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					Non-Pharmacological Treatment of Atrial Fibrillation

Non-Pharmacological Treatment of Atrial Fibrillation
Johann Christopher, Chandrakant B Chavan, C Narasimhan Department of Cardiology, CARE Hospitals, The Institute of Medical Sciences, Hyderabad

INTRODUCTION
The goal of therapy in atrial fibrillation (AF) is to reduce the risk of stroke. At present, most patients with AF are treated with either a rhythm or rate control strategy. This article outlines the current non-pharmacological management strategies for AF including catheter ablation, surgery, pacing and atrial defibrillators. Catheter ablation and surgical techniques for AF will be the focus of this article.

Pathophysiology of Atrial Fibrillation
Premature ectopic beats predominantly originating from the pulmonary veins (PVs), multiple wavelets and rotors have all been implicated in the genesis of AF making it a complex arrhythmia to understand.

Radiofrequency Catheter Ablation for Atrial Fibrillation
Better understanding of the electrophysiology of AF from experimental work combined with findings from the catheterization laboratory has led to effective treatment for AF. Effective control of AF was initially possible by open heart surgery and the Maze procedure.6 Performing a catheter-based Maze procedure for the control of AF was unsuccessful but led to the finding that in a large proportion of patients AF was triggered by ectopy originating in the pulmonary veins. It was observed that extensive ablation in the left atrium (LA) was associated with a risk of stroke. Ablation within the pulmonary veins was also shown to result in pulmonary vein stenosis. The target area for ablation has therefore moved to the atrial aspect of the pulmonary veins with improved results and reduced complications. The two principal techniques that have gained the most widespread acceptance are: the pulmonary vein isolation (PVI) as pioneered by the group in Bordeaux, and the left atrial circumferential ablation (LACA) technique as developed in Milan by Carlo Pappone.7,8 Catheter ablation is certainly a treatment that should be considered for all symptomatic AF patients and those not adequately controlled by, or currently on antiarrhythmic medications, and for those who are intolerant to anti-arrhythmic drugs.

Rate vs Rhythm Control
Atrial fibrillation is usually associated with structural heart disease. Patients with AF are known to have an increased risk of mortality.1 Therefore it is considered logical to restore sinus rhythm. However, restoration of sinus rhythm was not necessarily free from risks. The most important risk is proarrhythmia from antiarrhythmic drugs.2 Randomized trials such as AFFIRM3 and RACE4 have shown that there was no difference in the primary outcomes of death and stroke during the time of discharge and follow-up. The survival advantage of restoration of sinus rhythm is negated by the side effects of antiarrhythmic drug therapy. This resulted in a surprising finding of similar clinical outcomes with either a rate control or rhythm control strategy. Safe and effective alternatives to antiarrhythmic drug therapy for the maintenance of sinus rhythm should possibly answer the rate versus rhythm controversy more clearly. There was a slight increase in strokes in the rhythm control group, which was attributed to the tendency to withdraw anticoagulation when patients appeared to be stable in sinus rhythm. This emphasizes the need for chronic anticoagulation in patients with atrial fibrillation despite restoring sinus rhythm with pharmacological therapy or electrical cardioversion.5 These observations also apply to patients with paroxysmal AF, most of whom have a risk of stroke that is similar to patients with chronic AF.

CATHETER ABLATION TECHNIQUES
These techniques include : (i) ablation of atrial fibrillation triggers, (ii) PV isolation, (iii) PV isolation + linear lesions,

Correspondence: Dr Johann Christopher, Department of Cardiology, CARE Hospitals, The Institute of Medical Sciences, Hyderabad E-mail: calambur@hotmail.com

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and (iv) WACA-wide area atrial compartmentalization lesions as advocated by Pappone and Morady.

Ablation of Triggers
Earlier studies relied on identification and ablation of ectopic beats initiating AF. Over 50% of patients were cured of their arrhythmia; however 70% required multiple ablations. First, the arrhythmogenic PV must be identified. Multipolar electrode catheters are placed sequentially in each vein, or multiple catheters are placed in multiple veins simultaneously. 9 If the sequence of PV activation follows a pattern of distal electrode (deep in the vein) to proximal electrode (at the base of the vein or in the LA), one may conclude that the source of activation of that beat arises from within the vein. Once the source of the ectopic activity has been identified, mapping within that vein can proceed. Local electrical activation timing measured from multipolar catheters positioned in the pulmonary veins is compared with the onset of the premature atrial complex (PAC), P-wave on the surface ECG. If a site of very early activation is reliably recorded, point ablation at this site can be curative. It is important to witness frequent discharges of the arrhythmogenic focus for successful use of this strategy. Limitations: In most patients discharges from the atria are infrequent making detailed activation mapping difficult. Inadvertent bumping of the focus during mapping may cause temporary stunning and inhibition of local activity.

