Atrial Fibrillation

Definition/diagnostic criteria Atrial fibrillation (AF) is a supraventricular tachyarrhythmia in which uncoordinated atrial electrical activation causes ineffective atrial contraction.

Diagnosis requires a standard 12-lead ECG or a single-lead ECG tracing showing:

• absence of distinct repeating P waves;
• irregular atrial activations (‘chaotic baseline’); and
• irregularly irregular R-R intervals when atrioventricular conduction is not impaired.

The minimum duration for the diagnosis of clinical AF is at least 30 secs of a single-lead ECG or entire 12-lead ECG.

Put simply, in sinus rhythm, every P wave should be followed by a QRS complex, and every QRS complex should be preceded by a P wave. Another simple rule of thumb is that if an ECG is fast and irregular, it’s most likely to be AF. However, beware the potential pitfalls:

• Frequent supraventricular ectopics cause irregularity which can create a superficial impression of AF due to R-R irregularity.
• An automated ECG diagnosis of AF (whether 12-lead or single-lead) requires visual review of the trace and confirmation by a cardiology specialist. Occasionally, automated 12-lead ECGs reports not only miss AF, but also inappropriately misdiagnose sinus rhythm as AF.
• On a 12-lead ECG, most clinicians assess the rhythm using the rhythm strip (conventionally lead II). Sometimes the underlying rhythm will not be clear in lead II so don’t forget that lead V1 is an excellent place to spot P waves – if there are clear P waves in lead V1 predictably followed by QRS complexes, then it is not AF.

Implantable cardiac devices (such as permanent pacemakers and defibrillators) offering continuous heart rhythm recording have led to recognition of atrial high-rate episodes (AHRE) which when confirmed with a surface ECG are described as sub-clinical AF. These entities are the subject of several ongoing RCTs expected to inform their management. Until these trials provide data on optimal management, GPs are not expected to provide advice on this area. While GPs may see mention of such episodes in clinical reports and be concerned that such episodes represent a ‘ticking timebomb’ for stroke or other complications, some comfort can be drawn from the fact that thromboembolic risk is reduced when the AF burden is very low.

Epidemiology Worldwide, AF is the most common sustained cardiac arrhythmia in adults, currently estimated to affect 2-4% adults (and around 10% of over 80-year-olds), with a 2.3-fold rise expected due to increasing longevity and intensified efforts to identify cases. Risk of AF increases dramatically with age, meaning a 55-year-old of European descent has about a one in three risk of developing AF. Other non-modifiable risk factors include male sex and Caucasian ethnicity. Commonly encountered reversible risk factors include hypertension, obesity, obstructive sleep apnoea and excess alcohol. Thyrotoxicosis can also trigger AF, although the above hyper-prevalent co-morbidities are usually more relevant in day-to-day practice. There is a powerful reciprocal relationship between AF and heart failure, the one increasing the likelihood and impact of the other.  Lifetime risk of AF increases with increasing risk factor burden.

Diagnosis

Clinical features Approximately half of patients with AF are asymptomatic. Registry data from 10,000 patients reported that in the 62% of patients who were symptomatic, one or more of the following were present:

• Palpitations (32%)
• Exertional dyspnoea (27%)
• Fatigue (26%)
• Dizziness (20%)
• Reduced exercise tolerance (10%)
• Dyspnoea at rest (10%)
• Chest tightness (9%)
• Syncope (4%)

Reduced mentation or polyuria are less common presentations.

In asymptomatic patients AF can be an incidental finding on an ECG or echocardiogram performed for other reasons such as preoperative assessment. Unfortunately, the diagnosis may be made when the patient presents with a complication, usually stroke, TIA or heart failure.

The different ways of characterising AF range from symptomatic versus asymptomatic, contextual (eg, post-operative) to classification based on duration.  The temporal pattern of AF influences ease of diagnosis and the likelihood of success of rhythm control strategies, but has little effect on decision making around rate control and stroke prevention. Paroxysmal atrial fibrillation (PAF) is particularly likely to cause intense, poorly tolerated symptoms, especially in younger patients.

Reported annual rates of transition from PAF to persistent AF range from 1-15% and increase to 36% in studies with ≥10 years follow up. Risk factors for progression include age, hypertension, obesity, CKD, chronic pulmonary diseases, diabetes mellitus, previous stroke and left atrial size. It should be emphasised that transition can by delayed or prevented by lifestyle changes that impact on the underlying substrate.

Investigations – for diagnosis In paroxysmal AF, the diagnostic strategy is determined by frequency of symptomatic episodes. NICE advise 24-hour Holter monitoring when symptomatic episodes come less than 24 hours apart or if asymptomatic episodes are suspected to occur with this frequency. For symptomatic episodes occurring less frequently, an event monitor or prolonged ambulatory monitoring was traditionally offered.

Due to the sometimes limited diagnostic utility of conventional ambulatory monitoring, cardiologists and some GPs are increasingly taking advantage of commercially available devices that patients own or are prepared to purchase. NICE approved KardiaMobile (incorporated in advanced Apple Watch models) are increasingly deployed and some GPs operate a loan scheme.

