ABSTRACT Oral Presentation Academic research paper on "Clinical medicine"

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Feasibility and clinical usefulness of high resolution sound map with cross plane method for AF ablation

YH Chun, D Sato, H Kitajima, YNishikawa, H Mani

Koseikai Takeda Hospital, Japan

High resolution soundmap, constructed with multiple ultrasound fans collected from both right and left atrium as a real time visualization of LA was invented and assessed its feasibility and clinical usefulness for atrial fibrillation (AF) ablation.

Methods: Fifty-two patients were included this study. High resolution soundmap was obtained using an intracardiac echo catheter equipped with a magnetic sensor for electroanatomical mapping function of CARTO3 by reconstruction of multiple two dimensional ultrasound fans to a three-dimensional left atrial image. In this study intracardiac echo catheter was navigated to the left atrium to get a clear echo closer to the left pulmonary vein, left atrial appendage and antrum of left pulmonary vein.

The ablation procedure was performed to isolate the pulmonary veins circumferentially with high resolution soundmap

Results: The time to create the sound map ranged five to nine min (mean 7.2 +/- 2.8) from the RA andten to twenty (mean 16.5 +/- 3.6) from the LA.

The procedure time range 34 to 67 min (mean 50.2 +/- 16.4). Mean Fluoroscopic time was 42 +/-19 min.

Conclusion: There was no excessive time consumption for making high resolution soundmap in this study. Circumferential pulmonary vein isolation was safely and successfully performed without image integration ofa pre-made three dimensional LA model.

We would conclude that high resolution soundmap is useful for AF ablation and this method will provide the chance to get this curative ablation therapy for the patients without angiogram, or pre made CT image.

Robotic navigation for catheter ablation of atrial fibrillation - is there a learning curve?

Fahd K. Chahadi, Cameron B. Singleton, John Bowyer, Andrew D. McGavigan1'2

Department of Cardiovascular Medicine, Flinders Medical Centre; Faculty of Medicine, Flinders University, Adelaide, Australia

Introduction: There are reports of a significant learning curve for ablation using Robotic Navigation including increased risk of peri-procedural complications. We report our initial experience ofatrial fibrillation ablation with the Hansen Sensei Robotic System.

Methods: Procedural details on 146 consecutive cases using the Hansen system were collated with endpoints of acute procedural success in achieving pulmonary vein isolation or block across linear lesions. Data on procedural time, fluoroscopy time (total and physician-exposed) and complication rate were also collected. Data compared for first and last 50 cases to assess for presence of a learning curve.

Results: Venous isolation achieved in 99%, block across linear lesions in 95%. Complications at 30 days occurred in 5 (3.4%) 4 tamponade and one venous access problem. Late PV stenosis in 3 patients, giving total complication rate of 5.5%. Mean procedural time was 191 mins (110-360), mean total fluoroscopy time 47.9 mins (17 102), mean physician-exposed fluoroscopy 31.9 mins (11-91). Comparing the first and last 50 cases, mean procedural time was 216 vs. 160 mins, total fluoroscopy 52 vs. 43 mins and physician exposed 33.2 vs. 28.3 mins (all p<0.05). Complications occurred in 4 ofthe first 50 and 2 ofthe last 50 (p=NS).

Conclusions: High acute procedural success can be achieved by remote navigation using the Hansen system with a complication rate comparable to published literature. Our data supports the existence of a learning curve for robotic ablation with respect to procedural efficiency and fluoroscopy times, but not with respect to safety.

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Effect of atrial fibrillation on catheter-tissue contact during antral pulmonary vein isolation in humans: lower contact force at the left anterior pulmonary vein in atrial fibrillation compared to sinus or paced rhythm

Saurabh Kumar1,2, Joseph B. Morton1:2, Justin M.S. Lee1, Michael C.G. Wong1'2, Karen HaUoran, Steven J. Spence, Peter M. Kistler1, Jonathan M. Kalman ,

Department of Cardiology; Department of Medicine, The Royal Melbourne Hospital & University of Melbourne, Victoria; Department of Cardiology, Alfred Hospital & Baker IDI, Melbourne, Australia

Background & Objectives: Constant electrode-tissue contact force (CF) is critical for effective lesion creation. It is unknown if atrial rhythm influences CF. We examined the effect of atrial fibrillation (AF) cf. to sinus/paced atrial rhythm on CF during pulmonary vein isolation (PVI).

Methods: 1072 lesions (>20 seconds duration) in 24 patients undergoing PVI facilitated by a novel CF-sensing catheter were assessed for average CF (grams, g), force-time integral (FTI in grams*seconds, g*s) and atrial rhythm during lesion delivery. Operators were blinded to CF data. Atrial rhythm was classified as organized (sinus/atrial paced rhythm at 800 ms) or AF. The left and right PV antra were divided into inferior, superior, carina, posterior and anterior PVs for region specific analyses.

Results: Overall, there were no differences in average CF or FTI in organized rhythm vs. AF (22 ± 14g vs. 22 ±13 g, P=.8; FTI 627 ± 48 g*s vs. 633 ± 393 g*s, P=.5). There were no region specific differences in average CF or FTI in organized rhythm vs. AF, except for the left anterior PVs where average CF and FTI were lower (P=.03 & P=.06 respectively) in AF compared to organized rhythm.

Conclusion: Atrial rhythm influences catheter-tissue contact at the PV antra in a region-specific manner. Whilst AF was associated with similar CF at most antral PV sites, poorer contact was noted at the left anterior PVs which is known to be an important site for PV reconnection. This information has critical implications for ablation efficacy and outcomes during PVI.

First human validation of a new epicardial access needle with a real time pressure monitoring to facilitate epicardial access

Luigi Di Biase, Zoltan Csanadi, Gabor Sandorfi, Edina NagyiBalo, Chintan Trivedi, Andrei Leny, Alexandra Kiss, Andrea Natale, John Burkhardt

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, TX; Department oof Cardiology, University of Debrecen, Debrecen, Hungary

Introduction: Epicardial (epi) ablation represents an adjunctive strategy for the treatment of challenging arrhythmias. Major complications may occur during epi access since the needle may inadvertently puncture the right ventricle (RV), the pleural space or the lung. We sought to evaluate if a new access epi needle reduce the risk for RV puncture and complications.

Methods: 7 consecutive pts with epi arrhythmias (6 ventricular, 1 supraventricular) were enrolled. Epi access with a &ldquo;novel needle&rdquo; embedded with a tip sensor able to record beat-to-beat pressure waveform was utilized. Successful epi access was confirmed by fluoroscopy, contrast injection and visualization ofthe guidewire looping around the epi border ofthe heart. In 4 cases the epi access was obtained by an expert operator, while in 3 cases the access was obtained by a less experienced operator.

Results: Successful epi access was obtained in all cases. No acute and delayed complications occurred. Mean Pericardial pressure/pulsation was 3.5 ±1.3 mmHg while mean RV pressure was 15±4 mmHg (p=0.001). Pressure monitoring identified pericardial wire access position in 75% of the attempts and was able to identify RV puncture in 100% ofthe cases. 3 false negative readings were recorded, where the guidewire was within the pericardial space while the needle tip pressure was indicating differently. Unintended RV puncture occurred in 50% of the cases(always detected). Unintended RV puncture occurred more often in the less experienced operator (6 times vs 2 times, P< 0.05).

Conclusion: Real time pressure monitoring identifies successful pericardial access and RV perforation. This information would be important to facilitate epi access to less experienced operators.

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Endoscopic ablation by unilateral approach (left chest) for lone atrial fibrillation: a single center experience in 100 consecutive patients

Ju Mei, Nan Ma, Fangbao Ding, Yin Chen, Zhaolei Jiang, Fengqing Hu, Haibo Xiao

Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong

University, Shanghai (200092), PR.China

Objective: We presented the technique of our endoscopic ablation by unilateral approach (left chest) andthe follow-up results of 100 patients with lone atrial fibrillation

Methods: Between October 2010 and September 2012, 100 patients with lone atrial fibrillation underwentthis procedure. Among them, 58 were with paroxysmal, 32 were with persistent, and 10 were with long-standing atrial fibrillation. These patients were aged between 30 and 81 including 58 males and 42 females. The procedure was performed on the beating heart, through three ports on left chest wall. Pulmonary vein isolation and ablation ofthe left atrium was achieved by bipolar radiofrequency ablation. Ganglionic plexus ablation was made by the ablation pen. Left atrial appendage was excluded.

Results: Durations of their procedures were 118.3±37.3 mins. No conversion to sternotomy. All patients discharged after 7.5 ±3.2 days and 95 patients maintained sinus rhythm. The mean follow-up duration were 8.9±4.7months. 92(92%) of all patients were in sinus rhythm. 8 patients could not maintain sinus rhythm. Thrombus in the left atrium and stenosis of pulmonary vein were not found after their procedures.

Conclusions: Our endoscopic ablation by unilateral approach ( left chest) for lone atrial fibrillation was safe and effective, so it deserves to be promoted for the treatment of lone atrial fibrillation.

Exploring the relationship between contact force and clinical outcomes between human and robot-assisted AF ablation: early results of MAST-AF

Chu GS1 Chin SH1 Winter J1, Armstrong S 4, Masca N 2, Almeida TP 3 Brown PD1 Schlindwein FS 3 Ng GA1

department of Cardiovascular Sciences, University of Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK Department of Engineering, University of Leicester, UK

Department of Cardiology, University Hospitals of Leicester, Glenfield Hospital, UK

Background & Objectives: Robotic AF ablation may be safer for operators and more efficacious for patients. We aimed tocompare clinical outcomes and contact force between conventional Manual vs. Amigo robotically-assistedAF ablation.

Method: Our UK tertiary centre is pioneering a prospective randomized trial (NCT01583855) comparing Manual versus robotic control with the Amigo Remote Catheter System (Catheter Roboticslnc.), both using the SmartTouch force-sensing catheter and Carto 3 (Biosense Webster), in AF ablation (MAST-AF trial). Left and Right WACA were performed whilst blinded to force data, with electrical PV isolation at30 min as the endpoint.

WACA force data was grouped by region using a clock face model (fig. 1) and analysed retrospectively by a separate physician blinded to the trial arm. A mixed-model ANOVA was fitted to log-transformed data, using planned contrasts to compare the groups. Clinical data was compared using 2-sample t-tests.

Results: Both arms show similar initial results (Table 1). Each had 1 minor vascular complication (not requiring intervention). Atypical flutter was seen in 1 patient in the manual arm 6.7 months post-ablation. 3329 ablation points were analysed, totalling 662,471 force data elements. A trend towards higher force values was observed anterior to the RPV ostia (RWACA 1-5, fig. 2), particularly for Amigo cases.

Conclusion: Our initial data indicates similar clinical outcomes with robotic and human ablation. Catheter force values are higher anterior to the RPV ostia, and is amplified by Amigo assistance. Completion ofrecruitment and one year follow-up is awaited.

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Effect of respiration on catheter movement and stability during cavotricuspid isthmus ablation for atrial flutter

Saurabh Kumar1,2, Joseph B. Mortonl'2, Justin M.S. Lee,, Michael C.G. Wong1*2, Karen Halloran, Steven J. Spence1, Peter M. Kistter1-, Jonathan M. Kalman

Department of Cardiology; Department of Medicine, The Royal Melbourne Hospital & University of Melbourne, Victoria; Department of Cardiology, Alfred Hospital & Baker IDI, Melbourne, Australia

Background & Objectives: Catheter stability is critical in delivering effective radiofrequency energy lesions. We prospectively compared the extent of catheter movement in respiration vs. apnea during cavotricuspid isthmus (CTI) ablation for atrial flutter.

Methods: Thirteen patients underwent ablation under general anesthesia with point-by-point lesions delivered during normal respiration (30 s) alternating with lesions under apnea (30 s) in an anatomically identical location on the CTI. Catheter movement was measured using the EnSite NavX system. CTI was divided into the annular, mid and caval segments. The operators were blinded to the mapping system.

Results: Catheter movement was significantly less during apnea vs. respiration in all CTI segments (p<0.05, Table).

Respiration Apnea P value

Range ofmovement, mean, SD, mm

Annular 6.8 ± 4.7 4.8 ± 2 .025

Mid 6.8 ± 3.9 4 ± 2.2 <.001

Caval 7±5.6 3.5 ± 2.3 <.001

Coefficient ofvariation ofmovement, mean, SD, %

Annular 0.28 ± 0.21 0.19 ± 0.11 .04

Mid 0.28 ±0.16 0.15 ± 0.09 <.001

Caval 0.26± 0.3 0.12 ± 0.09 <.001

Conclusions: Respiration is associated with significantly less catheter stability than apnea during CTI ablation. Greater catheter stability offered by short periods of apnea may improve ablation efficacy during cases with complex CTI anatomy or significant atrial pathology.

Electroanatomic characterization and ablation outcome of nonlesion related left atrial macroreentrant tachycardiain patients without obvious structural heart disease

Jinlin ZHANG

Wuhan Asian Heart Hospital, China

Introduction: Descriptions for left atrial macroreentry tachycardia (LAMRT) in patients without obvious structural heart disease or previous surgery or catheter radiofrequency (RF) ablation have been sparse.

Methods & Results: Ten of 226 patients (7 women, mean age 57 ±14) with LAMRT underwent electroanatomic mapping and catheter ablation. None ofthe 10 patients had structural heart disease or history of previous surgery or catheter ablation. In all patients, the reentry circuits were located within a large low-voltage (bipolar voltage< 0.5 mV) area in left atrium (LA), which contained 2.6±1.2 electrically silent areas (ESAs) and/or lines of double potentials (LDPs). The tachycardia circuit propagated through a narrow isthmus (<5 mm width) bounded by ESAs/LDPs and adjacent anatomical barriers (e.g., mitral annulus). In these isthmus, low amplitude (0.21± 0.05mV), long-duration (123±14ms) fractionated electrograms were found in 8 tachycardias, accounting for 43±5% ofthe tachycardia cycle length.In 2 other tachycardias without fractionated electrograms, the electrogram amplitude in the isthmus was extremely low <0.1 mV). RF energy was delivered at the isthmuses and terminated all 10 tachycardias.

After ablation, the original LAMRT was not inducible in all patients. During follow-up (mean14±10months), 2 patients developed recurrence of ATs and were successfully ablated.

Conclusion: Extensive scarring of the LA formed arrhythmogenic substrates of LAMRT in this group of patients. Ablation targeting these narrow, slow conduction zones eliminated atrial tachycardia in all patients.

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Characteristics of atrial flutter in children and young adults

Yuriko Abe, Naokata Sumitomo, Masataka Kato, Hiromi Okuma, Takahiro Nakamura, Junji Fukuhara, Rie Ichikawa, Masaharu Matsumura, Hiroshi Kamiyama, Mamoru Ayusawa

Nihon University School of Medicine, Japan

Background & Objective: Atrial flutter (AFL) is relatively rare arrhythmia in children, but may cause sudden cardiac death or syncope. This study was aimed to investigate the underlying disease and therapeutic effect of the patients with AFL in children and young adults who had performed an electrophysiological study (EPS) and catheter ablation (RF).

Methods: Twenty three patients (17 male and 6 female) aged 14.7±8.9 (1-34 years old) with AFL were enrolled in this study. The incidence of congenital heart disease, types of operations, associated other arrhythmias, and types of AFL were investigated.