variability among the origin and branching of the PVs.12,13 Electrical connections are then identified by the sharp high frequency PV potentials in the Lasso recordings. Radiofrequency (RF) energy is delivered on the atrial aspect of the Lasso catheter. Electrical disconnection of the PV is identified by disappearance of PV potential in the Lasso catheter. Map-guided PV isolation: Although the amount of RF energy applied to each vein was similar, PVs were isolated significantly faster and with less fluoroscopy exposure using an anatomically guided approach. Moreover, there were frequent cross-overs from the map-guided to the anatomical approach, but not the other way around. Several tools provide the anatomical details to navigate and ablate close to the LA-PV junction. Intracardiac echocardiography, three-dimensional (3D) electroanatomic mapping system like CARTO, Navex help to identify the site of ablation and to create contiguous lesions.
Pulmonary Vein Ostial Isolation
Segmental Complete

SVC RA IAS

RSPV

LSPV

LA
RIPV

IVC

LIPV

Pulmonary Vein Isolation (Figure 1)
After the initial experience it became apparent that precise mapping of individual arrhythmogenic foci inside PV is impractical and time-consuming. The firing of the focus can be infrequent and unpredictable, and there may be multiple foci arising from the same or different veins.10 Further, ablation deep inside distal, narrower segments of PV can increase the risk of PV stenosis.11 Secondly, AF recurred from either the same or a different PV. Complete electrical isolation of the PV emerged as a preferred approach to ablation of AF with a focal origin. Anatomical and electrophysiological studies revealed muscular connections between the LA and the PVs are present only in certain segments of the ostium of PV, and not all along the circumference of PV. This resulted in the concept of segmental ostial isolation. There are two main components of the PV isolation procedure. First is to identify the ostium of the PVs. Initially a circular mapping catheter (Lasso) is positioned at the ostium of the PV. Since the procedure is anatomically guided, it is important to determine the location and anatomy of the ostia of pulmonary veins and main branches. It is important to realize a marked anatomical
2
Figure 1. Pulmonary vein ostial isolation. SVC: superior vena cava; RA: right atrium; IAS: interatrial septum; RSPV: right superior pulmoary vein; RIPV: right inferior pulmonary vein; LSPV: left superior pulmonary vein; LIPV: left inferior pulmonary vein

PV Isolation + Linear Lesions (Figure 1)
Ideally, a combination of PV isolation and linear ablation would be expected to yield the highest efficacy.14,15 This approach not only prevents activation of the atria from triggering foci in the pulmonary veins, but it excludes a region of atrial myocardium, thus eliminating those regions as potential sites of re-entry. The design of the ablation lines varies. Nademanee et al. 16 observed that complex fractionated electrograms recorded from the distal bipole of the ablation catheter were indicative of the electrical substrate for maintenance of AF. Catheter ablation of these sites resulted in higher success rate. Advantages: First, there is no risk of PV stenosis, because the ablation is performed outside the veins on the LA-free wall. Second, it is possible to better isolate from the LA potentially arrhythmogenic PV-LA junction. This region of
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the LA appears to be a common site for rapid electrical activity during AF,17,18 and may be an anatomical substrate that favors stable rotor formation. Third, excluding larger areas of the LA leads to diminution of the area of the LA that is available for maintenance of AF. Disadvantages: The disadvantages of the method stem primarily from the time required to create a complete lesion set, the difficulties in assuring continuity and transmurality of the ablative lines, and the possibility of a proarrhythmic complication from creation of linear lesions that could be the substrate for new macro re-entrant tachycardia.

