Chinese Medical Journal 2005;118(14):1150-1155
Impact of different ablation strategies on the delayed cure after trans-catheter ablation for treating patients with atrial fibrillation

DONG Jian-zeng,  LIU Xing-peng,  LONG De-yong,  LIU Xiao-qing,  WANG Jing,  Fang Dong-ping,  HAO Peng,  LI Yong-sheng,  LIU Chuang,  MA Chang-sheng

DONG Jian-zeng (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

LIU Xing-peng (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

LONG De-yong (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

LIU Xiao-qing (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

WANG Jing (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

Fang Dong-ping (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

HAO Peng (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

LI Yong-sheng (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

LIU Chuang (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

MA Chang-sheng (Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China)

Correspondence to:MA Chang-sheng,Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China (Tel: . Fax:. E-mail:chshma@vip.sina.com)
Keywords
atrial fibrillation;catheter ablation;pulmonary vein
Abstract
Background Delayed cure had been observed in recurrent cases after index ablation of atrial fibrillation (AF), however, its mechanism and incidence have not been elucidated in detail. This study aims to investigate the impact of different ablation strategies on the incidence of delayed cure and its possible mechanisms after trans-catheter ablation of AF.
Methods One hundred and fifty-one consecutive cases with highly symptomatic, drug refractory AF were included in this study [M/F=109/42, mean age (56.0±11.2) (18-79) years]. Segmental pulmonary vein ablation (SPVA) was performed in 83 patients with the guidance of circular mapping catheter (SPVA Group), circumferential PV linear ablation (CPVA) was carried out in the rest 68 cases under the guidance of 3 dimensional mapping system in conjunction with circular mapping catheter (CPVA Group). Delayed cure was defined as that early recurrence of atrial tachyarrhythmias (AF, atrial tachycardia, or atrial flutter) after ablation procedure was no longer observed during subsequent follow-up, and stable sinus rhythm was maintained ≥2 months.
Results Early recurrence of atrial tachyarrhythmias was detected in 41 cases from SPVA group and 23 cases from CPVA group, and delayed cure occurred in 21.9% (9/41) of the cases from SPVA group and 47.8% (11/23) of the cases from CPVA group, more delayed cure in later group was observed (P<0.05). Meanwhile, patients in SPVA group took a longer time to achieve a delayed cure [(27.0±18.0) days vs (14.0±8.1) days, P<0.05], and presented more recurrent episodes [(3.50±1.08) times a week vs (2.42±1.11) times a week, P<0.05]. However, recurrent episodes after index ablation were markedly decreased in cases with delayed cure from both groups (P<0.05).
Conclusions Despite of an early recurrence of atrial tachyarrhythimas after index ablation of AF, delayed cure occurs in a significant number of patients undergoing either SPVA or CPVA. However, different ablation strategies place different impact on the delayed cure, more delayed cure is obtained with CPVA approach, and the delayed cure occurs earlier with this approach; the average recurrent episodes before delayed cure are also less frequently detected in CPVA group compared with those in SPVA group.
After initially successful pulmonary vein (PV) isolation in patients with atrial fibrillation (AF), atrial tachyarrythmias recurs in 20% to 50% of patients.[1-4] Despite of early recurrence, some of these patients had experienced a delayed cure during subsequent follow-up. So far, only limited studies concerned with delayed cure have been published,[5,6] meanwhile, in these studies, only segmental pulmonary vein ostium ablation (SPVA) approach was used. With wide application of three-dimension mapping system to facilitate the circumferential pulmonary vein ablation (CPVA), these studies involved only segmental ablation approach can no longer reflect current development. From November 2002 to November 2004, a cohort of 151 consecutive patients with AF had undergone SPVA or CPVA in our lab, and the present paper aims to retrospectively examine these patients and investigate the impact of different ablation strategies on the delayed cure.

METHODS

Patients
To exclude the bias caused by the differences in learning curve, the initial 50 cases underwent SPVA and CPVA approach were not included in this study, and all procedures were performed by operators with the same experience. Finally, 151 consecutive cases [M/F=109/42, mean age (56.0±11.2) (18-79) years] with paroxysmal AF (n=129) or persistent AF (n=14) or permanent AF (n=8) were included in this study, and all patients were highly symptomatic and drug refractory. Mean AF duration was (86.5±83.7) (2-360) months, mean left atrium (LA) size was (37.7±5.7) (28-55) mm, and 34.4% (52/151) of all cases had concomitant hypertension and structural heart disease (SHD), atrial flutter (AFL) was diagnosed in 11.3% (17/151) of all cases. Before the procedure, antiarrhythmic drugs (AAD) except amiodarone were discontinued for at least 5 half lives, and LA thrombus was excluded by transesophageal echo examination 1-3 days before the operation. Written informed consent was obtained from all patients. As shown in Table 1 , 83 cases received SPVA approach with the guiding of circular PV mapping catheter, and 68 cases received CPVA approach under the guiding of three-dimensional (3-D) mapping system in conjunction with single circular PV mapping catheter. More persistent and permanent AF, and less paroxysmal AF were included in CPVA group, and no significant difference was found between other clinical variables.

