Intracardiac Echocardiography guided Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation: Impact on Outcome and Complications

Sherif H. Zaky MD, Mostafa Alrefaee MD, Salah Atta MD, Hesham Hegazy MD, Jehan Abd Alhalim,MD, Laila Al-Hoty, NSc, Mahmood S Nsc.

From Babtain Cardiac Center, Dammam , Saudi Arabia Background: Pulmonary (PV) antrum ablation is considered the proper modality for electrical isolation of PV (PVI) and treatment of drug refractory paroxysmal atrial fibrillation (PAF). Conventional PVI using fluoroscopy alone can not guarantee neither the exact antral site of ablation nor the limit for radiofrequency power titration . The objective of this study was to assess the role of intracardiac echocardiography (ICE) for visualization & proper ablation of the PV antrum and its effect on both short-term success and incidence of complications in patients undergoing PVI for treatment of PAF. Patients and Methods: Thirty one patients (21 males, mean age 41.3+5.1 ys.) underwent PVI for treatment of PAF. Each patient underwent antral isolation of all PVs using an 8mm tip or irrigated tip ablation catheters. PVI was performed using electrophysiologic circular mapping (CM) alone (group1, 14 patients), CM and ICE (group 2, 17 patients) with titration of radiofrequency energy based on visualization of microbubble by ICE in case of group 2 or impedance rise in case of groop1. Pulsed wave Doppler was done before and after ablation of PVs in group 2 patients to assess for PV stenosis. Results: There was a significant difference between both groups in terms of mean fluoroscopy time (85 + 32 in group 1 vs. 61 + 44 min. in group 2, p< 0.05) and mean number of RF lesions per vein for complete isolation (15.5 + 2 vs. 8.5 + 2, P< 0.05) respectively. After a mean follow-up time of 12.5 + 2.3 months, 35% (5/14) of patients in groups 1, and 17.5% (3/17) experienced recurrence of AF, respectively (P< 0.05). Moreover, no one in group 2 patients experienced severe (>70%) PV stenosis postoperatively. Whereas, severe PV stenosis with dyspnea was documented in 3 out of 14 (3.5%) patients in group 1. No embolic events occurred in either groups. Conclusion: Use of ICE improves the outcome of PVI, reduces both fluoroscopy time and number of lesions per pulmonary vein. Power adjustment guided by direct visualization of microbubble formation reduces the lesions sufficient for complete PVI and thus risk of PV stenosis and improves short term cure. Key words : atrial fibrillation ablation pulmonary vein isolation - intracardiac echo (ICE).

Introduction
Radiofrequency (RF) catheter ablation has become first-line therapy for patients with drug-refractory atrial fibrillation (AF).(1,2) An early ablation strategy consisted of focal ablation of triggers inside the pulmonary veins (PVs) (3). To prevent complications of PV

stenosis, this method was modified to electrical isolation of the PV by segmental isolation at the ostium.(4,5) Strategies evolved to include wide area encircling of the PV antrum using sophisticated three-dimensional mapping systems that could reconstruct atrial anatomy for guiding ablation and limiting fluoroscopy time.(6,7) Phased-array intracardiac echocardiography has been shown to be helpful in defining right and left atrial structures most importantly the exact antrum of pulmonary veins. (8). In interventional electrophysiology procedures, effective ablation of cardiac tissue is dependent on the extent of contact between the ablation catheter tip and the endocardial surface.(9). We hypothesized that intracardiac echocardiography (ICE) would improve the success rates and minimize complications associated with PV isolation procedures by allowing real-time monitoring of both PV ostium and radiofrequency (RF) energy delivery. The purpose of this study was to compare the efficacy and safety of PV isolation using circular mapping alone versus circular mapping with intracardiac echo (ICE) guidance in patients with paroxysmal AF and to assess the utility of ICE-detected microbubbles as a guide to RF titration.