Results: The incidence of congenital heart disease was in 14 cases (61%) including 13 cases of post operation. The incidence of other arrhythmia was in 15 cases (65%); atrial tachycardia (AT) in 8 cases (35%), sick sinus syndrome in 5 cases (22%), atrial fibrillation in 3 cases (13%), complete AV block in 2 cases (9%), and ventricular fibrillation in 1 case (4%). In this study, 5 cases (21%) of AFL were recorded following pacemaker or ICD implantation. The identifiedtypes of AFL were common AFL in 16 cases (70%) and uncommon AFL in 4 cases (17%). After RF, the recurrence rate of AFL was noted in 2 cases (8.7%), AFL and AT in 3 cases (13%), and AT in 1 case (4%).

Conclusion: AFL in children and young adults was commonly associated in patients with postoperative congenital heart disease. In patients with AT and patients after device implantation, AFL was more commonly associated than we expected.

Predictors of development of atrial fibrillation on long-term follow up in patients with macro re-entrant tachycardias: insights from an atrial flutter ablation registry

Shunmuga Sundaram, Anees Thajudeen, SP Abhilash, VK Ajitkumar, JA Tharakan, Narayanan Namboodiri

Sree Chitra Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India

Background & Objectives: Long term results of radiofrequency (RF) catheter ablation for macro-reentrant atrial arrhythmia are affected by varying patient and substrate characteristics. We studied the electrophysiological characteristics of patients with macro-reentrant atrial tachyarrhythmia and determined the incidence and predictors of atrial fibrillation (AF) during follow up in these patients

Materials & Methods: All patients who underwent radiofrequency ablation for macro-reentrant atrial tachycardia between 2003 and 2011 were included. 47 patients satisfied the inclusion criteria. Mean age ofthe study population was 50.34 years. Mean follow up duration was 52.36 months. 49% had structural heart disease. 85% had typical isthmus dependent atrial flutter and 15% had atypical (isthmus non-dependent) flutter.

Results: Immediate procedural success could be achieved in 88.4% of patients. Event free survival (either atrial flutter or fibrillation) at the end of 124 months was 66%. 13.2% ofthe patients developed AF on follow up. Risk estimate analysis for the predictors of occurrence of AF showed risk ratio of14.8 (95% CI 1.4-154.9) for the presence of pacemaker, 10.33 (95% CI 1.6102.58) for previous history ofAF, Furthermore, PR interval duration was significantly higher in the patients who developed AF (174.3ms vs. 205.7ms; p value 0.017).

Conclusion: During long-term follow up of patients who had undergone RF ablation of macroreentrant tachyarrhythmias, AF develops more commonly in patients with underlying sick sinus syndrome, history ofAF or prolonged PR interval. All these markers may represent more advancedunderlying atrial conduction abnormalities.

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Long term outcome of atrial flutter ablation in surgically corrected ASD patients

Z. Muhammad, S. Kaur, A. Hussin, R. Rebo, A. Ahmad Said, S. Ahmad Saat, A. Zunida, R. Omar

Department of Cardiology, Institut Jantung Negara, Kuala Lumpur, Malaysia

Background: Up to 20% of atrial septal defect (ASD) patients who had surgical correction will develop atrial flutter (AFL) by the age of40. Patients tended to be very symptomatic and the AFLs were very difficult to control with medical therapy. We aim to characterize the long term outcome ofradiofrequency ablation (RFA) and incidence ofrecurrence in patients post ASD repair.

Method: Eleven consecutive patients undergoing RFA for AFL after surgical ASD repair were included. They were prospectively followed up. Clinical symptoms, 2D echocardiography, electrocardiograms, medications, and 24 hour holter were recorded every 6 months.

Results: There were 14 RFA procedures done. Time from surgical repair to RFA was 21+9 years. Mean age was47.2 + 14.4years, mean leftventricular ejection fractionwas 51.8+15.2 % andmean duration of follow-up was 6.1 +3.5 years. RFA was performed using a cool tip irrigated catheter with a 3D mapping system in 71.4% (10/14) and conventional RFA in 28.6% (4/14) procedures. 8 patients (63.6%) had Cavo-Tricuspid Isthmus (CTI)-dependent AFL circuits, including 4 patients with combination of either CTI and Upper Loop circuits (2) or CTI and Lower Loop circuits (2). 2 (18.2%) patients had Non CTI-dependent AFL, involving posterolateral and upper loop circuits. One patient had an unsuccessful FRA procedure. The immediate success rate was higher with the 3D mapping system, 100% (10/10) versus 50% (2/4) with the conventional RFA method. Mean procedural time was 161.4 + 82.7 minutes and mean fluoroscopy time was 28.0 + 27.2 minutes. At 6.1 years of follow up, 3 patients (18.2%) had recurrence of AFL, mean time to recurrence was 33.1 + 29.7 months. 2 were successfully ablated with repeat 3D mapping and one patient refused further invasive therapy. Total of 3 patients (18.2 %) developed atrial fibrillation. There was no incidence ofstroke or heart failure.

Conclusion: RFA of AFL in ASD patients following surgical repair is feasible, safe and has a high success rate using the 3D mapping system, with a low incidence ofrecurrence. Majority ofthe AFL utilized the CTI as part of the macro re-entry circuit with combination of either upper loop or posterolateral wall. RFA to critical area of these circuits, even by conventional method, tend to have high success and low recurrence rates.

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Pouch depth is the sole factor affecting the radiofrequency duration and energy for right atrial cavotricuspid isthmus catheter ablation

K. Kujra

Hyogo Prefectural Amagasaki Hospital, Japan Aim: The aim of this study was:

(i) to evaluate the precise anatomy ofthe sub-Eustachian pouch using intracardiac echocardiography

(ICE),

(ii) to explore whether the pouch depth influences the radiofrequency (RF) duration and energy of right atrial Cavotricuspid Isthmus (CVTI) ablation, and (iii) to define the cutoffvalue for a deep-pouch-specified ablation strategy.

Methods: Forty-seven atrial fibrillations (AF) patients were included. With intra-operative ICE, the isthmus length and pouch depth ofthe lateral aspect ofthe CVTI were evaluated. After a standard AF ablation procedure, a CTVI ablation was performed along the lateral isthmus. If bidirectional block couldnot be achieved despite linear lesions, the ablation catheter was deflected more than 90 degree to ablate deep inside the pouch (& knuckle-curve ablation).

Result: The isthmus length was 34.2&amp;amp;amp;plusmn;9.0mm and pouch depth 3.0&amp;amp;amp;plusmn;2.3mm. In all cases successful bidirectional block could be achieved. A multivariate analysis revealed the pouch depth was the sole factor influencing the RF duration (p=0.0035) and RF energy (p=0.0042). Using a receiver operating characteristic curve, the optimal cutoffvalue ofthe pouch depth for the &amp;amp;amp;rdquo;knuckle-curve ablation&amp;amp;amp;quot; was 3.7mm with an 83% sensitivity and 77% specificity.

Conclusion: The sub-Eustachian pouch depth was the sole important factor influencing the RF duration and energy in CVTI ablation. If the pouch is deeper than 3.7mm, a deep-pouch-specified ablation strategy would be needed.

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Getting RV lead at thinner part of interventricular septum tends to shorten paced QRS duration with less dyssynchrony

D. Volkov, D. Lopin, GIIGUS NAMNU

GI IGUS NAMNU, Ukraine

Background & Objectives: The preferable spot of RV pacing is still controversial. Our aim was to investigate a correlation between QRS duration, dyssynchrony indexes (DI) and position of pacing lead in the interventricular septum (IVS) in bradyarrhythmic RV pacing depending on relative IVS thickness (RTIVS).

Methods: 76 patients with bradyarrhythmias treated with DDD and VVI pacing were involved (age 72.6±5.5 yrs, males n=24). Location of RV lead in IVS was proved by EchoCG (RVOT - 28%, n=21, mid - 51%, n=39 and low - 21%, n=16). RTIVS in the lead spot was calculated by equation RSWT=h/H, where (h) septum thickness at the lead spot, (H) - average septum thickness, as H=S/L, where (S) - septum square, (L) - septum longest longitudinal dimension (picture).

■I RSWT = h/H A1 H=S/L

DI were assessed as deviation of time-to-peak systolic velocity (Ts-SD) and longitudinal and circumferential strain and strain rate (Long-S, Long-SR, Circ-S, Circ-SR).

Results: Average QRS duration was 155±17ms in RVOT, 143±15ms in mid-IVS and 152±18ms in low-IVS. In patients with lead implanted into the thinner part of IVS (RTIVS < 1.0, n=31) QRS was shorter than those with RTIVS > 1.05 (n=25) 142±15 ms vs. 153±17 ms, as well as myocardial performance by DI was better in comparison with the leads in the thicker part ofIVS.

Conclusion: Getting RV lead at thinner part of IVS tends to shorten paced QRS duration and lower levels ofDI. RVOT was mostly suboptimal pacing site because ofthicker IVS, longer paced QRS and impaired DI.

Is right ventricular outflow tract (RVOT) septal pacing better than right ventricular apical (RVA) septal pacing with regard to long term left ventricular function and mechanical synchrony?

Gaurav Ganeshwala, K.U.Natarajan, Navin Mathew, Rajiv C.

Department oof cardiology, Amrita Institute oof Medical Sciences, Kochi, India

Background & Objective: RV apex (RVA) has been the preferred site for pacemaker lead placement since the advent of transvenous pacing. However, RVA pacing results in electrico-mechanical dyssynchrony and worsening of LV function. It is hypothesized that RV outflow tract (RVOT) septal pacing is a safer alternative due to more physiological activation of myocardium. We tried to study the long term effects of RVOT septal versus RVA pacing on cardiac synchrony and overall LV function.

Methods: 48 patients (RVA =27 and RVOT= 21) who were on permanent cardiac pacing (DDD or VVI) for more than 1 year were enrolled. All these patients had structurally normal heart and normal LV systolic function at the time of pacemaker implantation. Baseline echocardiography parameters before pacemaker implantation were obtained from the old medical records. All these patients underwent detailed echocardiography assessment including 2D, M-mode, doppler studies and dyssynchrony analysis (including pulse tissue doppler, tissue velocity imaging and speckle tracking strain imaging).

Results: The average duration of pacing was 6.33±3.2 yrs in RVA group and 3.95±2.43 yrs in RVOT group. The RVA group had wider QRS duration compared to RVOT group (152.96 ms v/ s 142.38 ms). Pulse tissue doppler, tissue velocity imaging and speckle tracking systolic radial strain analysis revealed better Intra-ventricular LV synchrony in the RVOT group compared to RVA group (p<0.05). The most consistent pattern of LV dyssynchrony was seen between septum and lateral walls. The higher ventricular dyssynchrony noted in the RVA group was related to the higher cumulative % of pacing and not to the longer duration of pacing. There was a trend of better inter-ventricular synchrony in the RVOT group (p=0.07). The LA dimension and MR were significantly higher in RVA group compared to RVOT group (p<0.04). However, there was no significant difference in LV dimensions, LVEF and cardiac index.

Conclusion: RVOT septal pacing was associated with better echocardiographic indices of inter and intra-ventricular mechanical synchrony compared to the RV apical pacing group. Hence, if permanent pacing is indicated, RVOT septum may be the preferred site over RVA pacing in maintaining better cardiac synchrony, till better options are available.

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Paced QRS duration as a predictor for clinical heart-failure events during right ventricular apical pacing in patients with idiopathic complete atrioventricular block

Shaojie Chen1, Yuehui Yin1, Xianbin Lan \ Zengzhang Liu 1 Zhiyu Ling 1 Li Su 1 Marcio Galindo Kiuchi2, Xiaoli Lill3, Bin Zhong4, Mitchell W Krucoffs'6

Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

Hospital Centrocardio, Rua Domingues de Sa, n° 410-Icarai, Niteroi, Rio de Janeiro, 24220090, Brazil

Department of Cardiology, Chongqing Zhongshan Hospital, Chongqing, China Department of Cardiology, The Fifth People's Hospital of Chongqing, Chongqing, China Duke University Medical Center, 508 Fulton Street, Durham, North Carolina, 27705, USA Duke Clinical Research Institute, 27705, USA

Background: Long-term right ventricular apical pacing (RVAP) is associated with impaired cardiac function.

Objective: This study aims to investigate the predictability of paced QRS duration (pQRSd) in heart-failure events among patients with RVAP.

Methods: 194 patients with complete atrioventricular block receiving pacemaker treatment were enrolled and stratified to group 1: pQRSd < 160ms, n=53; group 2: 160<pQRSd < 190ms, n=97; and group3: pQRSd>190ms, n=44. Study outcomes were heart-failure events, changes in pQRSd and changes of left ventricular ejection fraction (LVEF).

Results: During the 3-year follow-up, the incidence of heart-failure events were 9.4%, 27.8% and 56.8% in group 1, 2, 3 respectively (P < 0.001). Among the patients without heart-failure events, the pQRSd at 3 years remained longer than that at baseline (162.1±22.6 versus 160.9±22.1ms, P < 0.05). While among patients who experienced heart-failure events, the prolonged pQRSd at 3 years seem more pronounced as compared with baseline (184.1±21.1 versus 179.8±21ms, P < 0.001). Linear regression demonstrated that decrease of LVEF was positively correlated with pQRSd over time (RR: 0.423; P < 0.05). Receiver operation curve showed that the cut-offvalue of pQRSdwas 165ms with a sensitivity of0.789.

Conclusion: A prolonged pQRSd has a detrimental effect on long-term cardiac function during RVAP in patients with complete atrioventricular block. pQRSd could be a useful predictor to identify patients who are at risk for heart-failure events during RVAP.

Acute haemodynamic and hormonal effects of right ventricular apical pacing compared to right ventricular outflow tract pacing in non-bradycardic patients with normal ventricular function

P.A. Gould, K. Ng, Y. Chacko, S. Doneva, D. Korczyk, G. Dimeski

Princess Alexandra Hospital, University of Queensland Brisbane, Australia

Background & Objectives: Research suggests right ventricular apical pacing (RVA) maybe deleterious to ventricular function and accordingly alternative sites have been suggested such as the right ventricular outflow tract (RVOT). In this study we sought to compare the acute haemodynamic and hormonal response of RVA with RVOT pacing in patients with normal ventricular function.

Methods: In 21 patients undergoing an electrophysiological study, baseline hemodynamics and Brain Natriuretic Peptide (BNP) were measured from the femoral vein, artery and coronary sinus. A trans-cardiac BNP gradient was also calculated. Patients were then randomly assigned to RVA or RVOT pacing 10 beats/min above baseline for 10 minutes and after a 15 minute wash-out period crossed over to the alternate site with the same protocol and the measurements repeated on each occasion.

Results: Patients were aged 48 +/-19 years with a female predominance (71%) and mean LVEF of 61+/-5%. There was a significant increase in pulmonary capillary wedge pressure (PCWP) from baseline with both sites of pacing (p < 0.001 in both) and an increase in systolic blood pressure with RVA pacing only (RVA p=0.001, RVOT p=0.06). Arterial BNP rose from baseline significantly with both sites of pacing (RVA p<0.001, RVOT p=0.005) but with no difference between sites. No other haemodynamic or hormonal differences were observed between the two sites.

Conclusion: This study demonstrates a similar acute hemodynamic and hormonal profile for RVOT versus RVA pacing, both with significant increases in PCWP and arterial BNP. This may have clinical implications in chronic right ventricular pacing.

