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Ablation of Atrial Fibrillation:
The Cleveland Clinic Experience

Nassir F. Marrouche, MD; Andrea Natale, MD

Division of Pacing and Electrophysiology, Department of Cardiology,
The Cleveland Clinic Foundation, Cleveland, Ohio, USA

INTRODUCTION
   Atrial fibrillation is the most common arrhythmia in clinical practice with an overall prevalence in the general population of 0.4% (1). Initial therapy of atrial fibrillation is directed toward revision to and maintenance of sinus rhythm, usually with the addition of antiarrhythmic therapy. However, even the best antiarrhythmic therapy is associated with only a 50 to 60% success rate of maintaining sinus rhythm after 1 year, and is associated with significant side effects including proarrhythmia, drug toxicity, and a possible increase in mortality (2). Catheter ablation of the AV node with subsequent pacemaker implantation can be useful to facilitate ventricular rate control, but atrial systole is not restored and thrombo-embolic risk is unchanged.

   As the understanding of the mechanisms of arrhythmias progresses, so does the ability to treat arrhythmias with catheter-based interventions (2). As we have seen in the past few years, each change in the mechanistic understanding of AF corresponded to an advancement in the treatment options.

   The hypothesis of a multiple wavelet theory of atrial fibrillation (3,4) led to the development of the surgical maze procedure (5,6). By making multiple linear scars in the atrium, the atrial chambers are compartmentalized in smaller regions unable to sustain AF. This technique, although successful, requires general anesthesia and open heart surgery. These important limitations have encouraged the development of catheter-based maze procedures.

   For the catheter-based maze a variety of tools have been used to make linear lesions in the atrium and interrupt the propagation of the wavelets (7-10). Several different approaches have been considered including epicardial linear lesions (11), the creation of right sided only linear lesions (9,12), both right and left sided linear lesions (7), and the use of different proprietary catheters. The use of three-dimensional electroanatomical mapping has been suggested to facilitate line placement and to insure continuity of the lesions as well (12,13). Due to the stroke risk with left-sided ablation, there was initial interest in right-sided only ablation (9,10,14). The initial enthusiasm was, however, mitigated by the overall poor results and long procedure time. Ultimately, despite the use of a variety of specially designed catheters the linear lesion approach have been nearly abandoned.

   That atrial fibrillation could be triggered from a rapidly firing single focus was first suggested by Scherf (15). However, it was not until recently that this concept was more fully explored. We now have evidence that in addition to the substrate needed for multiple wavelets there is a rapidly firing focus that initiates AF in the majority, if not all, cases. This is based on the pioneering work of Haissaguerre et. al. (16) who have demonstrated that in some patients atrial ectopic beats within the pulmonary veins are responsible for the initiation of spontaneous paroxysms of AF. This finding paved the way to different catheter-based treatment approaches. Focal ablation of the ectopic focus was initially considered.

   Haissaguerre and coworkers described their experience with their first 45 patients in a landmark study published in 1998 (16). Of the 45 patients, a single point of origin of atrial ectopic beats was found in 29 patients, two points in 9 patients and 3 or 4 points in 7 patients, for a total of 69 foci. One of the foci was in the posterior left atrium, 3 were in the right atrium, but the majority (94%) originated from the pulmonary veins (PV). Of those originating from the PV about half were from the left superior vein, a third from the right superior vein and the rest from the inferior veins with a predominant number coming from the left inferior vein. 62% of the patients had no recurrence of their AF in the 8±6 months of follow-up after ablation.

   Natale et al. reported their results with 48 patients who underwent focal AF ablation (17). All of the patients had persistent or chronic drug-refractory AF for a median of 3 years (range 1 to 6 years). In nearly 2/3 of the patients, the site of earliest activation of the atrial ectopic beats was from the pulmonary veins, with the left superior PV the most common. However, in 37% of the patients the earliest activation was in the right atrium, predominantly in the high and mid crista terminalis. During follow-up, sinus rhythm was successfully maintained in 40 patients (83%), but only 4 patients (8%) maintained sinus rhythm without any drug therapy. One patient experienced a transient ischemic attack 5 days after the ablation. Mainly two different strategies had been developed to map and eliminate pulmonary veins (PVs) triggers: focal ablation targeting single or multiple foci in the arrhythmogenic pulmonary vein trunk or electrical isolation of the PV by circumferential PV lesions.

