The right and left atria are two complex cardiac chambers with the role of collecting venous blood from the body and the lungs, respectively, before contracting to augment the passive filling of the ventricles. This contraction is initiated and co-ordinated by the electrical conduction system of the heart. An important abnormality of heart rhythm is atrial fibrillation (AF), affecting 1–2% of the adult population. This irregular contraction of the atria results in loss of the augmented left ventricular filling with a reduction in cardiac output of 20–50%. AF was first described over 100 years ago, but only recently has a more complete understanding of the mechanisms behind AF enabled more successful treatment. Patients complain of shortness of breath, palpitations and reduced exercise tolerance. A doubling in cardiac mortality is seen with the highest rates in those with heart failure. Patients are also at an increased risk of stroke.1 When the atrial tissue is in some way abnormal – usually due to underlying disease (termed abnormal substrate) producing fibrosis or dilatation – triggers can initiate AF. These require termination by medical intervention. Experimental models of AF demonstrate two phenomena. First, repetitive reinduction of AF in the normal heart produces AF of increasing duration until it becomes sustained (electrical remodelling), and this also results in dilatation of the atria (mechanical remodelling), which further promotes AF.2 Second, the rate of the AF in the atria is not constant, but rather is more rapid in the posterior left atrium adjacent to the pulmonary veins (PVs).3 This observation led to the discovery of rapidly firing foci in the PVs, which act as triggers for initiating and sustaining AF in a manner similar to the experimental models.
Recent Advances
Initial attempts to restore normal sinus rhythm are often successful, although attempts to do so reduce after time. Electrical cardioversion involving the passage of an electrical direct current (DC) shock across the chest wall to restore sinus rhythm is often used as an initial treatment. The introduction of biphasic defibrillators has increased success rates to up to 90%, making this a very successful treatment.4 However, relapse rates of 60% over two years with an early (within one month) relapse rate of 40% are common.5 This can be improved to rates of relapse of 40% over two years with antiarrhythmics to stabilise the atrial rhythm. The main limitations of antiarrhythmics remain the risk of ventricular pro-arrhythmia (placing the patient at risk of sudden death), their negative ionotropic properties (decreasing cardiac output) and peripheral side effects such as pulmonary fibrosis and thyroid dysfunction, which limit their long-term use and preclude their use in some patients – such as those with airways disease or very severe heart disease.
The risk of pro-arrhythmia relates mainly to the potassium-current-blocking properties of these drugs in the ventricles, a site of action not necessary for their antiarrhythmic effect. Newer antiarrhythmics such as RDS12356 and AVE01187 target receptors specific to atrial tissue with a high efficacy and broad therapeutic index, and are currently in phase III trials.
Many cardiac diseases produce changes in the atrial muscle (substrate changes) such as fibrosis and dilatation. Some interventions aimed at preventing these changes or reversing them – drugs such as those with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARB) II,8 aldosterone antagonists and statins9 – produce small but incremental reductions in rates of AF.
That the PVs fire rapidly to produce AF means that the left atrium drives the AF. This realisation has led to catheter- and surgical-based attempts to isolate the PVs from the heart electrically and restore sinus rhythm. This is achieved by applying radiofrequency energy to the junction of the PVs and atrium, electrically isolating the veins from the heart.10 In patients with paroxysmal AF, this has borne promising results, but also an appreciation that, more rarely, other areas of the heart may have similar foci.