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Left atrial responses to acute right ventricular apical pacing in patients with sick sinus syndrome

Kyoung-Im Cho, Tae-Joon Cha, IK Shim, Jung-Ho Heo, Hyun-Su Kim, Jae-Woo Lee

Division of Cardiology, Department of Internal Medicine, Kosin University School of Medicine, Busan, South Korea

Background: Chronic right ventricular apical (RVA) pacing can lead to an increased risk of heart failure and atrial fibrillation, but the acute effects of RVA pacing on left atrial (LA) function are notwell known.

Methods: Twenty-four patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were included. All patients received dual-chamber pacemaker implants with the atrial lead in the right atrial appendage and the ventricular lead in the right ventricular (RV) apex. Transthoracic standard and strain echocardiography (measured by TDI: tissue Doppler image, and STI: speckle-tracking image) were performed to identify functional changes in the LV and LA before and after one hour ofRVA pacing.

Results: The LA volume index did not change after pacing; however, the ratio of peak early diastolic mitral flow velocity (E) to peak early diastolic mitral annular velocity (Ea) was significantly increased and peak systolic LA strain (Sm), mean peak systolic LA strain rate (SmSR), peak early diastolic LA strain rate (EmSR), and peak late diastolic LA strain rate (AmSR) were significantly reduced after RV pacing. LV dyssynchrony, induced by RV pacing, had a significant correlation with E/Ea, Sm, and SmSR after pacing. E/Ea also had a negative correlation with Sm and SmSR after pacing. Multivariate regression analysis identified LV dyssynchrony and E/Ea as important factors that affect Sm, SmSR, EmSR, andAmSR after acute RVA pacing.

Conclusions: Acute RVA pacing results in LA functional change and LV dyssynchrony and higher LV filling pressures reflected by E/Ea are important causes of LA dysfunction after acute RVA pacing.

Keywords: echocardiography; left ventricular function; left atrial function; cardiac pacing, artificial

OP 22-6

Long-term effect of right ventricular outflow tract versus apical pacing on cardiac function and synchrony

Jun Yu, Keping Chen, Ruohan Chen, Shu Zhang

Cardiovascular Institute and FuWai Hospital, Chinese Academy oof Medical Sciences, Peking Union Medical College, Beijing 100037, China

Background: Right ventricular outflow tract (RVOT) has been encouraged as an alternative pacing site to avoid long-time detrimental effect induced by right ventricular apical (RVA) pacing, but there hasn't been definitely evidence on the benefit of RVOT pacing. This study aimed to evaluate the long-term impact ofRVOT versus RVA pacing on cardiac function and synchrony.

Methods: 42 patients with inclusion criterion were randomly assigned to receive a screw-in lead either in RVA (n=14) or in RVOT (n=28). 3D-Echocardiography, electrocardiogram, and X-ray were used to determine the pacing sites. Cardiac function, inter-and intra-ventricular dyssynchrony were evaluated. Patients with VP%>10% were enrolled into the final analysis.

Results: After mean follow-up of 7.1±0.4 years, paced QRS interval for RVA pacing was longer than RVOT pacing (155.8±7.1ms vs 143.8±14.4ms, p<0.05). LV end-diastolic diameter (44.5±5.5mm vs 47.6±1.8mm, p>0.05), LV ejection fraction (66.1±5.0% vs 67.0±4.1%, p>0.05), and intravenricular dyssynchrony (29.9±15.6ms vs 27.3±14.1ms, p>0.05) showed no significant difference between the two groups. Tei index and interventricular dyssynchrony were worse in RVAP than in RVOT (0.7±0.2 vs 0.5±0.2; -15.9±20.5ms vs -9.1±19.0ms, respectively). Compared with baseline, Tei index in RVA pacing was impaired significantly (0.7±0.2 vs 0.5±0.08, p<0.01) but not RVOT pacing (0.5±0.2 vs 0.4±0.03, p>0.05); both RVA and RVOT pacing were associated with impaired interventricular (-15.9±20.5ms vs 11.3±4.9ms, -9.1±19.0ms vs 9.3±6.3ms, respectively, p<0.05)and intraventricualr synchrony (29.9±15.6ms vs 9.7±1.1ms, 27.3±14.1ms vs 8.5±2.5ms, respectively, p<0.05).

Conclusions: RVOT pacing didn't show much superiority over RVA pacing in cardiac function and synchrony. Bothpacing groups showedworse dyssynchronythan baseline.

Keywords: Right ventricular apical pacing, right ventricular outflow tract, cardiac function, synchrony

OP 10-1

OP 10-2

Does the peri-procedural anticoagulation management for AF affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging (DMRI) in patients undergoing atrial fibrillation ablation with open irrigated radiofrequency energy?

Luigi Di Biase, Fiorenzo Gaita, Elisabetta Toso, Pasquale Santangeli, Prasant Mohanty, Neal Rutledge, Xue Yang, Sanghamitra Mohanty, Chintan Trivedi, Rong Bai, Justin Price, Rodney Horton, Joseph Gallinghouse, Salwa Beheiry, Jason Zagrodzky, Robert Canby, Jean François Leclercq, Franck Halimi, Marco Scaglione, Federico Cesarani, Riccardo Faletti, Javier Sanchez, J. David Burkhardt, Andrea Natale

Introduction: Silent thromboembolic lesion (STL) has been reported in 14% ofthe cases following catheter ablation of atrial fibrillation with radiofrequency energy (RF) and with waarfarin discontinuation before AF ablation procedures. We sought to determine if the periprocedural anticoagulation management could affect the prevalence of STL following RF ablation with open irrigated catheter.

Methods: Consecutive patients undergoing RF ablation for AF with &ldquo;therapeutic&rdquo; warfarin and receiving heparin bolus before transseptal (group 1, n=146) were compared with a group ofpts that had protocol deviation in terms ofmaintaining the therapeutic pre-procedure INR ( patients with subtherapeutic INR) and/or failure to receive pre-transseptal heparin bolus infusion (non-compliant population, group 2, n=134) and with a group of patients undergoing RF ablation with warfarin discontinuation bridged with low weight molecular heparin (group 3, n=148). All patients underwent preablation and postablation (within 24 hours) dMRI. All patients had to maintain ACT above 300 secs during the entire procedure.

Results: STL was detectedin2%(3/146) in group 1, 7% (10/134) in group2andin 14% (21/148) in group 3 respectively (p &lt;.001). &ldquo;Therapeutic INR&rdquo; was strongly associated with a lower post-procedure embolic lesion. Multivariable analysis demonstrated non-paroxysmal AF (odds ratio 3.8 (1.5 to 9.7), p=0.005) and compliance to protocol (odds ratio 2.8 (1.5 to 5.1), p&lt;.001) as the only significant predictors ofischemic events.

Conclusion: This study shows that strict anticoagulation protocol adherence, significantly reduces the prevalence of STL following catheter ablation of atrial fibrillation with RF energy.

Safety of right-sided atrial flutter ablation performed under novel oral anticoagulants

Jean-Francois Sarrazin, Francois Philippon, Jean Champagne, Franck Molin, Isabelle Nault, Louis Blier, Gilles O'Hara

Quebec Heart and Lung Institute, Quebec, Canada

Background/Objectives: Adequate anticoagulation is required for cardioversion of atrial flutter (AFL). Limited literature is available on the safety of right-sided AFL ablation performed under novel oral anticoagulants (NOAC).

Methods: Over 2 years, 145 consecutive anticoagulated patients (age 65±12 years, CHADS2 score 1.4±1.1, left atrial volume 37±12ml/m2) underwent 150 AFL ablations for suspected right-sided AFL at a single tertiary care center. One hundred and two procedures were performed on warfarin and 48 procedures on NOAC (dabigatran n=40 or rivaroxaban n=8).

Results: Baseline characteristics were similar. The INR was 2.3±0.4 in the warfarin group. Dabigatran (132±20mg BID) was stopped for 2.1±0.9 doses before the procedure (TCA 34±6 sec), and rivaroxaban (19±2mg daily) for 1.4±0.8 doses. NOAC were resumed on the same day ofthe procedure. The number of patients requiring TEE or bridging was similar in both groups. Fewer sheaths were used in NOAC patients (2.6±0.5 vs. 3.4±0.7; p<0.001). Patients on warfarin were less likely to receive IV heparin (p<0.001). Cardioversion was performed in 55% (83/150) of procedures (36 procedures by electrical/chemical cardioversion and 47 by conversion to sinus rhythm during ablation). Bidirectional block was obtained in 92% with a conduction time of 159±32 msec. No bleeding or thromboembolic complication occurred in patients on NOAC, while one major and 6 minor bleeding complications occurred in patients on warfarin. The total complication rate tended to be lower in patients on NOAC (0% vs. 7.8%; p=0.055) with a follow-up of6.2±6.8 months.

Conclusion: Right AFL ablation can be performed safely under novel oral anticoagulants.

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OP 10-5

Pulmunary vein isolation in patients with atrial fibrillation with peri-procedural dabigatran

Amitabh Yaduvanshi, Sanjib Patra, Vikas Kataria, Mohan Nair

Department of Cardiology, Saket City Hospital, New Delhi, India

Background: Pulmunary Vein isolation (PVI) in AF ablation is associated with high incidence of transient ischemic events (TIA) and bleeding complications. Until recently, oral anticoagulation has been stopped with cross over to low molecular weight heparin prior to ablation. We evaluated the safety ofPVI using uninterrupted oral anticoagulation in the periprocedure period.

Methods and Results: Forty five patients (33 M, 12 F) underwent PVI isolation for AF from April 2011 to March 2013. Of these 29 were on warfarin and 16 were on dabigatran 110mg twice a day prior to the procedure. In the warfarin group the drug was continued uninterrupted and in the dabigatran group the morning dose of the drug was skipped prior to the procedure, with the drug being restarted in the evening. The dose of heparin used during the procedure was similar in both groups, targeting an intraprocedure ACT of 300 secs. Total thrombotic and bleeding complications were similar in both groups with 4 minor bleeding complications in warfarin group and one TIA and one hematoma in the dabigatran group (p =0.45).

Conclusion: Dabigatran in dose of 110mg twice a day can be used safely in Indian patients undergoing PVI without interrupting or switching over to another anticoagulant. There was a trend towards lesser bleeding complications with dabigatran as compared to un-interrupted warfarin (p=0.36) but this was offset by one TIA in the dabigatran group.

Cost-effectiveness analysis of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation: a population-based study in ttaiwan

Chieh-Yu Liu, Tze-Fan Chao2, Shih-Ann Chen2, Hui-Chun Chen

School of Nursing, National Taipei University of Nursing and Health Sciences, Taiwan 2Cardiology Division, Medicine Department, Taipei Veterans General Hospital, Taiwan

Background & Objectives: This study was aimed to investigate the cost-effectiveness of stroke prevention in patients with nonvalvular atrial fibrillation between novel oral anticoagulants apixaban 5 mg, dabigatran 110 mg, and rivaroxaban 20 mg compared with warfarin.

Methods: The Markov decision-analysis and Monte Carlo probabilistic sensitivity analysis were used and the data were from the National Health Insurance (NHI) claims database in Taiwan from 2008-2010 and published results to evaluate lifetime costs, life years (LY) and quality-adjusted life-years (QALY). Study population's demographic parameters were calculated from the NHI claims database.

Results: This study recruited 151,672 prevalence-based cases and 91,258 incidence-based cases during 2008-10. The cost-effectiveness acceptability curves (CEAC) analysis showed that apixaban had more incremental cost -per QALY and -per LY gained than warfarin, dabigatran(110mg) and rivaroxaban, however, apixaban can provide more incremental QALY (+0.19, +0.105, +0.048) and longer incremental LY (+0.18, +0.12, +0.06). Apixaban had slightly more number needed to treat (NNT) for stroke, however, apixaban showed dominant results (better or more) for number needed to harm (NNH) for hemorrhagic events than warfarin and rivaroxaban.

Conclusion: The results of this population-based simulation study showed that apixaban can provide better QALY and longer life years than warfarin, dabigatran 110mg and rivaroxaban, although along with slightly higher life time costs (+USDS228-459 than dabigatran 110mg and rivaroxaban, +USD$2,153 for warfarin). Apixaban was still considered cost-effective alternatives to warfarin, dabigatran (110mg) and rivaroxaban for the prevention of stroke prophylaxis in patients with nonvalvular atrial fibrillation.

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OP 10-6

Dabigatran use in atrial fibrillation patients at high risk of stroke: a single centre experience

L B Yap, BIRusani, D Umadevan, Z Muhammad, A Hussin, S Kaur, R Omar

National Heart Centre, Malaysia

Background: In 2009, our centre began to use the novel anticoagulant, Dabigatran, for stroke prevention in patients with atrial fibrillation (AF).

Objective: We aimed to retrospectively study the efficacy, adverse effects and discontinuation rate in our 'real world' patients on dabigatran.

Method: Medical records of a total of 518 patients who were prescribed Dabigatran were reviewed. Patient characteristics and clinical data were collected.

Results: The mean age was 68 (range 20-91) years. There were 74% of patients with Paroxysmal AF,11% with persistent and 14% with permanent AF. Dabigatran of 110 mg strength were prescribed for 210 (40.5%) patients and 308 (59.5%) patients were prescribed the 150 mg dose. The average follow-up duration was 315 (range: 1 - 2526) days. There were 17 (3.3%) patients with minor bleeding and had 2 (0.4%) had major bleeding episodes. 20 patients (3.9%) developed dyspepsia, the commonest side effect. The adverse effect rates were lower than those seen in the RE-LY trial. None of the patients had an ischaemic stroke. 1 (0.19%) patient had a haemorrhagic stroke. Out of 518 patients, 150 patients (29%) were switched to dabigatran from warfarin due to patient preference. The overall discontinuation rate was 16% after a median 262 days of treatment with dabigatran.

Conclusion: Patients on dabigatran had low rates of adverse effects of dyspepsia and bleeding. Patient preference for a convenient alternative to warfarin has contributed significantly to dabigatran's use. Dabigatran is a safe and effective drug to prevent stroke in among AFpatients.

OP 04-1

OP 04-2

Ganglionated plexi ablation directed by high-frequency stimulation and complex fractionated atrial electrograms for paroxysmal atrial fibrillation

Artem Strelnikov, Denis Losik, Sevda Bajramova, Vgeny Pokushalo

Novosibirsk State Research Institute of Circulation Pathology, Russia

Introduction: The effectiveness of ganglionated plexi (GP) ablation in patients with AF is ambiguous. Some researchers had already suggested that additional identification of complex fractionated atrial electrograms (CFAE) around the areas with a positive reaction to high-frequency stimulation (HFS) might improve the accuracy of GPs boundaries location, then enhancing the success rate of ablation. The purpose of this study was to assess the safety and efficacy ofGP ablation directed by HFS and CFAE in patients with paroxysmal AF (PAF).

Methods & Results: Sixty-two patients with paroxysmal AF (age 57 & 8 years) underwent ganglionated plexi (GP) ablation. Ablation targets were the sites where vagal reflexes were evoked by HFS and additional extended ablation CFAE area around the areas where vagal reflexes were evoked. At 12 months, 71% of patients were free of symptomatic AF. At 3 months after ablation the rMSSD and HF were significantly lower in patients without AF recurrence (p=0.0001 and p=0.004). The LF/HF ratio was significantly higher in patients without AF recurrence (p=0.02).