   Recently, isolation of the PV applying segmental lesions at the site of the earliest conduction identified by circumferential mapping technique has been suggested to be effective (16). In our institution we have attempted isolation with 3 different approaches including: 1) lesions guided by a 3-dimentional non-fluoroscopic mapping system (CARTO) (18); 2) circumferential isolation delivering through-the-balloon ultrasound energy (19) (figure 1); 3) and more recently circumferential mapping of the pulmonary vein. The acute and chronic results with each approach are shown in table 1.

   Overall isolation with the CARTO system and the through-the-balloon ultrasound catheter achieved similar results. However, stenosis of the pulmonary vein was higher in the CARTO group. The most encouraging results were observed with circular mapping. With this approach one hundred and fifteen patients (80 men, mean age 53 ± 10 years) with symptomatic paroxysmal (65 patients), persistent (25 patients) or chronic (25 patients) atrial fibrillation (AF) (duration 5 ± 3 years) underwent catheter ablation. All antiarrhythmic drugs (AAD) (3 ± 0.8 drugs) were discontinued five half-lives prior to the ablation. Immediately prior to the procedure transesophageal echocardiography (TEE) was performed in all study patients. A spiral CT was performed two months after the procedure.

   Sixty-three patients presented to the electrophysiology laboratory in sinus rhythm (SR), 44 were in AF and 8 in atrial flutter/fibrillation. In 20 out of 63 patients in SR, spontaneous ectopies and AF were documented. DC cardioversion was followed by spontaneous reinitiation of AF in 31 of the 48 patients with sustained AF or flutter. Isoproterenol was required in 65% of patients (74/115) to initiate ectopies triggering AF. These included 44 patients presenting in SR and 17 patients initially in atrial flutter/fibrillation. Table 2 illustrates patients' characteristics.

PULMONARY VEIN ECTOPY
   Arrhythmogenic ectopic foci originated from a single vein in 64 patients. Firing from 2 veins occurred in 30 patients, from 3 veins in 17 patients and from 4 veins in 4 patients, for a total of 191 arrhythmogenic PV foci in 115 patients. This included 70 right upper pulmonary veins (RUPV), 90 left upper pulmonary veins (LUPV), 9 right lower pulmonary veins (RLPV) and 20 left lower pulmonary veins (LLPV).

   After defining the arrhythmogenic PV a custom made circular mapping catheter was deployed into that specific vein (Figure 2). Simultaneous circular and longitudinal mapping of the same PV appeared to support spiral conduction of activation during sinus rhythm and APCs distal to the ostium and a more uniform longitudinal activation at the ostium.

DISTAL AND OSTIAL ISOLATION
   Distal isolation (>5 mm from LA-PV) was performed in the first 21 patients. This approach was considered because the circular catheter was more stable when distally deployed. Lesions were delivered targeting the site with the earliest pulmonary vein local activation on the circular mapping catheter in 34 arrhythmogenic PVs. RF energy was delivered 6 ± 2 mm into the RUPV, 5 ± 2 mm into the LUPV, 7 mm into the RLPV and 6 ± 1 mm into the LLPV. A mean of 5 ± 2 RF (3±1 minutes) were needed for distal isolation.

   Ostial isolation was performed in 348 of the 360 treated PVs. In the initial 21 patients (34 PVs) ostial isolation was only performed in veins still capable of initiating ectopies and AF after distal isolation (24 out of 34 PVs). In 1 LUPV ostial isolation was not attempted due to evidence of nearly complete occlusion after distal ablation. In another patient the procedure was terminated due to evidence of neurologic embolic event before proximal isolation of the RUPV was achieved. In 10 PVs distal isolation eliminated ectopies initiating AF. To obtain ostial isolation a mean of 14 ± 4 radiofrequency lesions (8.6 ± 2 minutes) with 4 mm tip ablation catheter, a mean of 5 ± 2 (2 ± 1 minutes) radiofrequency lesions with 8 mm tip ablation catheter and a mean of 7 ± 4 radiofrequency lesions with the chilli ablation catheter. After distal isolation PV ectopies initiating AF from the treated vein were still present in 15 (71 %) out of 21 patients.