Mapping and ablation
Coronary sinus catheter was placed via subclavian vein entry. LA and pulmonary veins (PVs) were explored by mapping and ablation catheter via trans-septal approach. In SPVA group, only one trans-septal puncture was carried out, then a left Swartz sheath (St. Jude Medical, USA) and an ablation catheter were placed into LA via the single puncture site, and the circular mapping catheter was placed into LA via the sheath. In CPVA group, two Swartz sheaths were advanced into LA via 2 puncture sites, then a cool saline irrigated catheter (ThermcoolTM, Webster-Biosense, USA) and a circular mapping catheter were introduced into LA via the 2 Swartz sheaths respectively. The sheaths were flushed with continuous injection of saline (20 ml/h) to keep patency. Intra-procedural thromboembolism was prevented by heparin titration to maintain activated clotting time (ACT) between 200-300 seconds. Ablation techniques have been reported in detail in previous study. Briefly, PVs’ angiogram was carried out first, then Haissaguerre approach[1,2,7] was employed to carry out SPVA in SPVA group. While in CPVA group, after angiogram of PVs, LA geometry was reconstructed using 3-D mapping system (CARTO, Webster-Biosense, USA or EnSite/NavX, St. Jude Medical, USA), then the ablation process was navigated via the geometry.[3,4,8] Procedural end-point was electrical isolation of PVs validated by circular mapping catheter.

Post-ablation management
All patients (except contraindications) received one of the AADs during the first month after ablation. From the second month, AAD was discontinued so the procedural outcomes could be accurately evaluated. All patients were placed on anticoagulant treatment with low molecular heparin and wafarin during the first 3 days after ablation, but discharged only on wafarin and international normalization ratio (INR) was maintained between 1.8-2.5. Wafarin was withdrawn 3 months later if no AF was detected, and wafarin was continued for recurrent cases, which had risk factors for thromboembolism.

Post-ablation follow-up
Follow-up consisted of out-patient visit, telephone inquiry, serial ECG, Holter monitoring at 1 week, 2 weeks, and 1, 3, 6 months after ablation. The incidence, duration of recurrent atrial tachyarrhythmias and its response to drug therapy were recorded. The patients lost to follow-up were excluded from this study.

Difinition
Previous study[9] found left atrial tachycardia (AT) or left AFL, even right AFL could be the arrhythmia secondary to LA ablation. Wazni et al[9] and Roithinger et al[10] postulated the anatomic and electrical barriers induced by LA ablation result in the organization of AF, and AT or AFL post ablation is the manifested form of organized AF. Thus any atrial tachyarrhythmia post index ablation was defined as recurrence.

Early recurrence
Any atrial tachyarrhythmias developed within 1 month after ablation.

Late recurrence
No atrial tachyarrhythmias in the first month after ablation, but atrial tachyarrhythmia was observed during subsequent follow-up.

Success
Stable sinus rhythm was maintained without any AADs.

Delayed cure
Despite of early recurrence, AF resolved during subsequent follow-up, and stable sinus rhythm was maintained 2 months without any AADs.

Delayed time
The time from procedure to the last recurrent episodes.

Statistics
Continuous variables were expressed as mean±standard deviation (SD), and compared by t test. Categorical variables were compared by χ2 test. P<0.05 was considered statistically significant.

RESULTS

Follow-up outcomes are shown in Table 2.

Delayed cure
Mean follow-up for patents in SPVA group and CPVA group was (12.7±5.6) (3.5-27.0) months and (7.2±3.7) (3.5-8.0) months respectively. Early recurrence had been detected in 49.4% (41/83)of patients in SPVA group, and 9 of the 41 cases had been confirmed as delayed cure during subsequent follow-up with a delayed cure rate of 21.9% (9/41). Early recurrence had been observed in 33.8% (23/68)of patients who received CPVA approach, and 11 of the 23 cases had been diagnosed as delayed cure with a delayed cure rate of 47.8% (11/23). Delayed cure rate was significantly higher in CPVA group (P<0.05). One late recurrence from CPVA group and the other one from SPVA group were diagnosed 2 months after ablation. After delayed cure, no recurrent episodes were detected during subsequent follow-up. Accumulative success rate was 82.4% (56/68) in CPVA group and 60.2% (50/83) in SPVA group, significantly higher in former group (P<0.05).