In persistent AF, the resting 12-lead ECG should be diagnostic although it can be missed (see pitfalls of ECG diagnosis above). Once present for over a year, described as longstanding persistent AF, this implies a lower success rate for rhythm control strategies as with extended duration comes atrial enlargement which is in turn is associated with lower cardioversion success rates and higher recurrence rates. When a protracted duration of AF combines with presence of evident risk factors for AF (such as unchanging obesity and significant left atrial enlargement) clinician and patient may agree not to attempt rhythm control at which point the condition is termed ‘permanent AF’.

In over 65s, opportunistic pulse palpation and the finding of an irregular pulse has an important role in raising the possibility of AF, as underlined by the reported sensitivity of 95-100%, although irregularity may not be apparent when ventricular rates are very high or very low. Specificity is respectable at 71-81%. Fluctuating stroke volume affects the performance of oximeters and automated BP manometers.

Commercially available self-monitoring technologies including ‘wearables’ are a growth area that GPs need to grapple with. For confirmation an equivalent to a single-lead ECG is needed, as provided by a dedicated connectable device like the NICE-approved KardiaMobile and by more advanced models of smartwatch or other wearables.

 Investigations – to identify causes, comorbidities and adequacy of control  Routine blood tests should include full blood count, renal, thyroid and liver function and measures to identify diabetes mellitus if not undertaken recently. Most authorities agree that an echocardiogram is an essential element in all new cases of AF to identify predisposing causes, assess LV function, evaluate concomitant valvular disease and help with stroke risk stratification.

In some instances of PAF, usually outside of the scope of GP management, ambulatory heart rhythm management will be carried out to assess AF burden. In cases where the indication for anticoagulation is marginal (eg, CHA₂DS₂VASc score of 1 in a man, or 2 in a woman) then demonstration of a high AF burden could tip the balance, as a greater burden of AF when not anticoagulated is associated with a higher risk of ischemic stroke and other arterial thromboembolism.

Another indication for ambulatory heart rhythm monitoring would be to test the adequacy of rate control in cases of previous rate-related cardiomyopathy or in patients with suboptimal symptom control not explained by sporadic resting ECGs.

 Treatment Treatment is broadly three-fold:

• Decisions around rate or rhythm control.
• Stroke risk assessment and reduction.
• Lifestyle interventions to reduce co-morbidities that in turn affect the AF trajectory.

Rate or rhythm control? The decision to choose rate or rhythm control hinges around the severity of symptomatology due to AF, the likelihood of relapse after cardioversion and patient choice.

In general GPs are faced with subacute presentations of AF in whom the first priority is often rate control. Rate control aims for a resting ventricular rate of <110bpm, so-called lenient rate control, which is prognostically equivalent to a stricter target of <80bpm. However stricter control is sought if symptoms persist with lenient rate control. Either beta blockers (except sotalol) or rate-limiting calcium channel blockers (RLCCBs; diltiazem or verapamil) can be used as first-line therapy unless there are contraindications. RLCCBs should be avoided in cases of LV dysfunction (unless LVSD is mild, ie, ejection fraction 50-55%, as in these cases the benefit of rhythm control can outweigh the disadvantage of negative inotropy).

Digoxin is added in if needed. Digoxin does not restrict ventricular rate during exercise (its major limitation in younger and active patients). Digoxin monotherapy can be used for initial rate control in people with non-paroxysmal AF if the person does little or no exercise or if other rate-limiting therapies are ruled out by comorbidities or the person’s preferences.

In patients presenting with AF and acute decompensated heart failure, GPs should avoid diltiazem or verapamil and seek specialist input regarding initial beta-blocker use due to all these agents’ negative inotropy.

While GPs are mainly concerned with initial rate control and anticoagulation, some familiarity with indications for rhythm control will guide referral and enhance GP confidence in overall management.  Haemodynamic compromise due to AF is an indication for admission for urgent cardioversion, usually direct current cardioversion (DCCV), but sometimes by use of anti-arrhythmic drugs (AADs) in specialists’ hands. Non-urgent referral for rhythm control is indicated for people whose AF has a reversible cause such as an acute intercurrent illness, surgery or an alcohol binge. The aim is to prevent the trajectory wherein ‘AF begets AF’. This aphorism describes how AF causes progressive atrial enlargement and electrical remodelling which in turn encourages recurrence or persistence of AF.

Rhythm control should also be considered if rate control does not restore a patient’s well-being.

Rhythm control may not be feasible if AF has been persistent for more than a year or if comorbidities, particularly obesity, OSA or alcohol misuse make AF recurrence inevitable. However, even in these situations, chemical cardioversion and continuation of an AAD can maintain sinus rhythm for some time, even years.

The initiation of AADs is usually done in secondary care but continued prescription and monitoring for adverse events falls to GPs, calling for some understanding of the three AADs most often used which are flecainide, sotalol and amiodarone.