Methods
Patients

Between December 2006 and june 2008, 31 consecutive patients were referred to our laboratory for ablation of AF. All patients signed a written informed consent . Antiarrhythmic drugs were discontinued at least 5 half-lives before the ablation procedure. Immediately before the procedure, transesophageal echocardiography was performed in all study patients to rule out any left atrial masses. Paroxysmal AF was defined as self-terminating episodes lasting < 7 days. We excluded Persistent AF which was considered when AF episodes lasted longer than 7 days and when pharmacological or DC cardioversion was needed to restore sinus rhythm and permanent AF defined as episodes failing cardioversion (1) Anaethesia workup : All patients were fasting before procedure, transcutaneous cardioversion/defiberllation pads placed prior to induction. All patients were monitored by12 leads ECG , invasive, arterial blood pressure and pulse oximeter monitoring .All patients but 8 (4 in each group) received propofol/fentanyl induction of general anesthesia with laryngeal mask airway and spontaneous breathing of 60% oxygen in air supplemented with sevoflurane inhalation to deepen the anesthesia. In 8 patients laryngeal mask airway was not tolerated and required endotracheal intubation, muscle relaxation using atracurium and were mechanically ventilated , all patients were safely extubated and stayed under full monitored observation in the recovery area for at least one hour before shifting to the cardiac wards. Circular MappingGuided PV Isolation In all patients of both groups a decapolar coronary sinus catheter was inserted via right femoral sheath. The left atrium was instrumented using an 8 F sheath (Swartz SR0,

St.Jude) via Rt.femoral vein via a trans-septal puncture if no patent foramen oval was found. Pulmonary vein ostia were localized by performing PV angiogram. All pulmonary veins were canulated with the sheath or an inner 6 F NIH catheter where PV angiography during adenosine-induced (range, 12 to 24 mg) asystole was performed. The PV angiogram was obtained in both 45-degree left anterior oblique and 30-degree right anterior oblique views (LAO). Twenty to 25 mL of manually injected contrast was used for each angiogram. A guide wire (0.035) was then advanced to the left atrium through the trans-septal sheath then sheath withdrawn to Rt.atrium. An ablation catheter was passed through a third sheath in Rt.femoral vein. The ablation catheter was advanced to the left atrium through same transeptal puncture guided by the wire and fluoroscopy in LAO view. The sheath was advanced to the left atrium again and wire replaced by a deflectable 3uperior3 circumferential catheter (LASSO) with deflectable ring diameter ranging from 15 to 25 mm. The Lasso catheter was positioned at the pulmonary vein ostia under fluoroscopy guidance only in group 1 patients. Electrical mapping of PV and left atrial potentials was used to apply proximal lesions guided by PV potentials proximally recorded by Lasso catheter in the antrum of PV as defined by angiogram (At junction with appendage edge in case of left PVs, or lateral border of ineratrial septum in case of right PVs.). Intracardiac Echocardiogram and Circular MappingGuided PV Isolation In group 2 patients (17 patients), a 9 F, deflectable, 64 element phased-array ultrasound imaging ICEcatheter ( (ViewFlex, EP-med systems, New Jersy) was introduced through a 10-Fr sheath via the left femoral vein additional to the previously described three catheters. The ICE catheter with bidrodirectional tip deflectability was introducedand, fluoroscopically positioned in the right atrium. The ICE catheter was connected to an ultrasound platform (Viewmate system). The electrophysiologist performing the mapping and ablation procedure optimized the ICE images. The trans-septal puncture was performed under ICE guidance to visualize the intra-atrial septum in group 2 patients. All PV ostia were defined after transseptal puncture . Pulsed-wave 3uperio flow velocities of all PVs were recorded before and after ablation to assess PV narrowing, and ablation at the PV ostium was aborted when the PV diastolic flow velocity exceeded 1.5 m/sec.. In group 2 patients, RF energy was delivered using the same ablation catheters applying the ablation protocol described above for group 1 patients.
Microbubbles Monitoring With Intracardiac Echocardiogram

In group 2, ICE was used not only to ensure circular mapping catheter positioning (Figure 1) and appropriate site of energy delivery but also to guide energy titration by monitoring microbubble formation. Two types of bubble patterns were seen with ICE: (1) scattered microbubble (type 1), reflecting early tissue overheating (Figure 2); and (2) brisk shower of dense microbubbles (type 2), reflecting impending impedance rise (Figure 3).