Conclusions: Enhanced GP ablation directed by high-frequency stimulation and complex fractionated atrial electrograms can be safely performed and enables maintenance of sinus rhythm in majority of patients with PAF for a 12-month period. Denervation of the intrinsic cardiac autonomic nervous system may be the preferable target ofcatheter ablation ofatrial fibrillation.

Ganglionated plexi ablation combined with pulmonary vein isolation improves outcome of catheter ablation in patients with longstanding persistent atrial fibrillation: a prospective randomized comparison

Sevda Bayramova, Artem Strelnikov, Denis Losik, Evgeny Pokushalov, Alexander Romanov, Sergey Artyomenko, Alexey Turov, Natalia Shirokova, Alexander Karaskov

Arrhythmia Department and EP Laboratory, Novosibirsk State Research Institute of Circulation Pathology, Russia

Introduction: Pulmonary vein isolation (PVI) is an established strategy for paroxysmal atrial fibrillation (AF) but seemed to be less effective in patients with persistent AF. Some researchers had already suggested that additional ganglionated plexi (GP) ablation might improve the success rate. The aim of our study was to assess the maintenance of sinus rhythm (SR) in patients with longstanding persistent AF at least 3 years using 2 different ablation strategies, PVI plus linear lesions (LL) versus PVI plus GP ablation.

Methods: Two hundred sixty four consecutive patients with longstanding persistent AF were randomly assigned to 2 different ablation schemes: PVI plus LL (n=132) and PVI plus GP ablation (n=132). Primary end point was to assess the maintenance of SR after procedures in a long-term follow-up ofat least 3 years.

Results: All cases underwent the procedure successfully. PVI was achieved in all cases. With a single procedure at the 12-month follow-up, 47% of patients treated with PVI plus LL were in SR, whereas at the 3-year follow-up, 34% maintained SR; using the PVI plus GP with a single procedure at the 12-month follow-up 54% of patients were in SR (p=0.068), whereas at the 3-year follow-up, 49% remained in SR (p=0.021).

Atrial flutter was more frequent in the group of PVI plus LL than in PVI plus GP ablation group (11% versus 4%, P=0.036). After a second procedure, the long-term overall success rate was 52% with PVI plus LL and 68% with PVI plus GP ablation (p=0.018).

Conclusions: The difference between PVI plus LL and PVI plus GP ablation strategy is not statistically significant at 12 months in patients with longstanding persistent AF, whereas the difference becomes statistically significant in the longterm follow-up because ofthe higher number ofrecurrences in the PVI plus LL group.

OP 04-3

OP 04-4

Fractionated atrial potential at anatomical ganglionated plexi sites in atrial fibrillation - investigation by electrical anatomical mapping system

D. Ishigaki, T. Arimoto, T. Iwayama, D. Kutsuzawa, N. Hash

Yamagata University School of Medicine, Japan

Background: The association between fractionated atrial potential (FAP) and ganglionated plexi (GP) has been reported previously. We investigated whether FAP existed in the vicinity of anatomical GP sites in patients with atrial fibrillation (AF), using three dimensional electroanatomical mapping system.

Methods & Results: Consective 20 patients (17 men, 3 women, mean age 57.2±8.5 years) with drug resistant AF underwent pulmonary vein isolation and GP ablation were enrolled. Mapping of FAP during AF was performed at least 100 points in the whole left atrium, particularly at the locations where GP are commonly located. High frequency stimulation was also performed to confirm vagal response (VR) at the sites of Marshall tract, superior left, anterior right, inferior left and inferior right GP. FAP area was confirmed 21.7±12.9% of whole left atrium. At the site of the Marshall tract GP, FAP were recorded in 9 of20 patients (45%), and in 10 (50%), 11 (55%), 8 (40%), and 8 (40%) patients at the sites of superior left, anterior right, inferior left and inferior right GP, respectively. Among total 100 GP sites, positive VR was observed at 63 sites and negative VR was 37 sites. FAP was recorded in 36 of 63 (57%) positive VR sites and in 10 of 37 (27%) negative VR sites (p < 0.001).

Conclusion: FAP at anatomical site of GP, which confirmed by positive VR, were identified in 57% patients with AF. This finding indicated that the significant relationship between FAP and anatomical GP sites.

Surgical ablation by unilateral approach (left chest) for lone atrial fibrillation: a single center experience in 100 consecutive patients

Ju Mei

Shanghai Jiaotong University, China

Objective: We presented the technique of our minimally invasive surgical ablation by unilateral approach (left chest) and the follow up results of 100 patients with lone atrial fibrillation

Methods: 100 patients with lone atrial fibrillation underwent this therapy between October 2010 and September 2012. These patients were aged between 30 and 81 including 58 males and 42 females. Among them, 58 were with paroxysmal, 32 were with persistent, and 10 were with longstanding atrial fibrillation. The procedure was performed on the beating heart, through three ports on left chest wall. Pulmonary vein isolation and ablation ofthe left atrium was achieved by bipolar radiofrequency ablation. Ganglionic plexus ablation was made by the ablation pen. Left atrial appendage was excluded.

Results: Durations of their procedures were 118.3A±37.3 mins. No conversion to sternotomy or pacemaker implantation occurred and none ofthe patients died. Their hospital stay were 7.5 A±3.2 days. The mean follow-up duration were 8.9A±4.7months. 92(92%) of all patients were in sinus rhythm. 8 patients could not maintain sinus rhythm. Thrombus in the left atrium and stenosis ofpulmonary vein were not found after their procedures.

Conclusions: This new technique was safe and effective, so it deserves to be promoted for the treatment of lone atrial fibrillation.

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OP 04-5

Efficacy of catheter ablation of atrial fibrillation using robotic navigation

Fahd K. Chahadi1, Cameron B. Singleton, John Bowyer1, Andrew D. McGavigan1'2

Department of Cardiovascular Medicine, Flinders Medical Centre & Faculty of Medicine, Flinders University, Australia

Introduction: Remote navigation for catheter ablation of atrial fibrillation has several potential benefits, but efficacy data are limited.

Methods: We present data on 79 consecutive patients undergoing de novo catheter ablation for drug resistant atrial fibrillation using the Hansen Sensei Robotic System and report primary endpoint of drug free, single procedure success at 12 months. Secondary endpoints of arrhythmia free success at 12 months with more than one procedure with and without drugs are also reported.

Results: 90 procedures performed in 79 patients 46 paroxysmal (P), 33 non-paroxysmal (N-P). 12 month, single procedure drug-free success of 80.4% (P) and 57.6% (N-P). Following index procedure, 4/46 and 6/33 were well controlled on previously ineffective anti-arrhythmic drug (AAD) and declined a second procedure. 11 patients underwent a second procedure, increasing success rates to 84.8% (P) and 69.7% (N-P) with a mean of 1.09 and 1.18 procedures per patient respectively (93.5% and 87.9% including AADs).

Conclusions: Ablation of atrial fibrillation using the Hansen Sensei Robotic System is associated with high rates ofsuccess at 12 months.

OP 04-6

Surrogates markers have limited ability for predicting pre-ablation contact force and lesion efficacy during catheter ablation of atrial arrhythmias in humans

Saurabh Kumar,1 Joseph B. Morton/'2Martin Chan, Justin M.S. Lee,Matias Yudi,1 Michael C.G. Wong,1 Karen Halloran, Steven J. Spence, Haris M. Haqqani J Peter M. Kistlerf12'4 Jonathan M. Kalmtan12

Department of Cardiology & Department of Medicine, The Royal Melbourne Hospital & University of Melbourne, Victoria; Department of Cardiology, The Prince Charles Hospital & School of Medicine, The University of Queensland, Queensland; Department of Cardiology, Alfred Hospital & Baker IDI, Melbourne, Australia

Background & Objectives: Catheter-tissue contact force (CF) is inferred using surrogate markers. We evaluated (i) correlation of these markers with real-time CF & (ii) their ability to predict effective lesion formation.

Methods: 34 patients underwent RF ablation for AF/AFL using a novel CF-sensing catheter (operators blinded to CF). Average CF/force-time integral (FTI) were logged. Surrogate markers such as catheter movement, EGM amplitude/width & abatement with RF, baseline impedance/ fall with RF, max. power, tip temperature & total energy delivered were used to infer contact. An effective lesion was identified using previously validated EGM criteria for lesion transmurality. 2265 lesions were evaluated.

Results: (i) Using surrogate markers up to 30% of lesions had low CF (<10g) with marked CF variability within & between different PV regions & the CTI (P<.05) esp. in critical areas such as the carina/left ant PVs which had the lowest CF; (ii) baseline impedance & fall poorly correlated with CF (R=0.07/R=0.32) & couldonly identifylow CF 15s afterRFonset (iii)pre-ablationEGM amplitude/width poorly correlated with CF (both R=0.2); (iv) of all parameters, only FTI & total energy delivered independently predicted effective lesion formation (P<.001); (v) av. CF >16g or FTI >404 g*s was required to create an effective lesion (sensitivity/specificity >88%); (vi) low CF/FTI strongly correlated with RF time for PVI/CTI block (R=0.8) and incidence of acute reconnection (P<.001).

Conclusions: Surrogate markers are poor predictors ofreal-time CF and lesion efficacy during RF ablation in humans. CF has a critical influence on acute procedural outcomes.

OP 06-1

OP 06-2

Directed ablation of regions of high shannon entropy as potential marker of AF rotors: initial clinical experience

AN Ganesan, P Kuklik, A Brooks, Lauren Wilson, Sachin Nayyar, Rajiv Mahajan, Rajeev Pathak, DTwomey, P Sanders

Centre for Heart Rhythm Disorders, University oofAdelaide, Australia

Background & Objectives: Targeted rotor ablation has been postulated as a mapping strategy in AF. We have shown that high bipolar electrogram Shannon entropy (ShEn) distinguishes the pivot from periphery of rotors. We hypothesized that ablation directed at regions of high ShEn could slow or terminate AF.

Methods: We prospectively targeted ablation of regions of high ShEn in 9 peristent AF patients. (LA45±6mm, LVEF 52±5%). Patients in spontaneous or induced AF were mappedwith a 20-pole PentaRay catheter and NavX system (621±26 points/pt). Map points were exported to a PC where ShEn map was constructed. The top 10% of ShEn points were annotated on the NavX map to guide ablation. Ablation of pre-identified ShEn regions was performed after pulmonary vein antral isolation without CFAE or linear ablation. Endpoints were: (i) AF cycle length change; and (ii) AF termination.

Results: AF termination occurred in 6/9 cases, with 3/9 cases requiring cardioversion. 3/9 cases terminated during PVAI, with 2/3 of these cases coinciding with pre-specified high ShEn. 3/9 cases terminated during ablation in pre-specified high ShEn regions. Mean AFCL change post PV isolation was 11.8±13ms (p=0.07), and AFCL change post-ShEn ablation was 29.1±26ms (p=0.02). 6/9 cases remained in sinus rhythm at median follow-up 274±148 days .

Conclusion: Directed ablation of high ShEn regions, as a marker ofthe pivot zone ofAF rotors, may be associated with termination ofAF and/or AF cycle length slowing in selected AF patients, and requires further investigation in AF ablation.

Cryoablation of pulmonary veins for paroxysmal atrial fibrillation: comparison of acute and mid-term outcome between first and second generation balloon

Massimo Moltrasio, Osama Al-Nono, Gaetano Fassini, Antonio Dello

Centro Cardiologico Monzino, Italy

Background & Objectives: Cryoballon ablation (CA) for atrial fibrillation (AF) has been established as a promising approach for treatment of patients (PTS) with paroxysmal AF. Objective ofthe study is to compare acute and mid-term outcome between the first generation cryoballoon (1G-CB) and second generation cryoballoon (2G-CB)

Methods: We compared 66 consecutive pts with paroxysmal AF who underwent CA (34 pts with 1G-CB; 32 pts with 2G-CB). All pts underwent follow up with 7-day Holter and clinic evaluation every 2 months for the first 8 months after CA.

Results: There were no significant differences between 1G-CB and 2G-CB regarding age (62.8 ± 9.5 years vs 57.1 ± 12.1 years; p=0.06), left atrial areas (23.2 ± 4.8 cm2 vs 22.4 ± 5.2 cm2; p=0.57), left ventricular ejection fraction (62.8 ± 5.1% vs 62.3 ± 6.6 %; p=0.71) and presence of coronary artery disease (11% vs 12% of pts). Procedures performed with 1G-CB showed longer fluoroscopy times (56.3 ± 26.8 min vs 32.2 ± 13.5 min; p=0.00016) and longer procedure times (193.1 ± 52 min vs 162 ± 44.8 min; p=0.019). After 8 months of follow-up, freedom ofAF recurrences was seen in 82.6 % of 1G-CB pts and 92% of 2G-CB pts (p=0.30). There was one cerebral embolization among 1G-CB pts and one case of reversible phrenic nerve palsy for each group.

Conclusions: The 2G-CB reduced procedure and fluoroscopy times and effectiveness rate was greater than that seen with 1G-CB over 8 months of follow-up but with no statistically significant difference.

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OP 06-4

Contact force values during ablation for pulmonary vein isolation: analysis according to anatomy and operators

Roberto De Ponti, Raffaella Marazzi, Lorenzo A. Doni Jacopo Marazzato, Jorge A. Selerno-Uriarte

Department of Heart & Vessels, Ospedale di Circolo University of Insubria, Varese, Italy

Background & Objectives: The contact force (CF) now routinely measured during electrophysiology procedure. This study evaluates the variations in CF during ablation for pulmonary vein (PV) isolation (I) according to the site, operator and patient.

Methods: Twenty consecutive patients with atrial fibrillation undergoing the first PV-I were considered. PV-I was performed using CARTO 3 (Biosense Webster, USA) with imaging integration and an irrigated-tip catheter with mechanical contact force sensor (Thermocool, Smart-Touch, Biosense Webster, USA). The mean CF was evaluated for each 1-min, 30W application. The pulmonary vein antra were subdivided in 15 quadrants. Only two experienced operator aware ofthe CF were involved in this study.

Results: An overall number of 1,576 applications were delivered for PV-I with a mean CF value of 12.6±8.7 g. The CF values varied significantly in the different quadrants, with the posterior quadrant ofthe left superior PV being the one with the highest values (18.8±10.3 g) and the anterior quadrant ofthe right inferior PV being the one with the lowest (8.6±4.4 g). Between the two operators, the average of the overall values of CF were comparable, but the CF varied significantly for the two operators in 5 quadrants. The median value of CF per patient fluctuated from 7 to 13 g. Non complication was observed.

Conclusions: There is a wide variation ofthe CF values, even if the operator is aware of this parameter during the procedure. These variations depend on morphological (site and/or patient-specific) reasons and operators' attitude.

Clinical impact of anatomical variation of vein of marshall (V OM) on creating bi-directional conduction block at mitral isthmus after ethanol infusion into VOM

Naohiko KAWAGUCHI

Yokohama City Bay Red Cross Hospital, Japan

Backgrounds: Ethanol infusion (EI) into VOM is one of the new promising methods in atrial fibrillation (AF) ablation. Although the previous studies have reported the feasibility of ethanol infusion into VOM to create the bi-directional conduction block at mitral isthmus (MI), relationship ofthe effect ofEI into VOM with its anatomical variation remains still unknown.

