Making Sense of Atrial Fibrillation (AF)

- An Introduction to the Ablation of Atrial Fibrillation.

“During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from a highly experimental unproven procedure, to its current status as a commonly performed ablation procedure in many major hospitals throughout the world”.

- HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation¹

AF is a supraventricular tachycardia characterized by uncoordinated atrial activation with loss of atrial mechanical function. The ECG in AF shows irregular fibrillatory waves instead of organised p waves and an irregular ventricular response.

Catheter ablation of AF has been the “Holy Grail” of EP over recent decades. Why is this, why has an ablative cure been difficult to achieve and how does AF ablation work?

AF: The Problem

AF affects a lot of people and costs a lot of money. It is the most common clinically significant cardiac arrhythmia accounting for over one third of hospitalisations for a cardiac rhythm disturbance2 and a quarter of the population will develop AF during their lifetime.3 In 2000 a staggering 1% of the UK National Health Service budget was spent on AF (€ 688 million).4 Many patients experience intolerable symptoms during AF.

It is the most frequent sustained arrhythmia and increases with each decade of life, approaching 5% in pts over 60 and some 9% in those over 80. The cardiovascular effects of AF are many and include decrease in stroke volume, increased LA pressure and volume, loss of atrial systole, shortened diastolic ventricular filling period and AV valvular regurgitation. AF is associated with approximately 10-15% of all strokes5 due to stasis of blood in a non-contractile left atrium and is a confounding factor in the treatment of 20-26% of all heart failure patients.3

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Rationale for AF Ablation

The primary justification for an AF ablation procedure is to improve quality of life -ablation is currently indicated in patients with symptomatic drug refractory AF.
There are broadly two approaches to the treatment of patients with AF, ablation aiming at rhythm control.

Rhythm control seeks restoration & maintenance of sinus rhythm (SR). Drugs, permanent pacing and ablation have all been utilised in an attempt to restore and preserve sinus rhythm.

Rate control seeks to control symptoms from AF by restricting the fluctuations in heart rate typical of this arrhythmia. Rate slowing drugs can be used to limit the severity of tachycardia during fast AF, but in some patients theses encourage bradycardia which, if symptomatic requires pacemaker insertion. Despite optimal medical rate control many patients still experience debilitating symptoms. In the past, catheter ablation or modification of the AV junction was a common procedure to restrict fast ventricular rates during AF in patients where rate slowing medications failed. The need for permanent pacemaker implantation and the success of catheter AF ablation now restrict AV node ablation to patients with permanent AF.

There have been several randomized clinical trials that address whether rate or rhythm control is more beneficial for AF patients. These trials show that using antiarrhythmic drugs to maintain SR does not realise the potential benefits. An analysis of the AFFIRM study - one of the largest, suggests that a beneficial effect on survival of restoring sinus rhythm is being masked by the adverse effects of antiarrhythmic drugs. This analysis reveals that the presence of sinus rhythm is associated with a 47% lower risk of death but use of antiarrhythmic drugs increased mortality by 49% effectively cancelling out the benefit. The conclusion is that restoration of, and maintenance of SR is of potential benefit if it can be achieved without the use of anti-arrhythmic drugs – i.e. by ablation. The results of recent studies suggest there are benefits to sinus rhythm obtained by ablation techniques over rate control.1 The recognition that AF, once initiated, alters atrial electrophysiological properties in a manner favouring the induction and maintenance of the arrhythmia (AF begets AF)6 provides additional impetus for early intervention to maintain SR.

Efficacy of AF Ablation

There is now substantial evidence for the efficacy of catheter ablation.1
Outcomes vary considerably however, influenced by differences in technique, experience and technical proficiency. Differences in follow-up, definitions of success and variation in the use of antiarrhythmic therapy also affect reported outcomes.1, A worldwide survey on the methods, efficacy, and safety of catheter ablation of AF was published in 2005.7 The success rate, defined as freedom from symptomatic AF in the absence of antiarrhythmic drug therapy, was 52%. An additional 24% of patients were free of symptomatic AF in the presence of a previously ineffective antiarrhythmic.. More than one ablation procedure was performed in 27% of patients.

There is a body of evidence for additional benefits, such as decreased stroke risk, decreased heart failure risk, and improved survival - but they have not yet been systematically evaluated as part of a large randomized clinical trial.

The incidence of major complications in the 2005 study was 6%. The left atrium (LA) harbours the majority of AF sources and so AF ablation requires transeptal puncture – introducing risk of tamponade. Other risks include PV stenosis, phrenic nerve damage and oesophageal fistula.

Mechanisms of Atrial Fibrillation

AF is different to other tachycardias treated in the EP lab. It is more complex and appears chaotic. Despite considerable progress having been made in recent years the mechanisms of initiation and perpetuation of AF they remain incompletely understood.

For many years, three major schools of thought competed to explain the mechanism(s) of AF:

• Multiple, random propagating wavelets - multiple wavelet hypothesis

• Focal electrical discharges

• Localized re-entrant activity with fibrillatory conduction.