Protocol of RF ablation. Ablation catheters used were either 8 mm Tip , (Blazer, EP Technologies) or Irrigated tip 4 mm thermocool catheter, (Bisense Webster ). A 35C target temperature was chosen for RF energy delivery through the cooled-tip catheter. A 50C was set as target in case of 8 mm tip catheters and in both a Stockert RF generator (Biosense Webster) was used. Although we applied the same energy delivery protocol for group 1 and 2 patients, power was titrated upward (5-watt increments), watching for formation of type 1 bubbles only in the latter group while watching for impedance rise only in group 1. When the type 1 microbubble pattern was seen, energy was titrated down by 5-watt decrements until microbubble generation subsided. Energy delivery was terminated when type 2 bubbles were seen. Definition of Successful PV Isolation PV isolation was considered acutely successful after abolition of all ostial PV potentials recorded on the circular mapping catheter during sinus rhythm or coronary sinus and right atrial pacing

LSP Fig. 1 Circular mapping catheter (Lasso) positioned at the ostium of the left superior
(pulmonary vein (LSPV

Fig.2 Type 2 ( Localized) microbubbles during ablation at the ostium of the right 4superior PV
(RSPV). The Lasso catheter (arrows) is placed at the ostium of the vein

Fig.3 Shower of dense microbubbles (type 2 bubbles) extending to the left atrial cavity observed
during radiofrequency delivery at the ostium of the right superior pulmonary vein (RSPV).

Fig.4 Transeptal puncture under ICE guidance.( arrow at needle tip puncturing the inter atrial septum) LA: left atrium, RA right atrium.

During the procedure, systemic anticoagulation was achieved with intravenous heparin for all patients. After a loading dose of 100 U/kg, a standard heparin infusion of 10 U/kg/hour was initiated. Activated clotting times (ACT) was checked at 10- to 15-minute intervals until therapeutic anticoagulation is achieved and then at 30 minute intervals during the case. The lower level of anticoagulation should be maintained at an ACT of at least 250350 seconds throughout the procedure.
Statistical Analysis

Continuous variables are expressed as meanSD. Continuous variables were compared by Students t test. Differences among groups of continuous variables were determined by ANOVA. Categorical variables were compared by X2 analysis or with Fishers exact test. Follow-Up Patients were discharged home the day after ablation. All patients were discharged on oral anticoagulation with warfarin (keeping INR at range 2.5-3.0) and one antiarrhythmic drug (either propaphenone or Amiodarone) for three months. Patients were also monitored with Holter recording before discharge and at 3- and 6-month follow-up. Follow-up was scheduled at 1, 3, 6, and 12 months after ablation. After 3 months, anticoagulation and antiarrhythmic drug was stopped unless patients experienced recurrence of AF. For analysis, recurrence of AF was defined as AF occurring 8 or more weeks after the procedure. Table 1 Patients' Demographics