Methods: Forty five consecutive patients who underwent AF ablation including EI into VOM from September 2012 to April 2013 were included. Coronary sinus (CS) venography was performed before EI in VOM. All patients were divided into two groups according to the position of VOM bifurcation from main CS; 32 patients with VOM arising from proximal part ofCS (group 1) and 13 patients from distal part ofCS (group 2). We subsequently performed radiofrequency catheter ablation (RFCA) at MI in case of incomplete conduction block across MI after EI into VOM. We evaluated the success rate of creating conduction block at MI by EI into VOM between two groups.

Results: The patients with bidirectional conduction block at MI achieved solely by EI into VOM were more frequently observed in group 2 than in group 1 (4 (31%) vs. 1 (3%), p=0.007). There was no significant difference between two groups of success rate of creating conduction block at MI requiring subsequent additional RFCA (11 (85%) vs. 27 (84%), p=0.98).

Conclusions: EI into VOM may be more effective in patients with VOM arising from distal part ofCS.

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OP 06-5

Marked variation in catheter-tissue contact force during cavotricuspid isthmus ablation using traditional markers of good contact

Saurabh Kumar,1,2 Joseph B. Morton, MBBS, PhD,112 Justin M.S. Lee,1 Michael C.G. Wong,1a Karen Halloran,1 Steven J. Spence,1 Peter M. Kistler,1'3 Jonathan M. Kalman '2

Department of Cardiology & Department of Medicine, The Royal Melbourne Hospital & University of Melbourne, Victoria; Department of Cardiology, Alfred Hospital & Baker IDI, Melbourne, Australia

Background & Objectives: Catheter-tissue contact force (CF) determines radiofrequency (RF) lesion size. We characterized CF during cavotricuspid isthmus (CTI) ablation using traditional markers of "good" contact but blinded to real-time CF measurements.

Methods: 503 lesions in 16 patients using a novel CF-sensing catheter were assessed for average CF (g), force-time integral (FTI, g*s). Experienced operators were instructed to obtain "good" contact based on catheter tip motion, electrogram (EGM) quality/abatement & impedance fall with ablation, whilst remaining blinded to CF measurements. CTI was divided into annular, mid and caval regions for region-specific analysis.

Results: There was significantvariability in CF within andbetween different CTIregions (P<.001). 41% of lesions delivered had average CF <10g despite "good" contact using traditional markers. Lowest CF was at the annulus followed by the mid and the caval CTI (P<.001). Number oflesions with low average CF (<10g) or low FTI (<500g) strongly & linearly correlated with amount of RF time needed to achieve CTI block (r2=.6 to .8). Average CF/FTI was significantly higher in lesions causing persistent CTI block vs. lesions resulting in recovered conduction (P=.001). Each 1gincrease in CF was associatedwith a 16% reduction in risk ofrecovered CTI conduction (P=.01)

Conclusions: Despite significant operator experience, use oftraditional markers of "good" contact resulted in marked variability in real-time CF and nearly half of all lesions delivered with low CF during CTI ablation. Low CF was implicated in longer time to achieve CTI block and increased risk of acute CTI reconnection.

OP 06-6

Remote magnetic navigation for mapping and ablation of atrial fibrillation

WS Teo, JM Fam, SF Liang, M Murni, BY Tan, KL Ho

National Heart Centre, Singapore

Radiofrequency catheter ablation has become an established technique for curative treatment of cardiac arrhythmias. The remote magnetic navigation system (Stereotaxis) involves moving a catheter with a magnetic tip inside a 0.08-0.1 Tesla magnetic field and 3D mapping is done by integrating with the electroanatomical CARTO system. The catheter can then be remotely moved with the operator away from the patient and fluoroscopy.

We report here our experience with the use of the remote magnetic mapping and navigation (Stereotaxis) system from July 2009 to February 2013 for ablation of patients with paroxysmal or persistentAF. There were 137 pts (108 males: 29 females) with a mean age of 54.8 + 10.3 years (range 28-79 years). All patients had isolation of the pulmonary veins as the primary endpoint. Additional SVC ablation was done in 1 pt, left sided SVC in 1 pt, AVNRT SF in 1 pt and atrial tachycardia in 1 pt. CTI ablation was done only when typical atrial flutter was documented prior to or induced during the ablation procedure. The meanprocedure time was 283.1 + 78.6 mins (range 123-600 mins) while the mean fluoroscopy time was 63.3 + 32.7 mins (range 15 - 156 mins). There was reduction in fluoroscopy time from an average of87 mins in 2009 to 35.2 mins in 2013. The procedure time did not show much reduction and was 284.6 mins in 2009 and 270.6 mins in 2013.

There were no major complications. 5 pts (3.6%) had minor complications which included 1 pericardial effusion, 2 pulmonary vein stenosis not requiring further treatment and 2 femoral pseudoaneurysm.

In conclusion, remote magnetic navigation with the Stereotaxis allows successful mapping and ablation of AF with improved safety. It reduces radiation exposure time to the operator and patient.

OP 08-1

OP 08-2

Sequential hybrid approach: results of novel approach in the treatment of longstanding persistent atrial fibrillation

Alan Bulava, JiftHanis, Martin Eisenberger, Vojtech Kurfirst Ales Mokracek

Department o/Cardiology, Department ofCardiac Surgery, Ceske Budejovice Hospital, Czech Republic

Faculty o/Health and Social Studies, University ofSouth Bohemia in Ceske Budejovice, Czech Republic

Background & Objectives: We investigated a "sequential" hybrid approach to test the hypothesis that staged approach in patients with long-standing persistent atrial fibrillation (LSPeAF) may help to achieve complete and durable transmural lesions and translates into higher clinical success.

Methods: Patients with LSPeAF underwent first thoracoscopic epicardial ablation with aim to create circumferential lesions around the ipsilateral pulmonary veins (PVs) using bipolar RF clamps, to complete linear connecting lesions (box lesion and trigone lesion) and to ablate ganglionated plexi. As a second step, a detailed 3D electroanatomical mapping (EAM) ofthe LA using CARTO3 system was performed and all ablation lines were checked and completed, if necessary.

Results: Thirty-five patients (mean age 61±8 years, LA diameter 47±5 mm) were studied. Isolation ofall PVs was found in21 of35 (66%) ofpatients. Bidirectional conduction block across the roof line and across the line connecting the right and left inferior PVs was found in 33% and 60% ofpatients, respectively. Bidirectional conduction block across the anterior mitral isthmus line was feasible to accomplish endocardially in all patients. Additive ablation ofthe LA and RA focal atrial tachycardias (ATs) was necessary in 6 and 5 patients, respectively. Mean procedure and fluoroscopic times reached 149±43 min and 9±4 min, respectively. 90% ofpatients maintained stable SR off antiarrhythmic therapy after at least 6 months following the catheter procedure. Two patients underwent successful redo procedure for recurrent ATs.

Conclusion: Sequential hybrid approach is highly effective in achieving normal SR in patients with LSPeAF.

Clinical success of radiofrequency catheter ablation of atrial fibrillation using two different ablation catheter: a comparison between a conventional irrigated tip ablation catheter vs. contact therapy cool path duo ablation catheter with complex impeda

K. Seidl, C. Pfafferott, M. Kulzer

Klinikum Ingolstadt, Germany

Aim of the study was to evaluate the acute success and complication rate as well as the clinical outcome after 1 year using two different ablation catheters for atrial fibrillation ablation. Methods: In 30 patients (pts) catheter ablation for atrial fibrillation was performed (22 pts with paroxysmal AF, 8 pts with persistent AF). 11 pts ablation was performed with a Contact Therapy Cool Path Duo ablation catheter ( St. Jude Medical, group 1) and in 19 pts ablation was performed with an conventional Therapy Cool Flex irrigated 4 mm tip thermocouple catheter (St. Jude Medical, group 2). The contact system contains circuitry that can make discreet measurements reactance as well as resistance. The term for the composite number is electrical coupling index (ECI). AhighECI means goodtissue contact.

Results: Pts characteristics were comparable in both groups. PVI as the ablation endpoint was achieved in all pts. No significant complication was observed in both groups.

group 1 vs group 2: procedure duration (min): 190 +/- 52 vs 174 +/-54 ns; radiation time (min): 44 +/- 21 vs41 +/- 13 ns; gycm: 8858+/-3680 vs 6206+/-3505 ns; 1 year free ofAF: 81 % vs 79 %

Conclusion: PVI using the electrical coupling index as a measure for tissue contact did not add any additional benefit to the acute and long-term ablation results.

OP 08-3

OP 08-4

Conduction gaps after the first round of circumferential pulmonary vein isolation tend to reconnect in the second procedure even after additional ablation

Kojiro Tanimoto, Kohei Inagawa, Yoshiki Katsumata, Takahiko Nishiyama, Yukinori Ikegami, Takehiro Kimura, Nobuhiro Nishiyama, Kotaro Fukumoto, Yoko Tanimoto, Yoshiyasu Aizawa, Yukihiko Momiyama, Keiichi Fukuda, and Seiji Takatsuki

Tokyo Medical Center, Japan

Background: Insufficient ablation at the first round (1R) of circumferential pulmonary vein isolation (CPVI) is a cause of residual conduction gap (CG) that requires additional ablation, and it may be a predictor ofPV conduction recurrence.

Methods: 19 patients who underwent the second ablation procedure for recurrent atrial tachyarrhythmias were analyzed. At the initial procedure for AF (13 paroxysmal, 6 persistent), all patients underwent CPVI, and LA linear ablations were added up to the operators decision. After 1R of CPVI, additional ablation was applied to the CG on the CPVI line, if PV was not isolated. CG was provoked by ATP at 0min, 30min, and 60min after CPVI. Additional ablation was applied to achieve PV isolation. At the second procedure, CG was analyzed and ablated on the CPVI line. We classified ipsilateral PV perimeter into 8 segments and evaluated the relationship between the segments of CG at the initial procedure and the second procedure.

Results: At the first procedure, additional ablations were applied to CG in 64/304 segments after 1R of CPVI. CG was provoked in 9/304, 22/304 and 2/240 segments at 0min, 30 min and 60 min after CPVI respectively. At the second procedure, CG was observed in 42/304 segments in 14/19 patients. The segments of CG after 1R of CPVI correlated the segments of CG in the secondprocedure (RR=2.12, P=0.04).

Conclusion: CG after 1R ofCPVI is riskfactor for PV reconnection at chronic phase. Sufficient ablation at 1R ofCPVI is important for durable PV isolation.

Esophageal temperature monitoring during pulmonary vein isolation by electrogram-guided point ablation

Shin-ichi Tanigawa, Seiichiro Matsuo, Ken-ichi Tokutake, Ken-ichi

The Jikei University School of Medicine, Japan

Background: Circumferential pulmonary vein (PV) ablation in patients with atrial fibrillation (AF) requires posterior linear ablation region which has to apply the radiofrequency energy delivery the region close to esophagus. Radiofrequency ablation in the posterior left atrium close to esophagus may cause esophageal thermal injury. In this study, we evaluated the esophageal temperature (ET) during PV isolation by non-continuous point ablation method.

Methods: A total of 138 consecutive patients with AF (age 58 years, 121 males) underwent PV isolation with continuous ET monitoring (SensiTherm St Jude Medical, Inc). Radiofrequency energy was segmentally applied with the guidance of circular mapping catheter. Radiofrequency application was ceased when the ET reached 40 degrees C. The endpoint ofPV isolation was to establish the bi-directional conduction block between the PV and left atrium.

Results: All 538 PVs were isolated from the left atrium. No temperature rise (40.0 degrees C) was observed in 30.4 % (42/138) ofpatients. Of 27 patients, esophageal temperature rose at 67 ablation points (left common PV: 20 points (11 patients), left superior PV: 13 points (8 patients), left inferior PV: 33 points (22 patients) and right inferior PV: 1 points (1 patient).

Conclusion: PVs could be isolated without the ET rise in approximately 70 % ofpatients by use ofelectrogram-guided point ablation.

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OP 08-5

Mapping of undistinguishable focal atrial tachycardia post extensive ablation in the atrium: tricks and tips

Weizhu Ju, Bing Yang, Minglong Chen, Hongwu Chen, Fengxiang ZHANG, Jinbo YU, Kejiang Cao

Cardiovascular Division, the First Affiliated Hospital oof Nanjing Medical University, Nanjing, 210029, China

Background: In a special milieu most encountered in the atrium post extensive ablation, the intra-atrial conduction time (IACT) would be significantly prolonged, which will complicate the mapping of focal ATs.

Objective: To delineate the electrophysiological characteristics of focal ATs in this setting and to further investigate the mapping strategy.

Methods: In a 300 patient pool, ten patients were enrolled in the study, with 6 males, average age of 62±6 years. Three dimensional mapping was performed to delineate the activation pattern. The focus nature was validated by the activation mapping, entrainment mapping and subsequent curable ablations. The activation mapping was re-set based on the assumed focal AT.

Results: Totally 10 ATs were mapped. The mean TCL was 306±77ms. The IACT during AT accounted for a mean of 103%±10% of TCL. Two activation patterns were identified based on the relationship between IACT and duration of window of interest, which were named as "pseudo macro reentry" and "chaotic activation", respectively. The former was a focus originated from the vicinity of blocking areas with IACT less than WOI duration (3 cases, 0.97-0.98). The latter mean focal AT exhibiting a disorderly color arrangement with IACT exceeding WOI duration (7 cases, 1.02-1.29). All ATs were terminated by ablation on the original sites.

Conclusions: We delineated a series of focal ATs with significantly prolonged IACT, which was mostly encountered in the situation of post extensive ablation. Two activation patterns were identified, which may facilitate the mapping offocal ATs in this setting.

OP 12-1

OP 12-2

High resolution unipolar mapping with a new multi electrode mapping system predicts infarct scar thickness in a canine infarct model

Anees Thajudeen, Michael Shehata, Brian Stewart, Rohan Dharmakumar, Hiroshi Nakagawa, Xunzhang Wang, Allen M. Amorn, Doron Harlev, Nahan Bennett, Ivan Cokic, Avinash Kali, Ezh Liu, Sumeet S. Chugh, Warren M. Jackman

Cedars Sinai Medical Center, Los Angeles, CA, Rhythmia Medical, Burlington, MA, Heart Rhythm Institute, University of Oklahoma, Oklahoma City, OK, United States oof America

Introduction: During endocardial mapping of chronic infarct scar, we postulated that thicker and thinner areas of scar may be identified by lower and higher unipolar voltage, respectively. The purpose of this study was to use a new ultra high resolution (HR) mapping system (Rhythmia Medical, Boston Scientific) with delayed contrast enhanced MRI (DE MRI) to correlate the unipolar voltage with scar thickness in a canine chronic infarct model.

Methods: Five dogs underwent ligation of LAD, distal to first diagonal. 4.9 ± 0.9 mo after infarction, DE MRI and LV mapping in sinus rhythm were performed. DE MRI was registered to the LV map and examined at depths of 1 mm and 5 mm from the endocardium to establish scar depth. The HR system uses an 8F catheter with basket array (1.6 cm diam) of 8 splines with 64 tiny electrodes (2.5 mm spacing). It generates LV geometry and activation map using all electrograms (EGMs) recorded < 2 mm from LV surface. Endocardial scar was defined as bipolar voltage < 1 mV and normal area as > 2 mV. In areas of low bipolar voltage (endocardial scar), unipolar voltage > 15 mV was postulated to represent endocardial (shallow) scar.

