Understanding the Electrophysiological Substrate Underlying Persistent Atrial Fibrillation Study II (USURP AF- Study II)'

There are an estimated 1.4 million people in the UK with atrial fibrillation (AF), which accounts for 2.4% of the adult population.1 It is well established that AF is a major causative factor for ischaemic stroke and systemic embolism.2 In addition, strokes resulting from AF carry the highest morbidity and mortality of any other form of stroke. AF is also associated with increased morbidity in relation to heart failure.3,4,5 The UK 2016/7 Sentinal Stroke National Audit Programme (SSNAP) reported that in 7,483 patients with known AF who were not anticoagulated before their stroke, there was a 26% mortality and 45% were discharged with moderate-severe disability.6 AF, therefore, is not only associated with increased mortality and morbidity but also significant healthcare costs.

Broadly speaking AF is characterized by a rapid erratic depolarization of the atrial myocardium which manifests clinically as an irregular pulse which can be rapid. This is diagnosed initially on clinical suspicion by palpation of the pulse and then definitively by an ECG which will show irregular intervals between the QRS complex and absence of a P-wave. Clinically patients may be asymptomatic, however typical associated symptoms include palpitations, (exertional) dyspnoea, syncope/presyncope and chest pains. The patient may experience a variation of these symptoms.

The classification of AF is dependent on several factors: presentation, duration and spontaneous termination. There are 5 defined patterns of AF: First diagnosed AF is that which has not been previously diagnosed irrespective of duration and severity of AF-related symptoms. Paroxysmal AF which self terminates, usually within 48 hours. This includes AF episodes which are cardioverted within 7 days. Persistent AF, which lasts longer than 7 days. Long standing persistent AF, continuous AF lasting >1 year when it is decided to adopt a rhythm control strategy. Permanent AF implies that AF has been accepted by both the patient and the physician, therefore there would be no further pursuit of rhythm control intervention. [2016 ESC Guidelines for the management of atrial fibrillation].

The management of AF is two-fold. Where clinically indicated the patient should be anticoagulated. Over the last seven years four non-VKA OACs (NOACs)-dabigatran, a direct thrombin inhibitor and rivaroxaban, apixaban and Edoxaban, factor Xa inhibitors-have been tested against warfarin in large randomised controlled trials.7-10 These NOACs have been shown to be at least as effective as warfarin in stroke prevention, with a superior safety profile, consistently reducing intracranial haemorrhage.11 Other practical advantages of the NOACs include very few drug interactions and a predictable onset and offset that eliminates the requirement for regular anticoagulation monitoring. This has led to the 2014 NICE AF Guideline giving an equal first-line recommendation for NOACs alongside warfarin for stroke prevention.12 NICE also recommends that the options for anticoagulation should be discussed with the patient and the choice should be based on their clinical features and preferences. The second treatment option is pursuit of either a rhythm or rate control strategy. Rate control is achieved via drug therapy. When aiming for rhythm control the option are 1) anti-arrhythmic drugs (AADs) or 2) Invasive catheter ablation.

At present, current AADs have limited efficacy in maintaining sinus rhythm in patients with AF. In addition, there side effect profiles may prevent their long term use in some patients, even where they are maintaining sinus rhythm.13 The most common drug used for maintenance of sinus rhythm is Amiodarone which carries a significant side effect profile. In particular there is a risk posed from long term use of thyroid dysfunction (hyper- or hypothyroidism), liver cirrhosis and lung fibrosis.