Group 1 (Without ICE) (No. patients (male/female (.Age (ys

Group 2 ((With ICE

11/4 2.3 + 43.1 1.8 + 2.6 2/14

10/7 1.9 + 40.7 1.2 + 3.1 3/17

Duration of AF, y SHD

LA size, cm

0.6 + 4.2 11 + 53

0.5 + 4.3 7 + 54
SHD : structural heart disease LA : left atrium

,Ejection fraction ,%

Results : Thirty one consecutive patients were referred to our laboratory for ablation of symptomatic paroxysmal AF (21 males, mean age 41.3+5.1 ys.).Structural heart disease was present in 5 patiens (16%). The demographics of the study population are given in Table 1. There was no significant difference between both groups as regards age, gender, duration of AF, LA size, use of AAD, or presence of Structural heart disease Pulmonary vein isolation : A total of 112 PVs in 31 patients were mapped and successfully isolated. A common PV ostium was found in 6 cases ( 3 pts on the right PVs (10.5%) and in 10.5% of the left PVs (3 of 31). A mean of 10.5 + 2 RF lesions (range 6 21 lesions) per PV were delivered to achieve complete isolation. In group 1 pts a mean of 15.5 + 2 lesions per vein were given. Table 2 depicts the acute results in both groups. It was evident that there was a significant difference in terms of fluoroscopy time (85 + 32min. in group 1 Vs. 61 + 44 min. in group2, p<0.05) . The mean number of RF lesions per vein was higher in group 1 patients (15.5 + 2 ) versus 8.5 + 2 lesions per vein in group 2 patients ( P< 0.05). Where procedure time was lower ( but not statistically significant) in group 2 (198 + 72 min.) Vs 261 + 54 min. in group 1 , complications tended to be also lower with group 2 patients : ICE-Guided Ablation Monitoring : Type 1 bubbles were observed during all procedures of group 2 patients in 75% of the lesions delivered during PV isolation and led adjustment of RF power. On the other hand power titration for group 1 patients based on impedance rise was done for PV isolation in 88 % of lesions in group 1 patients. Type 2 bubbles were observed during 43% of lesions delivered in group 2 .Type 2 bubbles preceded impedance rise by a mean of 3.4 seconds (range, 3 to 5) and was always followed by a rise in impedance unless the power was turned off.

Recurrence : As in Table 2 which demonstrates follow-up results, after a mean follow up period of 12.6 + 0.5 months , 8 out of the 31 studied patients ( 26%) experienced recurrence . The recurrence rate was higher in group 1 patients , 5 out of 14 ( 35%) in comparison to 3 out of 17 in ICE guided ablation group 2 (17.5%) ( P < 0.05). Complications included : one case with tamponade (group 1), 4 had significant PVstenosis (> 70%) detected by angiography at end of procedure (3 in group1). PV stenosis tended to be higher in group 1 than group 2 although not statistically significant.

RSPV

A B (Fig. 5 Pulmonary vein angiography ( RSPV) before ( A) and at end of procedure(B

TABLE 2. Pulmonary Vein Isolation and Follow-Up Results

Group 1 (Without ICE)

Group 2 (With ICE)

No.= 14
No. isolated PVs,
(LSPV/LIPV/RSPV/RIPV)

No.= 17
63 (17/15/17/14) 0.4 + 1.9 72 + 198 44 + 61
2 + 8.5

.P

49 (14/11/14/10) 0.5 + 1.8 261 + 54 32 + 85

15.5 + 2

NS NS NS 0.05 > 0.05 > NS

AAD Procedure time, min Fluoroscopy time, min Mean No. RF lesions/PV Follow-up, months

4 + 13

5 + 10

Recurrence of AF

(35%) 5/14 (28%) 4/14

(17.5%) 3/17 (11.5%) 2/17

0.05 > NS

Complications

ICE indicates intracardiac echo; PV, pulmonary veins; RSPV, right superior pulmonary vein; RIPV, right inferior pulmonary vein; LSPV, left superior pulmonary vein; LIPV, left inferior pulmonary vein; LA, left atrium; and AAD, antiarrhythmic drug

Fig.6 Termination of an AF paroxysm during RF ablation of right superior pulmonary .(vein(RSPV

C Fig. 7 Left superior pulmonary vein (lspv) isolation. A) before isolation under coronary sinus pacing B) start of conduction block between atrial and PV potentials C) after .complete isolation note disappearance of PV potentials