Results: The 4LV maps had 7707±2212 contact EGMs (resolution 2.8 ± 0.7 mm, Fig C). The low voltage area (< 1 mV) on the bipolar voltage map correlated well with the area of scar on the 1 mm deep DE MRI (Figs A & C). The low voltage area (< 15 mV) on the unipolar map correlated with the area of scar on the 5 mm deepDE-MRI (FigsB &E). Higher unipolar voltage (> 15 mV) in areas of low bipolar voltage showed little or no scar at 5 mm depth, consistent with thin scar (probe, Figs C,E).

Conclusion: Higher unipolar voltage in areas of low bipolar voltage may identify thinner areas of

Left stellate ganglion block suppress Ca2+/Calmodulin-dependent protein kinase ii activation and arrhythmia in autoimmune myocarditis model

Hyelim Park, Hyewon Park, Dajeong Lee, Sungha Park, Hui-Na

Yonsei University College of Medicine, South Korea

Background: The autonomic nervous system plays a critical role in the genesis and maintenance of ventricular arrhythmias. This study evaluated the anti-arrhythmogenic effect of left stellate ganglion block (SGB) in experimental autoimmune myocarditis (EAM).

Methods: EAM was produced by the injection of porcine cardiac myosin of 2 mg into footpads, and SGB by injection ofbupivacaine HCl (0.25%, 0.2 mL) to the left SG ofadult Sprague-Dawley rats. Rats were randomly divided into the following four groups: 1) control (control, n=15), 2) EAM (Myo, n=15), 3) EAM and left SGB (MyoNB, n=10), and 4) EAM and oral atenolol administration (MyoBB, n=9).

Results: In Myo group, 4 (27%) out of 15 rats died suddenly at 14 ± 4 days after acute myocarditis, and 5 (45%) of 11 surviving rats had arrhythmia. However, no rat died and had arrhythmia in control and MyoNB groups. Compared with control, QTc interval (161±5 vs. 250±24 ms, p<0.001) were significantly prolonged in Myo group, but not in MyoNB (179±10 ms, p=1.0) and MyoBB group (180 ±15 ms, p=1.0). In Langendorff perfused rat hearts, MyoNB group showed decreased action potential duration (115±7 vs. 148±21ms, p=0.02), the maximum slope of APD restitution curve (0.4±0.1 vs. 1.1±0.1, p<0.001), and inducible ventricular tachycardia (17% vs. 86%, p=0.001) than Myo group. MyoNB group showed significantly decreased inflammatory markers, phosphated Ca2+/calmodulin-dependent protein kinase II (CaMKII), ryanodine receptor type 2 and phospholamban activity than Myo group.

Conclusion: Left SGB suppressed arrhythmia via the prevention ofCaMKII activation in EAM.

OP 12-3

OP 12-4

Expression and regulation of the small-conductance calcium-activated potassium channels in diabetic mouse atria

Fu Yiia, Tian-You Ling 2,3, Tong Lu 2, Xiao-Li Wang2, Win-Kuang Shen, Hon-Chi Lee2

Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China; the Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA; the Department of Cardiology, Rui-Jin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; the Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center New Orleans, LA 70112, USA; and the Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Phoenix, Arizona 85255, USA

Background & Objectives: The small-conductance calcium-activated potassium (SK) channels have been implicated in the pathogenesis of atrial fibrillation (AF) and diabetes mellitus (DM) is a risk factor of AF. We examined the effects ofDM on SK channel expression in mouse atria.

Methods: DM was induced in mice by streptozotocin injection and animals were used after 8 weeks. Expressions of SK channel isoforms were measured by real-time PCR and Western blot analysis. Standard microelectrode techniques were used to measure action potentials in isolated atrial tissues and the effects of apamin (100 pM), an SK channel inhibitor, on action potential duration (APD) and on the development of arrhythmias were determined. Whole-cell SK currents were determined as the apamin-sensitive K+ currents in isolated atrial myocytes.

Results: DM mice had elevated blood glucose (507 mg/dl vs. 140 mg/dl for control, p<0.05, n=11 for both). The SK channel isoform mRNA expressions were not reduced but protein levels of SK2 and SK3 were dramatically down-regulated by 85% and 92% respectively in DM mouse atria (n=3, p<0.05 for both vs. control), while that for SK1 was not altered. Apamin-sensitive SK currents were significantly downregulated in DM atrial myocytes by 2.3- to 8.2-fold over testing potentials of-120 to 40 mV with a holding potential of-60 mV. Control (n=11) and DM (n=8) atria had similar resting potentials (72.0±1.6 mV vs. 72.9±1.5 mV respectively) and APD90s (38.2±1.3 ms vs. 42.2±0.1 ms respectively) but APD50s were significantly longer in DM (17.3±0.3 ms vs 11.2±0.1 ms in control, p=0.02). Exposure to apamin (100 pM) produced significant prolongation of APD90 in controls (43.7±1.3 ms, p=0.002 vs baseline) but had no effect in DM. At baseline, arrhythmias were absent in controls (0/11) but present in 3/11 DM preparations in the form of spontaneous premature beats, early afterdepolarizations and non-sustained tachycardias. With apamin, arrhythmias were recorded in 2/11 control and 6/11 DM preparations (p=0.01 vs control baseline).

Conclusions: SK2 and SK3 channels contribute to the configuration of mouse action potentials and are dramatically downregulated in DM. Inhibition and loss of SK channel function promote the development of arrhythmia in diabetic mouse atria.

The relationship among complex fractionated electrograms, wavebreak, phase singularity, and local dominant frequency in fibrillation wave-dynamics: a modeling comparison study

Minki Hwang1, Yonghyeon Yun, Jae Hyung Park1, Hangsik Shin, Eun Bo Shim2, Hui-Nam Pak1

1Yonsei University Health System, Seoul, South Korea; 2Kangwon National University, Chuncheon, South Korea

Background & Objectives: Although complex fractionated electrogram (CFE) is known to be a target for catheter ablation of fibrillation, its physiological meaning in fibrillation wave-dynamics remains to be clarified. The purpose of this study was to evaluate the spatiotemporal relationships among CFE, wavebreak points (WB), phase singularity points (PS), and local dominant frequency (LDF) during fibrillation by simulation modeling.

Methods: We generated maps of CFE-cycle length (CL; by virtual bipolar recording with electrode distance 1mm), LDF, WB, and PS with 8-14 sec, 14-20 sec, and 20-26 sec fibrillation in 2D homogeneous bidomain cardiac modeling (1000x1000 cells ten Tusscher model). We compared spatiotemporal correlations by dichotomizing each maps into 10x10 lattice zones.

Results:

1. In spatial distribution, WB and PS showed excellent correlation (R=0.963, p<0.001). CFE-CL hadweak correlations with WB (R=0.288, p<0.001), PS (R=0.313, p<0.001), andLDF (R=-0.411, p<0.001). However, LDF didnot show correlation withPS or WB.

2. In the overlaying CFE-CL and PS maps, PSs were mostly distributed at the periphery of low CFE-CL area.

3. Virtual ablation (5% of critical mass) of CFE-CL<100 ms terminated fibrillation at 14.3 sec, and high LDF ablation (5% of critical mass) or changed fibrillation to organized tachycardia, respectively.

Conclusion: In homogeneous 2D fibrillation modeling, CFE-CL was weakly correlated with WB, PS, and LDF, spatiotemporally; however, LDF demonstrated no correlation with either WB or PS. PSs are mostly positioned at the periphery oflow CFE-CL areas, and virtual ablation targeting low CFE-CL regions terminated fibrillation successfully.

OP 12-5

Feasibility, efficacy and safety of percutaneous retrieval of a leadless cardiac pacemaker in an IN VIVO ovine model

J. Sperzel, A. Khairkhahan, D. Ligon, S. Zaltsberg1 -

Kerckhoff Clinic, Department of Cardiology, Bad Nauheim, Germany Nanostim Inc., Sunnyvale, United States of America

Background & Objectives: Leadless pacemaker technology is an emerging method to deliver pacing therapy to the right ventricle offering the benefit of elimination of the surgical pocket and lead. In this study, we examine the feasibility, safety and effectiveness of retrieval of a leadless cardiac pacemaker (LCP) in an in vivo ovine model.

Methods: 10 sheep underwent a percutaneous retrieval procedure with an 18Fr introducer sheath via the right femoral vein at 5 months post implantation. The retrieval catheter was introduced into the RV and positioned at the proximal end of the LCP with a deflectable, steerable catheter under fluoroscopic guidance. All LCP's were retrieved and re-implantation was conducted in 5 of the 10 subjects. The 5 subjects that did not receive re-implantation were euthanized following the procedure and the hearts were examined at necropsy. The 5 subjects that had an LCP reimplantation at the RV apex were assessed angiographically at 6 weeks following re-implantation and then euthanized. The hearts were examined at necropsy.

Results: The LCP was successfully retrieved in all 10 subjects. Implant duration before retrieval was 159-161 days (>5 months). The mean time from retrieval catheter insertion into the 18F introducer and mating to the LCP docking button was 1 min 48 sec (range: 13 sec-3 min 58 sec). The average time from retrieval catheter insertion into the 18F introducer to removal of the LCP and retrieval catheter from the 18F introducer was 2 min 35 sec (range: 1 min to 4 min 4 sec). The average delivery time for re-implantation from delivery catheter insertion to removal from the 18F introducer after implant was 2 min 42 sec (range: 2 min to 3 min). There were no embolizations or dislodgements either during the initial 10-subject retrieval cohort or the subsequent series of 5 reimplanted LCP's. There were no perforations or extrusions of the LCP helix into the pericardial space and the pericardial sac contained normal amounts of serous fluid.

Conclusions: We demonstrate i) the feasibility of retrieval of a leadless pacemaker, ii) efficacy of retrieval and, iii) safety of a novel leadless cardiac pacemaker retrieved from the RV apex.

OP 12-6

Renal sympathetic denervation attenuates the inducibility of ventricular arrhythmia and electrophysiological substrate in dogs with pacing-induced heart failure

Qingyan Zhao

Renmin Hospital of Wuhan University, China

Background: There is an association between renin-angiotensin-aldosterone system (RAAS) and ventricular arrhythmias in heart failure (HF).

Objective: The purpose of the present study is to test the hypothesis that renal artery ablation (RAA) can suppress RAAS and reduce the incidences of ventricular arrhythmias in a canine model ofright ventricular pacing (RVP)-induced HF.

Methods: Dogs were randomized into sham-operated (no RVP), HF (RVP 240bpm) and HFi'VRAA groups. After 3 weeks, echocardiography, electrophysiologic and substrate remodeling assessments of left and right ventricle were performed.

Results: Compared to the baseline, the ventricular dimensions and effective refractory periods (ERPs) increased significantly after 3 weeks in the HF and the HFi'VRAA dogs but not the sham-operated dogs. A greater number of ventricular tachycardias were induced in the HF dogs than the HFi'VRAA dogs. Fibrillation threshold was higher in the HF dogs than the HFiVRAA dogs. The ventricle from HF hearts revealed a large amount of fibrosis, whereas sham-operated and HFi^RAA dogs showed minimal fibrous tissue. Compared with that in sham-operated dogs, levels of BNP, Ang II and TGF-I± in ventricular tissues were increased in HF dogs. However, levels ofthese factors were lower in HFi'VRAA group than that in HF group.

Conclusions: In this HF model, renal sympathetic denervation suppressed the ventricular substrate remodeling and the ventricular arrhythmias vulnerability that was induced by long-term rapid ventricular pacing.

OP 20-1

OP 20-2

TRPC3 channel-dependent regulation of fibroblast proliferation/differentiation in atrial fibrillation

Masahide Harada, Xiaobin Luo, XiaoYan Qi, Artavazd Tadevosyan, Ange Maguy, Balazs Ordog, Kaichiro Kamiya, Itsuo Kodama, Toyoaki Murohara, Ulrich Schotten, David R. Van Wagoner, Dobromir Dobrev, Stanley Nattel

Research Center Montreal Heart Institute, Canada

Background & Objectives: Cardiac fibroblast (FB) proliferation/differentiation contributes to atrial fibrillation (AF)-promoting fibrogenesis. Ca2+-permeable transient receptor potential (TRP) channels modulate cellular function in non-excitable cells. Here, we examined the potential involvement ofTRPC3 in AF-associatedFB activation.

Methods: Left-atrial FBs from AF dogs (600 beats/min atrial-tachypacing, l-week, n=ll) and controls (CTL, n=ll) were used for nonselective cation current (INSC) recording (patch clamp), cell-cycle analysis (flow cytometry) and mRNA/protein expression (qPCR/immunoblot). TRPC3 protein was also measured (immunoblot) in chronic AF (cAF) patient atrial samples (n=8).

Results: AF dogs shortened atrial refractory period by l8%* (BCL l50 ms, *p>0.05 vs. CTL) and prolonged spontaneously maintained AF duration from 26ı8 to 937ı209 s*. In freshly-isolated FBs, INSC sensitive to a TRPC3 selective blocker (pyrazole3), TRPC3 protein expression and extracellular matrix gene (collagen-l) expression increased in AF by 89%*, 64%*, and l2l0%*, respectively. In cultured FBs, the cell number increase-rate, the G2/M cell content (an index of mitosis) and I±-smooth muscle actin protein expression increased in AF by l85%*, 33%* and l54%*, respectively, indicating increased proliferation/differentiation; in vitro treatment with pyrazole3 decreased the fibrotic responses by 78%#, l2%# and 74%#, respectively (#p<0.05 vs. vehicle). Specific TRPC3 knockdown with lentivirus-mediated shRNA reduced FB proliferation by 35%*. Atrial TRPC3 protein also increased in cAF patients vs. CTL (sinus rhythm, n=l0) by ll2%*.

Conclusion: AF increases FB proliferation/differentiation and ECM gene expression by increasing TRPC3 channels. TRPC3 is upregulated in canine and human AF substrate and could be a novel therapeutic target for controlling AF-promoting fibrogenesis.

Receptor for advanced glycation endproducts suppressed arrhythmia by reducing infarct size and apoptosis in myocardial infarction

Hyelim Park, Jueun Hong, Hyewon Park, Hui-Nam Pak, Moon-Hy

Yonsei University College of Medicine, South Korea

Background: The impact of receptor for advanced glycation endproducts (RAGE) blockers on arrhythmogenic effect after myocardial infarction remains unclear. This study evaluated the anti-arrhythmogenic effects ofRAGE in myocardial infarction (MI) model.

Methods: MI was produced by the ligation ofleft anterior descending artery 1 hour in 8-week-old male SpragueaDawley rats. RAGE-siRNA polyplex combined with a polyethyleneimine modified with deoxycholic acid (PE-DA) was delivered to the heart. Rats were randomly divided into the following five groups:

1) control (sham operation, n=10),

2) MI (MI only, n=11),

3) MI-RAGE (MI and RAGE-siRNA injection, n=8) and

4) MI-scRNA (MI and scrambled siRNA injection, n=8).

