on a routine examination, a pre-operative ECG, or a blood pressure machine reporting an irregular rhythm.

Symptoms

• Palpitations - typically described as irregular, fluttering or racing
• Breathlessness - on exertion, or at rest if the rate is very fast
• Fatigue and reduced exercise tolerance - often the dominant symptom in older patients
• Chest pain - from the increased myocardial oxygen demand of a rapid rate
• Dizziness, presyncope or syncope - syncope raises the possibility of tachy-brady syndrome with a long pause on termination
• Symptoms of a complication - stroke or TIA as the first presentation, or decompensated heart failure

Examination

• Irregularly irregular pulse with variable pulse volume - the cardinal sign. Take the pulse for a full minute.
• Apical-radial pulse deficit - the apical rate exceeds the radial rate because some beats follow too short a diastolic filling period to generate a palpable peripheral pulse. This is characteristic of AF and useful in an OSCE.
• Absent a waves in the JVP - there is no organised atrial contraction to produce one
• Variable intensity of the first heart sound - a consequence of variable diastolic filling time
• Signs of a cause - a mid-diastolic murmur of mitral stenosis, goitre and tremor of thyrotoxicosis, signs of heart failure, or a large body habitus
• Signs of a complication - focal neurological deficit, or pulmonary oedema

Investigations

ECG

A 12-lead ECG is required to confirm the diagnosis in every patient. Manual pulse palpation is the screening test; the ECG is the diagnostic one.¹

• Absent P waves, replaced by a chaotic fibrillatory baseline (f waves), best seen in V1
• Irregularly irregular R-R intervals
• Narrow QRS complexes, unless there is pre-existing or rate-related bundle branch block
• Look also for ischaemic changes, left ventricular hypertrophy, pre-excitation and evidence of prior infarction

If paroxysmal AF is suspected and the resting ECG is normal, arrange ambulatory monitoring: a 24-hour Holter for daily symptoms, and a longer patch monitor or event recorder for less frequent episodes.

Blood tests

• Thyroid function tests - mandatory in all new AF
• U&Es - potassium, magnesium and renal function, the last of which determines DOAC dosing
• FBC - anaemia as a precipitant, and baseline haemoglobin before anticoagulation
• LFTs - baseline before anticoagulation; severe liver disease with coagulopathy contraindicates DOACs
• Coagulation screen
• Glucose and HbA1c, and a lipid profile as part of cardiovascular risk assessment
• Troponin if ischaemia is suspected, and BNP or NT-proBNP if heart failure is suspected

Imaging

• Transthoracic echocardiogram - to assess left atrial size, left ventricular function, and valve disease, particularly mitral stenosis. Indicated where a baseline echocardiogram will influence management, where rhythm control is being considered, or where structural disease is suspected.
• Transoesophageal echocardiogram - the only reliable way to exclude left atrial appendage thrombus, used to permit early cardioversion in AF of over 48 hours or unknown duration
• Chest X-ray - if pneumonia, heart failure or another respiratory precipitant is suspected

Management: the three questions

Management of AF resolves into three separate decisions, and it is worth answering them in this order because the first two can be urgent.

1. Is the patient haemodynamically unstable? If so, immediate synchronised DC cardioversion.
2. Does the patient need anticoagulation? This is the decision that prevents the most harm, and it is independent of whether rate or rhythm control is chosen.
3. Rate control or rhythm control? For most patients, rate control.

The unstable patient

Anticoagulation and stroke prevention

This is the single most important decision in AF and the one most heavily examined. Assess every patient with AF - paroxysmal, persistent or permanent - and reassess at every review.

CHA2DS2-VASc

Female sex scores a point but is a risk modifier rather than a risk factor: a woman under 65 with no other risk factors and a score of 1 does not need anticoagulation.

Assessing bleeding risk

NICE recommends the ORBIT score to assess bleeding risk, having previously used HAS-BLED.¹ It uses older age, reduced haemoglobin or a history of anaemia, bleeding history, renal impairment and antiplatelet treatment.

Choice of anticoagulant

• A DOAC is first line - apixaban, rivaroxaban, edoxaban or dabigatran. They need no routine monitoring, have fewer food and drug interactions than warfarin, and cause less intracranial haemorrhage.¹
• Warfarin is used where a DOAC is contraindicated: moderate to severe mitral stenosis, a mechanical prosthetic heart valve, antiphospholipid syndrome, or severe renal impairment. Target INR 2-3, with time in therapeutic range monitored.
• Dose reduction is required in renal impairment, low body weight, older age and with certain interacting drugs - check the specific criteria for each DOAC.
• Left atrial appendage occlusion is an option where anticoagulation is genuinely contraindicated, for example after recurrent life-threatening bleeding.
• Aspirin has no role in stroke prevention in AF. It provides minimal protection with a bleeding risk comparable to anticoagulation, and should not be prescribed for this indication.