Discussion Our study despite limited number of patients, proves that ICE-guided pulmonary vein isolation is more effective than angiography-guided circular mapping. In addition, monitoring of energy delivery using ICE additionally improved long-term success and was associated with decreased risk of complications. Circular mappingguided PV isolation for treatment of AF has been reported to be effective and feasible.(10,11). The superiority of ICE-guided PV isolation compared with angiography-guided isolation using circular mapping could be explained by 2 factors. First, it appeared that angiography-based placement of the circular mapping catheter is less accurate than ICE-assisted positioning. True ostial PV isolation requires abolition of all PV potentials that extend to the PV antrum proximal to the tube-like portion of the vein. Electrical mapping of the sleeves using the circular catheter and direct visualization of the PV ostium (Figure 1) were enhanced by ICE. Second, the poor contact between the ablation catheter tip and the endocardial surface reduces heat transfer to the tissue and allows convective heat loss into the circulating blood.(12,13). Diminished heat delivery to the PV ostial tissue may result in increased power output, inefficient lesion formation, and increased risk of coagulum formation. Kalman et al (14) reported that less than 50% of fluoroscopically guided RF lesions were delivered with good perpendicular contact. Ensuring stability and proper ablation catheter tip tissue contact using ICE might have played an important role in the cure of AF and in the development of severe PV stenosis in our study patients. Mangrum et al(15) reported their experience using radial cross-sectional intracardiac echocardiography to guide anatomically based ostial PV isolation and reported a recurrence rate of 36% after 13+7 months of follow-up in patients with paroxysmal AF. In our study population, all PVs were isolated, whereas Mangrum et al isolated only PVs triggering APCs and AF during the procedur, this might explain our higher success rate in group 2 patients (17.5 %recurrence) in a comparable period of follow up.

Monitoring of Energy Delivery : Radiofrequency energy is conventionally delivered using temperature, power, and impedance monitoring. Energy delivery is typically terminated after approaching programmed ablation time or after a sudden increase in impedance that suggests excessive tissue heating. Increase in impedance has been associated with increased risk of coagulum formation (12) and could be a sign of improper lesion formation, which could create the milieu for PV stenosis. In an experimental model, Kalman et al (14) reported that showers of microbubbles and occasionally of coagulum preceded rises in impedance. These findings occurred with higher frequency when the electrode-tissue contact was suboptimal. In the present study, we noticed microbubbles in 75% of lesions in group 2 patients coinciding with less pulses needed for complete isolation of pulmonary veins, hence presumably better and effective lesions. Using microbubble generation to guide energy delivery may optimize lesion formation ensuring effective energy delivery and avoiding tissues overheating. In addition, conventional RF energy delivery using a cooled-tip catheter is generally limited to a target temperature of 35C. By using the ICE-guided microbubble monitoring strategy, we increased the power based on objective findings. Of interest, prevention of a dense shower of microbubbles with ICE imaging also seemed to diminish the risk of embolic events in our patient population. Study Limitations The limited number of patients and lack of random assignment to treatment groups could have affected our findings. However, given the similarity among the treatment groups in baseline characteristics, we feel this is unlikely. We had acquired an increased experience that may have resulted in improved technical expertise at performing circular mapping and ablation. On the other hand, the first 14 patients undergoing circular mappingguided isolation alone were among the learning curve and could have affected the outcomes reported. Conclusions This study has compared ICE-guided PV isolation to circular mappingguided PV isolation in patients with AF. ICE-guided PV isolation seems to be was more effective than conventional circular mappingguided PV isolation in patients with AF with better initial outcome and less rate of recurrence. In addition to improved short term success rates, monitoring of microbubble formation using ICE during radiofrequency energy delivery decreased rate of complications namely thromboembolism and PV stenosis. References 1.Fisher JD, Spinelli MA, Mookherjee D, et al. Atrial fibrillation ablation: reaching the mainstream. Pacing Clin Electrophysiol. 2006;29:523537. 2. Cappato R, Calkins H, Chen SA, et al. Worldwide survey on the methods, efficacy and safety of catheter ablation for human atrial fibrillation. Circulation. 2005;111:11001105. . 3. 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;339:659666. . 4. Robbins IM, Colvin EV, Doyle TP, et al. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation. 1998;98:17691775.

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