   After ostial isolation no APCs triggering AF were initiated from all but one PV despite an average infusion rate of isoproterenol of 14.3 ± 4.7 µg/min. In one patient isolation of a large RUPV ostium appeared difficult and was abandoned due to evidence of neurologic embolic event. The mean procedure and fluoroscopy time were 4±1 hours and 90 ± 30 min, respectively. The procedure time included the transesophageal echocardiogram performed in the laboratory before the ablation. Distal and ostial isolation data are represented in Table 3.

   Seventy five percent of patients (48 out of 75 patients) requiring isoproterenol for initiation of ectopies triggering AF needed >10 µg/min infusion rate. After isolation of the primary arrhythmogenic PV in 26 out of 115 patients (23%) APCs and AF from other foci were seen only during a mean isoproterenol infusion rate of 15.2 ± 4.2 µg/min (range 10-20 µg/min). These arrhythmogenic APCs originated from the left atrial posterior wall in the proximity of the RUPV in 4 patients, from the SVC in 4 patients and from a different PV in 18 patients.

   The ostial circumference of the PVs was divided into 16 sectors based on the maximum number of electrodes present on the 2-cm loop catheter. The number of sectors showing PVPs on the circular catheter, at which RF energy was delivered to complete ostial isolation, were documented. PVPs were seen and required ablation in all infero-anterior sectors of the RUPV ostia. In the LUPV the superior and inferior segments appeared critical for PV activation in all patients. No sector consistently showed preferential conduction around the circumferences of the distal and ostial LLPVs and RLPVs. No correlation between the distally and ostially ablated sectors was observed. In order to perform ostial isolation ablation of all 16 sectors was needed in 65% of RUPVs, 76% of LUPVs, 45% of LLPVs, and 2% of the RLPVs.

COMPLICATIONS AND FOLLOW-UP
   Pulmonary vein venograms performed immediately after distal ablation lesions showed > 50 % narrowing of the RUPV in one patient, the LUPV in two patients and both LUPV and LLPV in one patient. Narrowing < 25 % in two LUPV, and three RUPV. No further narrowing was seen following ostial isolation. The Spiral-CT scan performed in all patients two months after PV isolation showed thickening of the posterior wall extending to the LUPV and causing moderate to severe stenosis (60-50% narrowing) in 2 asymptomatic patients. Severe stenosis (> 70 % narrowing) of both LUPV and LLPV was seen in another patient. Two of these 3 patients underwent dilatation by balloon angioplasty. One patient undergoing ostial isolation showed a 50-60% ostial narrowing at the two-month follow-up. Anticoagulation therapy was continued in the two patients with > 50% PV narrowing. Another patient developed aphasia documented at the end of the ablation, which nearly resolved after 48 hours.

   During a mean follow-up time of 5.3 ± 1.4 month, AF recurrence was documented in 26 patients (22%). Twenty-four patients experienced recurrence of AF within 2 weeks after ablation and two patients had recurrence after 3 weeks. Five patients presented with firing from the previously isolated PV. The reasons for recurrence were found to be recovery of the PV ostium (2 patients) and a large PV ostium (2 LLPVs and 1 RUPV). These Patients were successfully isolated in a second procedure. Nine of these patients underwent repeat procedure during which recurrence appeared associated with firing from veins not targeted during the first procedure in 5 patients and with firing from a focus in the posterior wall of the left atrium in the vicinity of the RUPV ostium in two patients. 12 patients responded to previously ineffective drug therapy. In one of them, following isolation of three PVs, firing from the posterior wall of the left atrium close to the left PVs was documented during the first procedure and could not be abolished. One patient with recurrence had a large single ostium right PV, which could not be proximally isolated during the initial procedure. Post ablation only 3 of the 115 patients continued to have atrial fibrillation despite drug therapy, and are scheduled for re-ablation.

   In conclusion, the reported recurrence rates of AF after focal ablation have been quite high with the majority of patients requiring 2 or more procedures to achieve cure (16,20,21). In our experience circular mapping guided lesions appeared to provide the highest probability of cure with the first procedure. We documented a 23 % early recurrence rate, associated to 1) an arrhythmogenic PV not seen at the time of the initial ablation, 2) foci originating from the posterior wall of the left atrium in the vicinity of the right upper pulmonary vein, 3) conduction recovery of ablated pulmonary veins. The main advantage of isolation with the ultrasound system was the lack of PV stenosis. Design flaws were responsible for nearly 50% of the recurrences seen after ultrasound ablation, and if properly resolved could improve the cure achieved with this system. Isolation with the CARTO mapping system appeared to result in an unacceptable rate of PV stenosis.