WACA-Wide Atrial Compartmentalization Lesions as Advocated by Pappone and Morady (Figure 2)
Compartmentalization or debulking of the atria improves procedure efficacy by disrupting the substrate for re-entrant AF propagation, even in the presence of persisting triggers. Achieving transmural lesions appears to be an important step in linear ablation. Non-transmural (or nonoverlapping) lesions are sources of gaps that can serve as substrates for atrial macro re-entry and lead to emergence of new, difficult-to-treat arrhythmias. In addition, these procedures are time consuming. A recent comparison of the two techniques by another group has suggested a slightly higher efficacy of LACA over PVI,19 although the recent addition of linear ablation in the left atrium to PVI has further increased its effectiveness. These two pioneering groups are reporting cure rates of up to 90% for patients with paroxysmal AF and slightly lower rates of success for patients with persistent AF. The Bordeaux group has shown that in patients with heart failure and AF, PVI improves left ventricular (LV) function, heart failure symptoms, and quality of life.20 Although neither of these studies were randomized, they provide promising initial evidence that ablation for AF is safe and may reduce mortality rates. In this respect ablation seems to have an advantage over pharmacological rhythm control (Figure 2). Basket and non-contact catheter mapping: Infrequent episodes of spontaneous AF initiation or PACs can increase the difficulty of activation mapping and map-guided focal ablation. To decrease mapping time and increase mapping accuracy, multi-electrode 3D mapping systems have been employed. These techniques make it possible to acquire an activation map from the whole endocardial surface from a single beat and determine the site of earliest activation. This can guide ablation procedure, increasing precision of application and possibly decreasing total amount of RF energy and fluoroscopy time.

Figure 2. Schematic diagram of the atria and great veins. Dotted lines indicate lesions used for LACA and dark lines depict the lesion sets in patients with persistent /chronic atrial fibrillation. LACA: left atrial circumferential ablation; SVC: superior vena cava; RA: right atrium; IAS: interatrial septum; RSPV: right superior pulmoary vein; RIPV: right inferior pulmonary vein; LSPV: left superior pulmonary vein; LIPV: left inferior pulmonary vein

PATIENT SELECTION
Indications 1. AF ablation in symptomatic patients with paroxysmal AF who have no, or only mild structural heart disease. In this group, the procedural success is higher and fewer complications are expected. 2. The intermediate group (i.e., patients with moderate structural heart disease and persistent AF) is more an object of controversy. As a policy, we try medical therapy after adequate correction of the underlying heart disease. We prefer ablative approach only if patients are highly symptomatic despite medical therapy. Contraindications The procedure is contraindicated in patients with symptoms that are vague and are not attributable to arrhythmia. Finally, AF ablation is unlikely to benefit those with infrequent and well-tolerated AF episodes, or those whose prognosis or quality of life are compromised by other medical conditions.

Procedure-related Complications
Complications from AF ablation procedures can be divided into three main categories. 1. Those common to all invasive cardiac procedures, for example bleeding, hematomas, vascular complications, and cardiac perforation with tamponade.

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2. Those encountered during left-sided ablations, for example complications of transseptal puncture, valve injury caused by catheter entrapment, embolic stroke. 3. Those specific to PV ablation or linear atrial ablation, and include pericarditis from thermal injury,21 esophageal injury,22 PV stenosis,23 and proarrhythmia with atrial reentrant tachycardias arising from incomplete linear ablations. The events from the first two groups are defined in literature with the complication rates being quite low. The complication of greatest concern is procedure-related stroke.11 This serious complication can be minimized with continuous anticoagulation, careful regulation of RF power delivery, and meticulous sheath management, but it is unlikely that the prevalence of stroke will fall below 0.5%. Catheter ablation of the AV node followed by pacemaker implantation is a useful therapy for ventricular rate control in selected group of patients. This approach is indicated in patients in whom ventricular rate control is poor despite drug therapy. Atrium continues to be fibrillating , therefore anticoagulation needs to be continued.

approach to preventing AF.27,28 In a series of 12 patients with chronic AF who underwent mitral valve surgery, intraoperative atrial mapping showed regular and repetitive activation in the left atrium in 9; surgical isolation of the pulmonary vein orifices resulted in restoration of sinus rhythm in all of these patients.29 Impact on stroke: since the maze operation frequently restores sinus rhythm in patients with chronic AF, it may also prevent stroke. In most patients left atrial appendage (LAA) is the source of clot. Excision of LAA significantly reduces the risk. This issue was addressed in a review of 306 patients with medically refractory AF, 19% of whom had a history of a stroke.30,31 Perioperatively, a stroke occurred in 0.7%, while during follow-up of up to 11.5 years, a late minor stroke occurred in only one patient. The reduction in the incidence of stroke was related to the restoration and maintenance of sinus rhythm and atrial transport function and surgical removal or obliteration of the (LAA). Complications 1. Extensive damage to the atrial myocardium with resultant atrial dysfunction that may impair the LA transport function. 2. Sinus node dysfunction including severe sinus bradycardia, sinus pauses or sinus arrest, sinoatrial exit block, atrial tachyarrhythmias, alternating periods of atrial bradyarrhythmias, tachyarrhythmia and inappropriate heart rate responses during exercise or emotional stress. 4. Radiofrequency or cryoablation during surgery: The use of RF energy or less often cryoablation during cardiac surgery to create linear endocardial lesions that interrupt AF (sometimes called the “RF maze” procedure) is less time-consuming and easier than the surgical maze procedure. Limited linear ablation in the left atrium is as effective as the biatrial technique and produces less atrial damage.32