All three are now thought to play a role but until the mid to late 1980s, the multiple wavelet hypothesis proposed by Moe and colleagues was widely accepted as the dominant AF mechanism and provided the intellectual foundation for attempts at surgical and catheter ablation. The hypothesis asserts that AF requires a critical number of circulating re-entrant wavelets, each of which requires a critical mass of atrial tissue. In other arrhythmias such as atrial flutter the re-entrant circuit has a fixed anatomical location and so lesions placed across a critical isthmus lead to termination and cure. If AF is a more random process with meandering and unstable re-entrant circuits and no definable critical location, lesions based on electrophysiological mapping will have no effect. However a series of continuous lesions that compartmentalize the enlarged atria, forming barriers to interrupt potential wavefronts might be effective. In the late 80s Cox and colleagues performed a series of very successful operations based on this principle – the Maze procedure. Unfortunately this required a thoracotomy and could lead to loss of atrial mechanical function and sinus node damage requiring a pacemaker. The surgical incisions were extremely difficult to replicate with catheter ablation, particularly with technical limitations of that era.

Importance of the Pulmonary Veins

The development of AF requires both a trigger and a susceptible substrate.
The goals of AF ablation procedures are to prevent AF by either eliminating the trigger that initiates AF or by altering the arrhythmogenic substrate (or both).

Tachycardias treated by ablation are usually split into re-entrant and focal. Focal tachycardias result from localised regions of tissue behaving abnormally – firing off rapid impulses instead of being depolarised by an external impulse originating from the SA node. Re-entrant rhythms consist of “endless loops” of activation where the advancing wave can return to the starting point, similar to a Mexican wave. However, the distinction is not straightforward as re-entrant arrhythmias are often initiated by premature ectopic beats from an automatic or triggered focus. The ectopic is focal but it triggers a sustained re-entrant tachycardia.

A great advance was the observation by Haissaguerre and colleagues that in a subset of patients AF was initiated and in some cases maintained by rapid ectopic beats which were not randomly distributed but were concentrated at the four pulmonary veins (PVs). In a landmark paper in 1998 Haissaguerre concluded that the pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of AF and that these foci respond to treatment with RF ablation. 8

It is now well established that the PVs are a crucial source of triggers which initiate AF are mark the beginning of the modern era of AF ablation.

Focal ablation

Early focal AF ablations sought to observe spontaneous ectopics triggering AF, identify the focal source and eliminate it by ablation. The procedure was successful in some patients but had drawbacks. Although patients with frequent ectopy were selected, the ectopy could only be mapped if it occured at the time of the procedure. Many foci were ablated deep within the PVs causing PV
stenosis9 sometimes resulting in pulmonary hypertension. These drawbacks lead to a new approach – pulmonary vein isolation.

Pulmonary Vein Isolation

Pulmonary vein isolation (PVI) prevents potential AF initiators from exiting the vein by electrically disconnecting the PVs from the left atrium by ablation.

Ablation strategies which target the PVs and/or PV-LA junction are now the cornerstone for most AF ablation procedures. Today the primary aim of ablation is electrical isolation of the PVs by creation of circumferential lesions around the PV ostia, avoiding ablation within the PVs.

Circumferential lesions also modify the AF substrate by a variety of means including elimination of tissue near the atrial–PV junction that provides a substrate for re-entrant circuits, reduction of the mass of atrial tissue which would otherwise be available to sustain re-entry1 and ablation of epicardial autonomic ganglia that are implicated in AF initiation.

In patients with persistent AF and particularly those with longstanding persistent AF, ostial PV isolation alone may not be sufficient. Inclusion of the atrial myocardium in ablation strategies is particularly important in these
patients.

References

1. Calkins H, Brugada J, Packer DL et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up Heart Rhythm, 2007; Vol 4, No 6,

2. Bialy D, Lehmann MH, Schumacher DN, Steinman RT, Meissner MD. Hospitalization for Arrhythmias in the United States: Importance of Atrial Fibrillation [abstr]. J Am Coll Cardiol. 1992; 19: 41A.

3. Benjamin E.J., Levy D, et al. Independent risk factors for atrial fibrillation in a population-based cohort; The Framingham Heart Study JAMA 1994; 271(11):840-844.

4. Stewart, S. et al. “Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK.” Heart 90.3 (2004): 286-92

5. Stafford R.S., Robson D.C., et al. Rate control and sinus rhythm maintenance in atrial fibrillation: National trends in medication use. Arch Intern Med 1998; 158: 2144-2148.

6. Wijffels et al:Atrial Fibrillation begets Atrial Fibrillation. Circulation 92, 1954-1968(1995)

7. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005;111:1100– 1105.

8. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le MA, Le MP, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659–666.

9. Ernst et al. Total pulmonary vein occlusion as a consequence of catheter ablation of atrial fibrillation. European Heart Journal Vol.22, Abstr.Suppl. September 2001:p244, Abstr1322