Rate control

Rate control is the default strategy for most patients, and large trials have shown no mortality advantage to rhythm control in unselected populations. The aim is a resting ventricular rate below 110 beats per minute initially, tightened to below 80 if symptoms persist.¹

If drug therapy fails and symptoms are disabling, AV node ablation with permanent pacemaker implantation provides guaranteed rate control at the cost of pacemaker dependence. The AF continues, so anticoagulation must continue too.

Rhythm control

Rhythm control aims to restore and maintain sinus rhythm. NICE recommends it in preference to rate control where:¹

• AF has a reversible cause that has been treated
• AF is new onset (under 48 hours)
• AF is causing heart failure
• Symptoms persist despite adequate rate control, or rhythm control is judged more suitable on clinical grounds
• The patient is young, or this is a first symptomatic episode

The 48-hour rule

Cardioversion

• Electrical cardioversion - synchronised DC shock under sedation or general anaesthesia. More effective than pharmacological cardioversion, particularly in longer-standing AF.
• Pharmacological cardioversion - flecainide in a structurally normal heart, or amiodarone where there is structural or ischaemic heart disease. Flecainide is contraindicated in ischaemic heart disease and left ventricular dysfunction.
• Pill in the pocket - selected patients with infrequent, symptomatic paroxysms, a structurally normal heart and no history of left ventricular dysfunction may self-administer flecainide at the onset of an episode

Maintaining sinus rhythm

• Beta-blockers - first line for long-term rhythm control
• Flecainide or propafenone - effective in structurally normal hearts. Give with an AV nodal blocking drug, because a class Ic agent can organise AF into a slow atrial flutter that conducts 1:1 to the ventricles at a dangerous rate.
• Sotalol - a beta-blocker with class III activity; monitor the QT interval
• Amiodarone - the most effective agent and the one usable in structural heart disease, but limited by long-term toxicity
• Dronedarone - an alternative, contraindicated in heart failure and permanent AF

Catheter ablation

Pulmonary vein isolation electrically disconnects the pulmonary veins from the left atrium. It is offered to patients with symptomatic paroxysmal or persistent AF in whom drug treatment has failed or is not tolerated, and is increasingly used earlier, particularly in younger patients and in AF with heart failure, where it improves symptoms and ventricular function.

Success rates are around 70-80% for paroxysmal AF, though repeat procedures are often needed. Complications include cardiac tamponade, stroke, phrenic nerve palsy, pulmonary vein stenosis and, rarely, atrio-oesophageal fistula. Anticoagulation is determined by CHA2DS2-VASc and continues after a successful ablation - the procedure treats symptoms, not stroke risk.

Lifestyle measures

Often overlooked but genuinely effective: weight loss in obesity, alcohol reduction, treating obstructive sleep apnoea, blood pressure control, and regular moderate exercise. Structured weight loss and alcohol abstinence both reduce AF burden and recurrence after ablation in randomised trials.

Complications

• Ischaemic stroke and systemic embolism - the dominant complication. Around one in five ischaemic strokes is attributable to AF.
• Heart failure - through loss of atrial contraction and rate-related decompensation
• Tachycardia-induced cardiomyopathy - a persistently uncontrolled rate causes a dilated cardiomyopathy that is substantially reversible once rate is controlled
• Myocardial ischaemia - increased demand and reduced diastolic coronary filling
• Bleeding - from anticoagulation, principally gastrointestinal and intracranial
• Reduced quality of life - symptoms, hospital admissions, and anxiety
• Dementia - AF is independently associated with cognitive decline, likely through silent cerebral infarction

Red flags

Prognosis

AF is associated with approximately a doubling of all-cause mortality and a fivefold increase in ischaemic stroke risk. It also increases the risk of heart failure, dementia and hospitalisation, and reduces quality of life independently of these.

Anticoagulation transforms this picture. Warfarin reduces stroke risk by around two thirds and DOACs are at least as effective with less intracranial bleeding, making anticoagulation one of the most effective preventive interventions available in medicine. The great majority of AF-related strokes occur in patients who were eligible for anticoagulation but not receiving it, or receiving it subtherapeutically.

Prognosis otherwise depends on the underlying cardiac substrate. AF secondary to a reversible cause such as thyrotoxicosis, sepsis or alcohol may not recur once the cause is treated. AF in the context of heart failure, significant valve disease or a markedly dilated left atrium tends to become persistent and is a marker of a poorer outlook, though the AF is often as much a consequence of the underlying disease as a driver of it.