SURGICAL TREATMENT
Several surgical techniques have been developed for the control of refractory AF and maintenance of sinus rhythm. These techniques are mostly employed as adjunctive therapy in patients who undergo other cardiac surgery for some other reason (valve repair or replacement, coronary bypass grafting, or corrective surgery for congenital heart disease). 1. Maze operation: In the “maze” operation developed by Cox, several small incisions are made in the right and left atria to interrupt the potential reentrant pathways required for AF maintenance. In a 5-year experience of 75 patients in one center, the procedure cured AF, restored AV synchrony, and preserved atrial transport function in all but one patient; six(9%) patients required antiarrhythmic medications.24 Postoperative atrial pacemakers were implanted in 40%, mostly for pre-operative sick sinus syndrome but occasionally for iatrogenic sinus node injury. Significant improvement in quality of life was also reported.25 Radial approach: The radial approach was developed to provide a more physiologic atrial activationcontraction sequence, thereby reducing the degree of left atrial dysfunction and optimizing the atrial contribution to LV filling.26 Pulmonary vein isolation: The observation that ectopic beats originating from foci around the pulmonary veins can trigger AF suggests that isolation of the pulmonary vein orifices may be an effective

2.

Comparison with surgical maze: The use of linear RF ablation is at least as effective as the surgical maze procedure in restoring sinus rhythm. This was shown in a review of 70 patients, of whom 40 underwent RF ablation and 30 underwent the surgical maze procedure.26 Those undergoing RF ablation and those undergoing the surgical maze had similar rates of sinus rhythm at discharge (85 vs 73%) and at one year (91 vs 96%).

3.

CONCLUSIONS
There exists a spectrum of AF and therefore a wide variety of approaches to ablative therapy. On one end of the

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spectrum are patients with normal hearts, normal atrial size, and frequent paroxysms of AF. These patients probably have a focal mechanism of AF and should be treated with focal ablation techniques or PV isolation. The success rate is likely to be high with a low reccurence rate. On the other end of the spectrum are patients with structural heart disease, significant atrial enlargement, and persistent or permanent AF. The arrhythmia mechanism in these cases is most likely re-entry with a single or multiple rotors of electrical activity in the LA. A more aggressive linear ablation procedure is being practiced in these cases. However, the success rates with catheter ablation is likely to be modest, with higher recurrence and complication rate. Between the two extremes are those who may have mild structural heart disease (e.g., hypertensive heart disease), mild or moderate left atrial enlargement, runs of paroxysmal or persistent AF. In these cases elimination of the triggers of AF may be partially successful in preventing AF. Surgery for AF is now mainly indicated for patients with AF who require surgery for other cardiac conditions like mitral valve disease or coronary artery disease.

REFERENCES
1. Pappone, C, Oreto, G, Lamberti, F, et al. Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system. Circulation 1999; 100: 1203. 2. Marrouche, NF, Martin, DO, Wazni, O, et al. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation 2003; 107: 2710. 3. Atrial fibrillation follow-up investigation of rhythm management — the AFFIRM study design. The Planning and Steering Committees of the AFFIRM study for the NHLBI AFFIRM investigators. Am J Cardiol 1997; 79: 1198–1202. 4. Hagens VE, Van Gelder IC, Crijns HJ. Rate control versus electrical cardioversion of persistent atrial fibrillation (RACE) Study Group. Card Electrophysiol Rev 2003; 7: 118–21. 5. Moe GK, Abildskov JA. Atrial fibrillation as a self-sustaining arrhythmia independent of focal discharge. Hertz 1959; 8: 59–70. 6. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659–66. 7. Pappone C, Oreto G, Rosiano S, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 2001; 104: 2539–44. 8. Oral H, Scharf C, Chugh A, et al. Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 2003; 108: 2355–60. 9. Chen SA, Hsieh MH, Tai CT, et al. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation. Circulation 1999; 100: 1879–86. 10. Haissaguerre M, Jais P, Shah DC, et al. Catheter ablation of chronic atrial fibrillation targeting the reinitiating triggers. J Cardiovasc Electrophysiol 1999; 11: 2. 11. Robbins IM, Colvin EV, Doyle TP, et al. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation 1998; 98: 1769– 75. 12. Ho SY, Sanchez-quintana D, Cabrera JA, et al. Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation.