Characteristics of delayed cure
Fig. 1 and Fig. 2 illustrate the episodes of atrial tachyarrhythmias before and after procedure in cases with delayed cure. Compared with the average episodes of AF before procedure, there were less recurrent episodes in cases with delayed cure after index ablation. For the 7 cases with delayed cure in CPVA group, only 1-4 episodes were confirmed after ablation. In SPVA group, increased recurrent episodes were detected in only one case. Meanwhile, the patients in SPVA group took a longer time to achieve a delayed cure [(27.0±18.0) days vs (14.0±8.1) days, P<0.05], and recurrent episodes were also more frequently observed [(3.50±1.08) times a week vs (2.42±1.11) times a week, P<0.05] compared with CPVA group. For the 9 cases with delayed cure from SPVA group, recurrent episodes were mainly AF (8/9), and only one case with AFL was detected (1/9), which was converted to sinus rhythm with electrical cardioversion. For cases with delayed cure from CPVA group, recurrent atrial tachyarrhythimias included 6 cases with AF (55%) and 5 cases (45%) with AFL or AT. AFL or AT automatically terminated in one of the 5 cases 2 days after occurrence, and the other 4 cases were converted to sinus rhythm by electrical cardioversion, stable sinus rhythm was maintained in the 5 cases thereafter. Recurrent AFL tended to be higher in CPVA group, but reached no statistical significance.

DISCUSSION

For patients with early recurrence after trans-catheter ablation of AF either early re-ablation or late re-ablation after a period of follow-up was considered as a further treating strategy. With increasing awareness of the delayed cure after trans-catheter ablation in patients with AF, late re-ablation after a period of follow-up was proposed in increasing number of centers to avoid unnecessary repeat procedures and save medical resources. At present, three-month observation after index ablation was proposed as a follow-up strategy in majority of EP centers, but no clinical study supported the concept. Meanwhile, three-month follow-up regardless of individual difference would unnecessarily extend patient’s discomforts if AF remained unaffected after procedure. However, with new ablation strategies emerged in clinical field, to identify the patients who have a high possibility of delayed cure and to define the proper time of follow-up before the second procedure remained a challenge to doctors. Therefore, to investigate the impact of different ablation strategies on the delayed cure will provide important implications for clinical practice.

Present study found majority of cases with delayed cure presented decreased episodes of atrial tachyarrhythmias after index ablation, but there were some differences in recurrent profile between these 2 ablation strategies. More cases with delayed cure and less recurrent episodes in cases with delayed cure were observed in CPVA group. Meanwhile, we found mean follow-up before the delayed cure was 14 days for patients underwent CPVA and 27 days for patients underwent SPVA, a shorter follow-up before the delayed cure was demonstrated in patients underwent CPVA (P<0.05). Thus, for recurrent cases underwent CPVA, at least 2 weeks of follow-up is recommended to determine whether a re-ablation procedure is needed, while for recurrent cases received SPVA, at least 4 weeks is proposed, especially for patients with reduced episodes. In other words, if AF remained unaffected at end of the follow-up time we recommended, and resistant to drug therapy, it is unnecessary to wait for 3 months to decide whether a repeat procedure is needed.

The difference of recurrent atrial tachyarrhythimas between two groups of patients was probably related to the ablation strategies. Theoretically, more PV-LA junction tissue was included by CPVA approach,[11] and the substrate around PV ostia was also more extensively modified. A recent study demonstrated that recurrent AF or AT was closely associated with the discontinuous linear lesion produced around PVs.[12,13] So when a gap along the circumferential linear line existed, the rapid activities originated from PVs would conduct to LA and developed into AFL or AT.[14] If more than one gap existed along the linear lesion, PV’s activities would likely develop into AF because of multiple wave outlets.[15] While SPVA approach aims at the PV ostium to isolate PVs, and LA substrate around PVs was not modified, thus when recovered conduction originated from PV’s activities pass through the LA substrate around PVs, the fibrillatory property of the tissue tends to cause AF.[16]

The delayed cure in this study was mainly found in the patients with paroxysmal AF, and its possible reason was only limited number of patients with persistent AF and permanent AF were included in this study, but it could not exclude some special features associated with these two kinds of persistent AF.

The mechanism responsible for delayed cure remained unclear. We postulated tissue necrosis and inflammatory reaction caused by ablation application could partly explain the underlying mechanism. Generally, these changes take approximately 2 weeks to resolve.[17] On the other hand, electrical remolding of LA does take times to return to normal after LA substrate was modified.[17] Less recurrent episodes for patients with delayed cure also suggested a residual effect of ablation on myocardium. AF exacerbated in one recurrent case from SPVA group suggested that an incomplete lesion on the foci might have increased the arrhythmogenicity of LA tissue.

This study is limited by its retrospective nature and relatively small group of patients included, and inherent limitation of follow-up could make an error explanation. Also, the difference in AF burden may have led to different outcomes. Despite of these possible limitations, present study demonstrated a special trend that can be further studied in a larger cohort of patients.

In summary, present study indicates that a delayed cure can occur in a significant number of patients despite of an early recurrence of atrial tachyarrhythimas after trans-catheter ablation of AF. More delayed cure could be obtained with CPVA approach. Two weeks of follow-up for CPVA approach and 4 weeks for SPVA approach are recommended as the follow-up strategy.

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  1. China “Tenth Five” Research Project,No. 2004BA714B04;