Results: In MI group, 6 (55%) out of 11 rats died suddenly at 46±14 minutes after acute myocardial infarction. However, no rat died in control and MI-RAGE groups, respectively. The MI-RAGE group had a better survival rate than the MI group (p=0.03). Compared with MI group, MI-RAGE prevented QTc prolongation (143 ± 9, vs. 201 ±21 ms, p<0.001) and arrhythmia (10% vs. 50%, p=0.02). In Langendorff perfused rat hearts, MI-RAGE group showed decreased action potential duration (121±10, vs. 162±60 ms, p=0.001), the maximum slope of APD restitution curve (0.34±0.09 vs. 1.14±0.26, p<0.001), and inducible ventricular tachycardia (0% vs. 71%, p=0.01) than MI group. However, these protective effects were not observed in MI-scRNA group. MI-RAGE group showed significantly reduced infarct size and apoptosis than MI group.

Conclusion: The RAGE-siRNA polyplexes combined with PE-DA suppressed arrhythmia by reducing infarct size and apoptosis in rat MI model.

OP 20-3

OP 20-4

Blockade of NaV1.8 channels in ganglionated plexi influences cardiac conduction and atrial fibrillation inducibility

BZ Qi, Y Wei, SW Chen, GQ Zhou, HL Li JX, LQ Zhao, Y Ding, J Hong, F Zhang, G Chen, J Zhao, SW Liu

Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, China

Background & Objectives: Previous studies suggest that SCN10A/NaV1.8 plays a critical role in cardiac conduction and Atrial fibrillation (AF), but the underlying mechanisms are unclear. The present study was designed to investigate the effects of blocking NaV1.8 channels in cardiac ganglionated plexi on modulating cardiac conduction and AF inducibility in the canine model.

Methods: Thirteen mongrel dogs were randomly enrolled. Right cervical vagal nerve stimulation (VNS) was applied to determine its effects on the sinus rate (SR), ventricular rate (VR) during AF, PR interval, atrial effective refractory period (AERP), and the cumulative window of vulnerability (&amp;amp;Sigma;WOV). NaV1.8 blocker A-803467 (1 mol/0.5 mL per GP, n = 7) or 5% DMSO/95% polyethylene glycol (0.5 mL per GP, n = 6, control) was injected into the anterior right ganglionated plexi (ARGP) and the inferior right ganglionated plexi (IRGP).

Results: The effects of VNS on the SR, VR, PR interval, AERP, and &amp;amp;Sigma;WOV were significantly eliminated at 10min, 35min, and 90min after A-803467 injection. In separate experiments (n = 8), A-803467 blunted the slowing of sinus rate with increasing stimulation voltage of ARGP at 10min after local injection.

Conclusions: Blockade of NaV1.8 channels suppresses the effects of VNS on SR, VR, PR interval, AERP, and AF inducibility, most likely by inhibiting ganglionated plexi function. The underlying mechanism for SCN10A modulating cardiac conduction and AF inducibility may be associatedwiththe regulation ofthe neural activity ofthe cardiac ganglionatedplexi.

An innovative mathematical model with quantum number for rhythm phenomenon and its computer simulation

Mingliang Yang, Jianjun Li, Jian Zhang, Feng Gao, Xianhai Yang,Yutong Feng, Degang Yang

Department of Spinal and Neural Function Reconstruction, School of Rehabilitation Medicine oof Capital Medical University and China Rehabilitation Research Center, Beijing 100068, PR. China

Background & Objectives: The periodic oscillation of intercellular calcium concentration of smooth muscle cells can be induced by norepinephrine. This causes a prolonged vasomotion in vivo. To explain the mechanism ofthe vasomotion, an mathematical model with quantum number was developed by us. The study, by computer simulation, is designed to test the prediction ofthe mathematical model.

Methods: The development environment is based on MyEclipse8.6, and the intermediate software JDK1.5. Using the polar method of Box, Muller, and Marsaglia, the responsive time sequence is pseudorandomly generated and returned by Gaussian function with a mean and a standard deviation variance.

Results: The rhythm of the individual element response depends primarily on its probability density function in time. When its standard deviation was reduced, the responsive rhythm became more uniform and the responsive period approached. When the two subsets were simulated, the subset merger showed a complex pattern. There was a longer excitation period and a shorter refractory period that had a higher incidence of subset fusion. Once the two subsets were merged, the integrated group was usually maintained and the average cycle time could be evaluated in the equality relation. With the saturated stimulation (), both quantum numbers 1 and 2 could be observed in the simulation ofthe group with two subsets.

Conclusion: The computer simulation was consistent with the theoretical prediction. The innovative mathematical model has also potential importance in explaining other rhythmic phenomena in biological systems, such as heart rhythm.

OP 20-5

The role of gap junction in atrial fibrillation caused by atrial stretch

Norihiro Ueda, Takashi Ogawa, Ryoko Niwa, Masatoshi Yamazaki, Haruo Honjo, Kaichiro Kamiya

Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

Background & Objectives: Atrial fibrillation (AF) frequently occurs in patients with heart failure. However, the role ofgapjunction on AF was not fully evaluated.

Methods: The acute atrial stretch model of rabbit was created. A sustained AF (SAF) was induced by a burst of high-frequency stimulation from Bachmann's bundle and effective refractory period (ERP) was measured. Gap junction was enhanced by 100 nM rotigaptide (ZP123) and blocked by 30 pM carbenoxolone.

Results: When atrium was not dilated (0 cm H2O), SAF was not induced. The SAF inducibility was increased with an elevation of intra-atrial pressure. Gap junction enhancer reduced the SAF inducibility and blocker increased. Total conduction time (CT) and conduction patterns of left atrium anterior surface were evaluated by optical mapping. In the absence of gap junction enhancer or blocker, smooth conduction was observed at 0 cm H2O. When intra-atrial pressure was raised to 12 cm H2O, conduction pattern was changed to heterogeneous zig-zag pattern and CT was prolonged. Conduction pattern was not affected by both gap junction enhancer and blocker. Gap junction enhancer shortened CT, in contrast, blocker prolonged CT. ERP was significantly shortened with an increase of intra-atrial pressure. Gap junction enhancer or blocker didnot change the ERP at each intra-atrial pressure.

Conclusion: Gapjunction enhancer inhibited AF causedby atrial stretch, and gapjunction blocker facilitated AF by modification to the conduction velocity of atrium. The regulation ofgapjunction plays an important role in initiation and maintenance of AF.

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OP 20-6

Apamin induces early afterdepolarizations and triggered activity from failing rabbit ventricular myocardium with secondary rise of intracellular calcium

Po-Cheng ChangYu-Cheng Hsieh 1 Chia-Hsiang Hsueh1, James N. Weiss 3 Shien-Fong Lin 1 Peng'Sheng Chen 1

Krannert Institute of Cardiology and Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; 2 Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taoyuan, Taiwan; Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California, United States

Introduction: Heart failure (HF) upregulates small conductance Ca2+ activated apamin sensitive K+ current (Ikas) and downregulates other K+ currents responsible for repolarization. We hypothesize that Ikas is important in preserving repolarization reserve in HF, thereby preventing early afterdepolarization (EADs), triggered activity (TA) and Torsades de pointe (TdP).

Methods: We performed optical mapping studies of Langendorff perfused HF (N=7) and non-failing (N=5) rabbit hearts. Atrioventricular (AV) block was created by cryoablation to allow pacing at slow rates. Optical mapping of membrane potential (Vm) and Ca was performed before and after perfusion with a specific Ikas blocker, apamin (100 nmol/L).

Results: HF (but not normal) ventricles develop a secondary rise in their intracellular Ca2+ (Cai) transient, but do not have spontaneous ventricular arrhythmias at baseline (Fig 1A). Apamin increased APD80 from 252 [95% confidence interval, CI, 212 - 292] ms to 370 [95% CI, 295 - 445] ms at 1000 ms pacing cycle length (p = 0.01) in HF ventricles. EADs occurred in 6 ventricles, premature ventricular beats (PVBs) in 7 ventricles and polymorphic ventricular tachycardia consistent with TdP in 4 ventricles. The earliest activation site of EADs and PVB always occurred at the site with long APD and large amplitude ofthe secondary rise ofCai (Figure 1B). Nifedipine (2 [imol/L) reversedthese effects.

Conclusion: In HF ventricles, apamin induces EADs, TA and TdP from areas with secondary rises of Cai. These findings indicate that Ikas is important in maintaining repolarization reserve and preventing TdP in HF ventricles.

Figure 1 A B

OP 02-1

Predictive potency of big endothelin-1 on response and long-term survival following cardiac resynchronization therapy

Yang Xinwei, Hua Wei, Ding Li-gang, Wang Jing, Liu Zhi-min, Chen Ke-ping, Zhang Shu

Center of Arrhythmia Diagnosis and Treatment, Fuwai Cardiovascular Disease Hospital, CAMS and PUMC, Beijing 100037, China

Background & Objectives: Big ET-1 has known to be a prognostic factor of severe congestive heart failure. The relationship between big ET-1 and response and prognosis in HF patients following CRT remains unclear. To investigate the predictive value of big ET-1 on responsiveness and long-term survival rate after CRT.

Methods: We retrospectively analyzed data of patients underwent CRT implantation in our center from Jan 2009 to Dec 2011. Big ET-1 was measured by ELISA kit within one week before the operation. NYHA functional class, 12-lead ECG and Echocardiography were evaluated at baseline and follow-up. LVEF was measured by using Simpson method. Improvement of LVEF by 5% and decrease in NYHA class> 1 grade was defined as responders; Improvement of LVEF by twice or the absolute value>50% and NYHA class I or II grade was defined as super-responders. Improvement of LVEF < 5% or decrease in NYHA class < 1 grade or the patient died or received heart transplantation was defined as non-responders.

Results: 93 patients (male 64.5%, 60.8 + 11 years old) with median 27 + 11 (12-50) months follow-up were included in this study. There were 34 non-responders, 24 responders and 35 super-responders. Concentration of plasma big ET-1 (fmol/ml) in three groups was 1.2 + 0.9 -0.8 + 0.4 and 0.8 + 0.6 (P=0.022) . During follow-up 13 patients died, 3 patients got heart transplantation, 77 patients remained alive. Difference in concentration of big ET-1 between survival group (0.85 + 0.5) and non-survival and transplant group (1.54 + 1.4) was significant (P=0.001) . Kaplan-Meier survival curve indicated that patients with big ET-1 above the average level (0.95 fmol/ml) had a significant increase in death comparing with patients with big ET-1 lowerthanthe average level (p=0.017).

Conclusions: Plasma big ET-1 was a predictor to response and prognosis after CRT. High concentration of baseline big ET-1 might indicate non-responder and poor prognosis. Plasma big ET-1 could serve as an evaluation item for patient selection for CRT treatment.

Key words: congestive heart failure; cardiac resynchronization; big endothelin-1; responsiveness; prognosis

OP 02-3

Predictive value of plasma N-terminal pro brain natriuretic peptide levels in left atrial spontaneous echo contrast in patients with atrial fibrillation

Kyoung-Im Cho, Tae-Joon Cha, In Kyoung Shim, Jung-Ho Heo, Hyun-Su Kim, and Jae-Woo Lee

Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, South Korea

Background: The present study aimed to investigate the relationship of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with left atrial appendage (LAA) function and the presence ofspontaneous echo contrast (SEC) in patients with non-valvular atrial fibrillation (AF).

Methods: Among 95 patients with non-valvular AF (age 58±9 years) who underwent catheter ablation of AF with transesophageal echocardiography, LAA flow velocities and NT proBNP were comparedbetween 58 patien ts with LA SEC and 37 without SEC. None ofthe patients had a history ofcongestive heart failure.

Results: LAA thrombus was detected in 8 of 58 (14%) patients with SEC. Although there was no significant differences in C-reactive protein (CRP), NT-proBNP levels were markedly higher in patients with LA SEC compared to those without SEC (528.7 pg/ml vs. 233.9 pg/ml, p=0.018). Furthermore, among patients with SEC, NT-proBNP levels were markedly higher in patients with LAA thrombus than in those without LAA thrombus (1038 pg/ml vs. 447.2 pg/ml, p=0.049). NT-proBNP levels were significantly correlated with the presence of SEC (r=0.288, p=0.005), LAA emptying flow velocity (r=-0.349, p=0.001), LA volume index (r=0.547, p<0.001) and the ratio of peak early filling velocity to mitral annulus velocity (E/Ea, r=0.455, p<0.001). Multiple logistic regression analysis showed that logNT-proBNP level was an independent predictor of SEC (odds ratio 1.503, 95% confidence interval 1.084to 2.085; p=0.015).

Conclusion: Elevated plasma NT-proBNP concentrations may be a reliable surrogate marker for the prediction ofLAA dysfunction and the presence of SEC in the atria in patients with AF.

OP 02-2

Decreased endothelial nitric oxide production is more closely related with framigham risk than CHA2DS2-VASc scores in paroxysmal atrial fibrillation

Bonpei Takasel, Masayoshi Nagata

Department of Intensive Care Medicine, National Defence Medical College1, and Iruma Heart Hospital, Japan

Decreased endothelial nitric oxide (NO) production is closely associated with thromboembolic events in patients with paroxysmal atrial fibrillation (PAF). However, in vivo accurate NO measurement is not practical and almost impossible in humans. Brachial artery endothelial flow-mediated vasodilatation (BA-FMD) by using forearm occlusion technique has been reported to reflect mostly NO production. To investigate if BA-FMD-measured NO (simply BA-FMD in this study) can reflect coagulablity in PAF, we measured BA-FMD in 58 patients with PAF (67±12 years old) and compared BA-FMD with Framigham risk scores (FRS) and CHA2DS2-VASc-scores. More than 60% PAF had abnormally low BA-FMD (35/58 patients<6.0%). BA-FMD was measured by UNEXEF18G. BA-FMD more significantly correlated with FRS than CHA2DS2-VASc score (r= -0.45 vs. -0.32, P0.05). BA-FMDs in second and third tertiles of FRS were more significantly impaired than first tertiles of FRS (4.31±1.89, 3.79±3.02 vs. 6.76±2.74%, P<0.05) whereas BA-FMD in CHA2DS2-VASc score>2, that is cut-off value for indication of anti-coagulant therapy, was not different in those of CHA2DS2-VASc score>1 (5.06±2.97 vs. 6.55±2.34%, NS). In conclusions; In PAF patients, not only CHA2DS2-VASc score but FRS might be more important for making decision if the aggressive or moderate anticoagulant therapy is necessary in a certain clinical setting.

OP 02-4

Plasma level of galectin-3 has inverse relationship with transforming growth factor-b and predictive value for clinical recurrence of atrial fibrillation after catheter ablation

JHPark, JS Uhm, B Joung, M-HLee, H-NPak

Yonsei University Health System, South Korea

Background : Galectin-3 is an emerging biomarker which has been studied in relatively heart failure (HF). We hypothesized that galectin-3 plays a role in the pathophysiology of atrial fibrillation (AF) and has a prognostic value after catheter ablation of AF.

Methods: This study included 667 patients who underwent catheter ablation ofAF (75.4% male, 57.4±ll.3 years old, paroxysmal AF (PAF): persistent AF (PeAF) = 472:l95). We evaluated the plasma level of galectin-3 and its relationship with clinical, electrophysiological, and other biomarkers, such as high sensitive C-reactive protein (hsCRP), transforming growth factor (TGF)-I2, tissue inhibitor of metalloproteinase (TIMP)-l, pro-atrial natriuretic peptide (ANP), activated leukocyte cell adhesion molecule (ALCAM), in patients with atrial fibrillation (AF).