Flecainide is often used as a pill-in-pocket measure for PAF. It is contraindicated in ischaemic heart disease, structural heart disease or LV dysfunction. Increasingly cardiologists insist on co-prescription of a beta blocker due to the potential for flecainide to cause atrial flutter with 1:1 conduction that can lead to dangerously high ventricular rates.

Sotalol may be advised by secondary care where rhythm control is intended, provided conventional beta-blockade has been well tolerated. The initiation and up titration of sotalol is usually specialist led but primary care may be involved at various points depending on locally agreed shared care guidelines.

Amiodarone has a considerable side effect profile, one in five patients suffering significant adverse effects. Due to the safety concerns NHS England (NHSE) and NHS Clinical Commissioners (NHSCC) guidance advises that prescribers should not initiate amiodarone in primary care for new patients. Therefore it must only be initiated by a specialist and used as a short-term measure where other agents have failed or are contraindicated, or in patients with limited life expectancy in whom the drug offers important symptom relief. All patients should have six-monthly monitoring of TFTs and LFTs and an annual review which includes an ECG. If a patient is receiving amiodarone to maintain sinus rhythm but is found to have reverted to AF, the GP should access cardiological advice as the amiodarone will likely be discontinued unless it is being prescribed for other tachyarrhythmias.

Stroke risk assessment and reduction AF is associated with a five-fold increased risk of stroke and thromboembolic complications. GPs may be aware of controversy stemming from the lack of temporal relationship between onset of AF and stroke. Continuous ECG monitoring provided by implantable cardiac devices has revealed that a thromboembolic stroke may precede the first ever onset of AF, casting doubt on the concept of intra-atrial clot forming during episodes of AF and subsequently embolising. Instead, the current view is that AF is both a cause and a marker of atrial cardiomyopathy, and that changes in atrial wall structure and function predisposing to thromboembolism can precede the development of AF.

Stroke risk reduction has been significantly eased by the availability of direct acting oral anticoagulants (DOACs) which when compared with warfarin offer the same or possibly superior risk reduction whilst being associated with a lower risk of intra-cranial haemorrhage, the most feared potential adverse effect.

The decision to anticoagulate should incorporate an assessment of bleeding risk (for example using ORBIT or HAS-BLED scores), with elevated bleeding risk not being a reason to withhold DOACs but an indicator of the need for bleeding risk mitigation. This might include prescription of a PPI, additional efforts to reduce falls, or reductions in polypharmacy.

Lifestyle management Identification and management of risk factors and concomitant diseases is recommended by the European Society of Cardiology (ESC) as an integral part of treatment in AF patients.

Elevated body mass index is the strongest modifiable risk factor for AF. Mendelian randomisation studies demonstrate this link to be causal and 80% of AF patients are overweight or obese. BMI >30 at the time of ablation carries a significantly higher risk of AF recurrence than patients of normal or overweight BMI. Once BMI exceeds 35, the risk of recurrence becomes so high that many centres now insist on weight loss before an ablation is attempted. Weight loss also reduces the progression of PAF to persistent AF.

Hypertension is an independent risk factor for AF recurrence and BP control should be optimised. Where medications are used, dual antihypertensive therapy is advised which reduces adverse cardiovascular outcomes.

Lipids as an isolated risk factor for CVD should be optimised in order to reduce stroke risk alongside AF management.

It is well recognised that some people are more susceptible to the effects of alcohol on the heart as well as the liver. Binge drinking can precipitate AF (‘holiday heart’) as can sustained high intake.

In general exercise is beneficial apart from extreme endurance exercise which can be a precipitant for AF.

Prognosis AF is independently associated with a two-fold increase in mortality in women and 1.5-fold increase in men. Overall, it carries with it a 3.5-fold increase in mortality to which the frequently accompanying comorbidities contribute. The excess mortality relates to increased rates of stroke and heart failure and the impact of comorbidities, all three of which therefore require active management.

Morbidity is increased as a result of stroke (AF contributes to 20-30% of all ischaemic strokes and 10% of cryptogenic strokes); heart failure (20-30% incidence in AF patients); cognitive decline and dementia irrespective of strokes (HR=1.4-1.6); depression (affecting 16-20%, related to symptom impact and medication effects); impaired quality of life (over 60%); and increased hospitalisations (10-40% annual rate).

When counselling patients it is vital to emphasise the available mitigating factors and the potential for lifestyle changes to reduce the burden of AF (time spent in AF), its driving factors (eg, obesity, hypertension) and its physical and psychological impact.

Although screening for AF fulfils many of the criteria for national disease screening there is currently a need for trial evidence to confirm that the presumed clinical benefits outweigh the potential disadvantages (health anxiety, risk of over-diagnosis, costs) and to determine the optimal and most cost-effective screening approach in the face of rapidly developing and widely accessible technologies.

Complete AF management should also address the fear and avoidance behaviour that intrusive AF symptoms can induce which in turn contributes to impaired quality of life and high healthcare use.

Written by Dr Christine A’Court and Dr Charles Gardiner, who are GP Cardiologists at the John Radcliffe Hospital, Oxford