J Cardiovasc Electrophysiol 1999; 10: 1525–33. 13. Scharf C, Sneider M, Case I, et al. Anatomy of the pulmonary veins in patients with atrial fibrillation and effects of segmental ostial ablation analyzed by computed tomography. J Cardiovasc Electrophysiol 2003; 14: 150–55. 14. Ernst S, Schluter M, Ouyang F, et al. Modification of the substrate for maintenance of idiopathic human atrial fibrillation: efficacy of radiofrequency ablation using nonfluoroscopic catheter guidance. Circulation 1999; 100: 2085–92. 15. Schwartzman D, Wackowski C, Shafenberg C. Outcome of right atrial linear radiofrequency ablation for suppression of atrial fibrillation. PACE 1999; 22: 904. 16. Nademanee K, McKenzie J, Kosar E, et al. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol 2004; 43: 2044–53. 17. Arora R, Verheule S, Scott l, et al. Arrhythmogenic substrate of the pulmonary veins assessed by high-resolution optical mapping. Circulation 2003; 107: 1816–21. 18. Nakashima H, Kumagai K, Tojo H, et al. Simultaneous catheter mapping of the pulmonary veins in focal atrial fibrillation: significance of rapid focal activation, effectiveness for catheter ablation. Jpn Heart J 2002; 43: 357–65. 19. Seidl K, Schwacke H, Zahn R, et al. Catheter ablation of chronic atrial fibrillation with noncontact mapping: are continuous linear lesions associated with ablation success? PACE 2003; 26: 534–43. 20. Hsu LF, Jais P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004; 351: 2373–83. 21. Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003; 42: 185–97. 22. Wood MA, Ellenbogen KA, Hall J, et al. Post-pericardiotomy syndrome following linear left atrial radiofrequency ablation. J Interv Card Electrophysiol 2003; 9: 55–57. 23. Patwardhan AM, Lad VS, Pai V. Oesophageal injury during radiofrequency ablation for atrial fibrillation: inherent safety of radiofrequency bipolar coagulation. J Thorac Cardiovasc Surg 2002; 124: 642–43. 24. Kok LC, Mangrum JM, Haines DE, et al. Cerebrovascular complication associated with pulmonary vein ablation. J Cardiovasc Electrophysiol 2002; 13: 764–67. 25. Chiappini, B, Martin-Suarez S, LoForte A, et al. Cox/Maze III operation versus radiofrequency ablation for the surgical treatment of atrial fibrillation: a comparative study. Ann Thorac Surg 2004; 77: 87. 26. Leitch JW, Klein G, Yee R, Guiraudon G. Sinus node-atrioventricular node isolation: long term results with the “corridor” operation for atrial fibrillation. J Am Coll Cardiol 1991; 17: 970. 27. Nitta T, Ishii Y, Ogasawara H, et al. Initial experience with the radial incision approach for atrial fibrillation. Ann Thorac Surg 1999; 68: 805. 28. Sueda T, Imai K, Ishii O, et al. Efficacy of pulmonary vein isolation for the elimination of chronic atrial fibrillation in cardiac valvular surgery. Ann Thorac Surg 2001; 71: 1189. 29. Mazzitelli D, Park CH, Park KY, et al. Epicardial ablation of atrial fibrillation on the beating heart without cardiopulmonary bypass. Ann Thorac Surg 2002; 73: 320. 30. Cox JL, Ad N, Palazzo T. Impact of the maze procedure on the stroke rate in patients with atrial fibrillation. J Thorac Cardiovasc Surg 1999; 118: 833. 31. Pasic M, Musci M, Siniawski H, et al. The Cox maze III procedure: parallel normalization of sinus node dysfunction, improvement of atrial function, and recovery of the cardiac autonomic nervous system. J Thorac Cardiovasc Surg 1999; 118: 287. 32. Deneke T, Khargi K, Grewe PH, et al. Left atrial versus bi-atrial Maze operation using intraoperatively cooled-tip radiofrequency ablation in patients undergoing open heart surgery: safety and efficacy. J Am Coll Cardiol 2002; 39: 1644.

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Description: Atrial fibrillation (AF or afib) is a cardiac arrhythmia (abnormal heart rhythm) that involves the two upper chambers (atria) of the heart.