Isolation of the PVs is technically challenging. Late electrical reconnection is common and accounts for a significant proportion of relapses. Attempts to improve results have focused on improved anatomical definition with the use of mapping systems integrating computed tomography (CT) of the heart with electro-anatomical mapping and the use of alternative energy sources such as focused ultrasound and cryoablation (freezing to denature tissue).11
In other patients with permanent AF this limited ablation is less successful, reflecting more advanced change in substrate. The placement of additional lines in the left atrium has improved results. This has the effect of electrically compartmentalising the atria, preventing the circulation of AF but also disconnecting adjacent structures – such as the coronary sinus – from the atria, further reducing the mass of atrial tissue that can sustain AF. Currently, the optimal place for additional ablation lines remains unclear, but the roof of the left atrium, the coronary sinus and the intra-atrial septum appear important. This success is partly the result of a better understanding of the underlying mechanisms of AF, but also the application of increasingly sophisticated mapping systems such as the CARTO® XP system, allowing visualisation of the cardiac chambers without the need for prolonged X-ray exposure for patient and physician.12
The construction of virtual anatomies by these systems can be augmented by the integration of pre-procedure CT and magnetic resonance (MR) scans, allowing more detailed definition of cardiac anatomy (CARTOMERGE™ Image Intergration Module Software).
Tools for AF ablation form a very important part of the procedure and have improved success rates and safety. Intracardiac ultrasound such as the AcuNav™ catheter can be used for placement of transeptal catheters and to monitor the formation of intracardiac clot. Specialised catheters for circumferential mapping of the PVs help delineate the PV ostium and ensure electrical isolation. For patients with self-terminating (paroxysmal) AF, success rates of 80–90% have been established in several large series. For those with permanent AF, the more extensive ablation needed is associated with cure rates of 60–80%.12 Importantly, those with heart failure – a group with high mortality rates – have been demonstrated to benefit from a reduced mortality rate when undergoing catheter ablation compared with standard medical management.13 What limits AF ablation at the present time is the lack of hard end-points for this procedure, as well as incomplete lines of ablation, which may worsen the condition they are trying to treat. Success rates for atrial flutter ablation rose by 60–90% with the realisation of reproducible electrophysiological end-points. The expectation must be that similar improvements will occur in AF ablation.
However, some risks remain with AF ablation, such as the 1% incidence of stroke and cardiac perforation, which restricts its use as a first-line procedure.12 Many patients undergoing cardiac surgery for coronary artery and valvular heart disease have concomitant AF. When the chest is open, surgical ablation of AF adds little mortality or morbidity to the procedure. The sheer number of patients affected by AF and the expensive and time-consuming nature of ablation for AF will restrict its use to those with symptomatic AF who have failed or decline initial medical management.
AF is associated with a doubling of the risk of stroke compared with age- and disease-matched controls.1 Effective treatment in the form of aspirin or anticoagulants is available, but the benefits in terms of stroke prevention need to be balanced against the increased risk of bleeding associated with their use. The increased thromboembolic risk associated with AF arises as a result of stasis of blood in the left atrium, and the left atrial appendage (LAA) in particular.14
Surgeons have routinely removed this area at the time of mitral valve replacement to avoid subsequent thromboembolism. A novel approach is to occlude the LAA percutaneously with a prosthetic device made of nitanol mesh. To date, two small trials – Watchman LAA occluder and percutaneous LAA transcatheter occlusion (PLAATO) device15,16 – have reported showing an absence of stroke in the treated groups and successful occlusion of the LAA at follow-up. This may, in the future, reduce the need for warfarinisation with its attendant risks in a large number of patients.
Summary
AF is a complex and common arrhythmia manifesting in a wide range of cardiac and non-cardiac conditions. Patients experience symptoms of shortness of breath and palpitations, which have a significant impact on quality of life. More concerning is the increased risk of stroke. Attempts to restore sinus rhythm are becoming increasingly successful as a result of refined algorithms for the use of existing drug treatment and the emergence of more atrial-specific agents, which modify substrate and exert specific atrial antiarrhythmic effects free of ventricular pro-arrhythmia. Ablation, using either a surgical or percutanous approach, has a very high success rate for those with paroxysmal AF, although its use as a first-line therapy is limited by the risk of stroke and thoracotomy. Refinements to ablation techniques for permanent AF – such as the use of advanced mapping – are producing encouraging results in terms of restoration of normal rhythm and also in the reduction in the complications associated with AF such as heart failure deaths.