   Circular mapping guided ablation appeared to simplify and facilitate isolation of the pulmonary veins. Although distal isolation can be achieved by limited ablation lesions it appears to have a higher risk of stenosis and it may be effective in only a third of the patients. It appears imperative that an effort is made to deliver lesions only at the ostium to avoid or limit pulmonary vein stenosis, which remains a problem if one applies radiofrequency at the sites where the circular catheter is more stable.

REFERENCES

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2. Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation. 1990;82:1106-16.

3. Moe GK. Evidence for reentry as a mechanism of cardiac arrhythmias. Rev Physiol Biochem Pharmacol. 1975;72:55-81.

4. Moe GK. A conceptual model of atrial fibrillation. J Electrocardiol. 1968;1:145-6.

5. Cox JL, Schuessler RB, Boineau JP. The development of the Maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000;12:2-14.

6. Cox JL, Sundt TM, 3rd. The surgical management of atrial fibrillation. Annu Rev Med. 1997;48:511-23.

7. Jais P, Shah DC, Haissaguerre M, Takahashi A, Lavergne T, Hocini M, Garrigue S, Barold SS, Le Metayer P, Clementy J. Efficacy and safety of septal and left-atrial linear ablation for atrial fibrillation. Am J Cardiol. 1999;84:139R-146R.

8. Haissaguerre M, Jais P, Shah DC, Gencel L, Pradeau V, Garrigues S, Chouairi S, Hocini M, Le Metayer P, Roudaut R, Clementy J. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7:1132-44.

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10. Natale A, Leonelli F, Beheiry S, Newby K, Pisano E, Potenza D, Rajkovich K, Wides B, Cromwell L, Tomassoni G. Catheter ablation approach on the right side only for paroxysmal atrial fibrillation therapy: long-term results. Pacing Clin Electrophysiol. 2000;23:224-33.

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13. Schwartzman D, Kuck KH. Anatomy-guided linear atrial lesions for radiofrequency catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol. 1998;21:1959-78.

14. Garg A, Finneran W, Mollerus M, Birgersdotter-Green U, Fujimura O, Tone L, Feld GK. Right atrial compartmentalization using radiofrequency catheter ablation for management of patients with refractory atrial fibrillation. J Cardiovasc Electrophysiol. 1999;10:763-71.

15. Scherf D. The mechanism of flutter and fibrillation. Am Heart J. 1966;71:273-80.

16. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659-66.

17. Natale A, Pisano E, Beheiry S, Richey M, Leonelli F, Fanelli R, Potenza M, Tomassoni G. Ablation of right and left atrial premature beats following cardioversion in patients with chronic atrial fibrillation refractory to antiarrhythmic drugs. Am J Cardiol. 2000;85:1372-5.

18. Kanagaratnam L TG, Schweikert R ,Pavia P, Bash D, Beheiry S,Lesh M, Niebauer M, Saliba W, Chung M, Tchou P, Natale A. Empirical Pulmonary Vein Isolation in patients with Chronic Atrial Fibrillation Using a Three Dimensional Non-fluoroscopic Mapping System: Long-term follow-up. Pacing and Clinical Electrophysilogy. 2000.

19. Natale A, Pisano E, Shewchik J, Bash D, Fanelli R, Potenza D, Santarelli P, Schweikert R, White R, Saliba W, Kanagaratnam L, Tchou P, Lesh M. First human experience with pulmonary vein isolation using a through- the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation [In Process Citation]. Circulation. 2000;102:1879-82.

20. Chen SA, Hsieh MH, Tai CT, Tsai CF, Prakash VS, Yu WC, Hsu TL, Ding YA, Chang MS. 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.

21. Lin WS, Prakash VS, Tai CT, Hsieh MH, Tsai CF, Yu WC, Lin YK, Ding YA, Chang MS, Chen SA. Pulmonary vein morphology in patients with paroxysmal atrial fibrillation initiated by ectopic beats originating from the pulmonary veins: implications for catheter ablation. Circulation. 2000;101:1274-81

 

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
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Dr. Armando Pacher
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