Results:

1. The patients with higher plasma level of galectin-3 (¥3.87 ng/mL) were older (58.43±l0.78 vs. 56.4l±ll.38 years, p=0.02l) andhadlower eGFR (76.7±20.0vs. 8l.9±l6.lmL/min) andhigher left atrial peak pressure (22.94±ll.44 vs. 20.58±8.06mmHg, p=0.026). Otherwise, there was no significant difference including the degree of electroanatomical remodeling or ventricular function.

2. The plasma level of galectin-3 have positive linear associations with pro-ANP (B=0.l20, 95%CI 0.0l2~0.228, p=0.029), hsCRP (B=0.022, 95%CI 0.006-0.037, p=0.006), and ALCAM (B=0.008, 95%CI 0.000-0.0l6, p=0.008), but negative linear association with TGF-P (B=-0.027, 95%CI -0.050—0.003, p=0.028).3. During l9.6ıl0.8 months offollow-up, 83.l % ofpatients remained in sinus rhythm (SR). In multivariate Cox regression analysis, the plasma level of galectin-3 was an independent predictor for AF clinical recurrence after RFCA (HR 0.9l0, 95% CI 0.843-0.982, p=0.0l5).

Conclusion: The plasma level of galectin-3 is associated with systemic or local inflammatory markers related to AF, and inverse relationship with TGF-P. Low plasma level of galectin-3 is an independent predictor for clinical recurrence ofAF after catheter ablation.

OP 02-5

QT dispersion: a marker of coronary artery disease and microvascular dysfunction

Betty Raman, Bhupesh Pathik, Rosanna Tavella, Vimal Shekar, Clarence Zhuang, Aimee Som, Ed'Milia Ong, John F Beltrame

University oof Adelaide, Adelaide, Australia

Background & Objectives: Recent reports suggest QTd may correlate with the degree of myocardial ischemia. Increased QT dispersion (QTd), a reflection of heterogenous ventricular repolarization, is thought to be associated with ventricular arrhythmias and sudden cardiac death. We sought to investigate the difference in QT dispersion in patients with (1) Angina and insignificant coronary artery disease (ICAD) (2) Coronary artery disease (CAD) (3) Healthy controls.

Methods: Retrospective analysis was performed of the ECG's belonging to 116 patients from 3 groups: CAD (n=59), ICAD (n=37), Controls (n=20). Obstructive CAD was defined as 3 50% stenosis of the coronary artery. ICAD was defined as stenosis < 50 %. Heart rate, QTc and QTd were calculated. QTd was measured as the difference between maximum and minimum QT intervals on any ofthe 12 leads.

Results:

Characteristic N(%) or Mean ± SD Controls n=20 ICAD n=37 CAD n=59 Controls vs ICAD P Controls vs CAD P CAD vs ICAD P

Age 50 ± 13 57 ± 12 62±10 0.05 <0.01 0.05

Male Gender 9 (45%) 16 (43%) 46 (78%) 1 0.01 <0.01

Heart Rate 60±6 69 ±11 68 ± 13 <0.01 <0.01 0.65

QTc 404 ±56 456 ±68 459 ± 70 <0.01 <0.01 0.86

QTd 56 ± 35 79 ±38 117 ±56 0.02 0.02 <0.01

Conclusion: QTd was greater in CAD compared with ICAD correlating with greater degree of myocardial ischemia. Patients with suspected micro vascular dysfunction or patients with ICAD had greater QTd compared with healthy controls.

OP 02-6

The relationship between the secretion of B-type natriuretic peptide and the effects of several factors in patients with atrial fibrillation

Y. Hayama, K. Kaitani N. Onishi

Tenriyorozu Hospital, Japan

Background: Background: Atrial fibrillation (AF) is associated with elevated levels of B-type natriuretic peptide (BNP). BNP level at coronary sinus (CS-BNP) is considered to be able to reflect the secretion of BNP, because BNP is secreted at ventricles mainly. So we examined the relationship between the secretion of BNP and the effects of several factors in AF patients by measuring of CS-BNP in AF patients who received radiofrequency catheter ablation (RFCA).

Methods: We measured CS-BNP in 55 AF patients who received RFCA [age=60±11years, male=39, paroxysmal AF/persistent AF (PAF/PeAF) =35/20]. The patients had echocardiography, cardiac computed tomography (CT), and blood test before RFCA. Left atrial volume (LAV) was estimatedby CT.

Results: Ln BNP(CS), natural logarithm of CS-BNP, had a significant positive correlation with age (r=0.513, p<0.001), LAV (r=0.658, p<0.001) and peak velocity ofthe early diastolic filling wave (E) at transmitral flow (r=0.271, p=0.04). Ln BNP(CS) had a significant negative correlation with estimated glomerular filtration rate (eGFR) (r=-0.448, p=0.001). Ln BNP(CS) was higher in PeAF patients than PAF patients (p=0.004). Stepwise multivariate linear regression analyses were used to detect independent associations between Ln BNP(CS) and following variables: age, LAV, E, eGFR, type of AF(PAF=0, PeAF=1). Among these variables, age 0=0.379, p<0.001) and LAV (P=0.568, p<0.001) were significant independentpredictors ofLn BNP(CS).

Conclusion: ln AFpatients received RFCA, left atrium enlargement was associated with increase ofthe secretion ofBNP regardless oftype of AF.

OP 01-1

OP 01-2

Electrogram characteristics of quadripolar leads - implications for multipoint pacing

MD Flannery, B Reynolds, TLin, MSwale & D O'Donnell

Arrhythmia Unit, Austin Health, Heidelberg, Melbourne, Australia

Aims: Multipoint pacing (MPP) utilized multipolar leads to pace multiple LV sites in an attempt to improve the response rates to cardiac resynchronization therapy (CRT). This analysis examined the electrogram characteristics of multipolar leads to determine if specific electrogram combinations could be preferentially selected for MPP.

Methods: 41 patients undergoing CRT using St Jude Medical Quadripolar LV leads were assessed 6 week after implantation. Electrical properties were measured using intracardiac electrograms (IEGM), pacing thresholds and compared with anatomical separation. Measurements were recorded from each of the 4 electrodes, during intrinsic rhythm and during RV and LV pacing from each ofthe 4 electrodes.

Results: 38 ofthe 41 patients could be paced from all 4 electrodes. The mean difference in intrinsic electrical activation ofthe 4 electrodes in individual patients was 13ms (3-35ms). With LV pacing from each of the 4 electrodes the maximal difference in electrical timing was 31ms (3-87ms). The maximal intrinsic electrogram separation was recorded between D1 and P4 in 47% of patients and other electrode combinations in 53%. The maximal intrinsic delays and maximal LV paced delays were recorded from the same electrode in 41% of patients

Conclusion: Multipolar leads enable pacing from all electrodes in most cases. Maximal anatomical and electrical separation correlate poorly and maximal intrinsic and paced delays differ in the majority of patients. Pre-specified delivery of MPP will be difficult and individual optimization will usually be required.

Cardiac resynchronization therapy (CRT) - does multiple pacing configurations with the quadripolar LV lead overcome suboptimal lead positioning

VS Prakash, Ravi Narayan, Anupama Hegde, Veeresh Patil Varsha R P.

M S Ramaiah medical college, Bangalore, India

Introduction: Responders to CRT require 1) positioning of LV lead in lateral or posterolateral vein , 2) continued long term biventricular (BiV)capture. Using four independent electrodes, new quadripolar lead (Quad) provides 10 different configurations. This study evaluated whether using this lead overcame limitations of suboptimal lead positioning in reducing nonresponders.

Materials/methods: 94 patients who underwent CRT implantation were included. Group I A) included 55(40 males (M)/15 females (F)) had a bipolar LV lead (BIP) implantation in optimal position, I B) included 20 (14 M, 6 F) in suboptimal location. II A) included 10 patients (8 M, 2 F) underwent Quad lead implant in optimal position and 9 (5 M, 4 F) in suboptimal position. All patients were followed up monthly for atleast 6 months with a 12 lead electrocardiogram and 2 dimensional echo(2DE) and pacing configuration altered 1)primarily to achieve the narrowest QRS 2) secondarily to optimize atrioventricular(AV), interventricular (VV) intervals by 2DE/Doppler and quickopt (algorithm in St. Jude Medical CRT devices).

Results:

Parameters Baseline IA IB II A II B

QRS width(ms) 14ШЗ 12O±1O 112±12 124±S

LV ejection fraction(Simpson's) 2S±15 З6±4 42±S ЗS±S

LV internal dimension(diastole) 72±4 64±З 6S±4 62±4 67±З

NYHA class З±1 11O±14 2±l l±l 2±l

Mitral regurgitation(grade) З±1/4 45±5 З±1/4 2±l/4 З±1/4

% BiV pacing na SS±2 S6±2 96±2 97±2

Conclusion: Pacing with Quad doesn't compensate for suboptimal LV lead positioning which remains most important parameter determining optimal response to CRT though multiple pacing configurations ensure minimal loss ofBiV pacing.

OP 01-3

OP 01-4

Impact of steroid eluting on performance of multiple electrode left ventricular cardiac vein leads in CRT

P. Yang, L. Schotzko, D. Hine, S. Li, andR. McVenes

Cardiac Rhythm Disease Management, Medtronic Inc, United States oof America

Introduction: A steroid-eluting (SE) electrode is known to suppress myocardial inflammation to lower pacing thresholds. Histology studies show that left ventricular cardiac vein (LVCV) lead implant elicits inflammatory response in human. However, little comprehensive information is available on electrical performance ofmultiple SE electrodes LVCV leads in CRT.

Methods: We evaluated electrical performance of quadripolar LVCV lead electrodes with and without SE in a sixteen canine study. Pacing threshold, pacing impedance, and R-wave sensing were collected via the model 2290 Analyzer at weeks 0, 4, 8 and 12. Gross and histopathological examinations ofthe canines were performed at end ofthe study.

In addition, we reviewed and analyzed the long-term pacing performance of Medtronic unipolar and bipolar LVCV lead electrodes with and without SE from human studies to compare the preclinical to these historic clinical results.

Results: The canine study and the human studies showed that SE, surface ratio of cathode to anode and electrode position in CV had major impacts on the long-term pacing performance of Medtronic LVCV leads. The SE tip and ring electrodes predominantly reduced pacing threshold peaking after implant and long-term pacing threshold. Pathohistological examination in the canine study demonstrated suppression ofinflammation surrounding the SE electrodes in CV. The historic human study results ofMedtronic LVCV leads confirmed these finding.

Conclusion: SE on the multiple electrodes ofMedtronic LVCV leads can lower pacing thresholds and improve long-term pacing energy consumption and therefore increase battery longevity of CRT systems in all pacing vectors.

Is the most delayed site the best site for LV lead pacing? insights from optimal LV lead positions

MD Flannery, T Lin, M Swale, D O'Donnell

Arrhythmia Unit, Austin Health, Heidelberg, Melbourne, Australia

Introduction: Whilst left ventricular (LV) leads are conventionally targeted to the site of maximal electromechanical delay, mathematical analyses argue against this. This study assessed the relationship between echocardiography, ECG and intracardiac electrogram (IEGM) parameters by pacing from different electrodes within the targeted LV region.

Methods: Patients undergoing cardiac resynchronization therapy using multipolar leads were enrolled. IEGM's were measured from surface ECG to each LV electrode (QLV) and RV lead electrogram to each LV electrode (Int RV LV). Patients were included ifLV lead was positioned at the target site identified as the most delayed segment on echo, QLV >75% and Int RV-LV > 100ms. Echo measures including dyssynchrony (DI), intracardiac electrograms and ECG's were recorded during pacing from each ofthe LV electrodes.

Results: 21 patients, able to be paced from all 4 electrodes were analysed. In the groups as a whole there was a correlation between increasing intrinsic electrical delay and improvement in DI, in individual patients the correlation was poor. There was no correlation between intrinsic delays and QRS duration or other IEGM measures. The optimal DI was recorded from the most delayed electrode in 11 patients, from the intermediate delayed electrodes in 6 and from the least delayed electrode in 4 patients. The optimal DI was seen with a QLV of 88+-6% and an intrinsic RV to LV delay of117 +- 17ms.

Conclusions: The correlation between pacing at most delayed sites and echocardiographic and electrical parameters isnot uniform. Individual optimization ofleadposition remains important.

OP 01-5

Is left sided single lead DDD pacing feasible?

W.P. Obel1, J. Daniels1, P.J.H.Smeets2, S. Oosthuizen, T. Camps2, V. Rajan

1 Milpark Hospital, Johannesburg, South Africa; 2 Medtronic Bakken Research Center, Maastricht, the Netherlands; Medtronic, South Africa

Introduction: The objective of this study was to investigate the electrical and handling performance of a single pass transvenous LV lead concept with the ability to sense and pace the left atrium (LA) and the left ventricle (LV).

Study Design: A total of 36 patients who were indicated for a CRT-P device were included at two clinical sites in South Africa. The results from five sequential lead prototypes are presented. Evaluation of these prototypes (Model 09008, 09013, 09020 and 13029) in 29 patients has been used as input to the design ofthe final lead (Model 13035) in 7 patients. An Electrophysiology study in 19 patients investigated the viable area distal to Coronary Sinus Ostium for transvenous LA pacing.

Results And Discussion: In total, 36 patients received one ofthe LV-VDD lead prototypes in an acute setting. A satisfactory implant position (adequate atrial sensing together with atrial pacing) in patients with sinus rhythm and LV pacing was accomplished in 26 out of 36 pts. (72%). The data from last 7 patients who received model 13035 lead showed that the electrogram at the atrial electrodes always had an acceptable left atrial sensing between 1.0 and 8.0 V. Unipolar atrial pacing thresholds were generally higher than bipolar, the LV pacing thresholds were satisfactory. The optimal locations from CS OS were a good LA sensing and pacing is possible ranged from 9 to 97 mm.

Conclusions: The electrical performance of the lead and handling data support the feasibility of single pass LV-DDD pacing.

OP 01-6

Targeted lead implantation using a novel left ventricular active fixation lead

Azlan Hussin, Omar Razali, Fredrik Gadler2, Yaariv Khaykin1, Atul Verma, Mark Lazeroms, Kyle Marquard, Raymond Yee

Institut Jantung Negara, Kuala Lumpur, Malaysia; Karolinska Hospital Stockholm, Sweden Southlake Regional Health Centre, Newmarket, Canada; Medtronic Bakken Research Center, Maastricht, The Netherlands, Medtronic, Minneapolis, Minnesota, London Health Sciences Centre, London, United Kingdom

Introduction: Left Ventricular (LV) leads rely on passive fixation for stability. Many times the targeted implant site is not the location where the lead is most stable. We report our experience with a novel active fixation bipolar 4Fr. LV lead that has a small side helix (Model 20066, Medtronic, Inc.) to securely fix the lead in a precise location and improve chronic stability.

Method: Forty patients indicated for CRT were enrolled at four centers in Canada, Sweden, and Malaysia. Standard implant procedures were followed and the implanters were asked to identify a primary target vein and site for the lead tip electrode prior to implanting the model 20066 lead. Once the lead reached a preferable vein location, the lead was fixated and the electrode position confirmed by fluoroscopy.

Results: The Model 20066 lead was successfully implanted in 39 of 40 (97.5%) patients. In 38 out of 40 patients (95.0%) the lead was successfully positioned and fixated in the implanters preselected desired location. The lead was securely fixated in a variety of venous anatomies ranging in size from 4Fr to 15Fr (1.33mm to 5mm) without any dislodgments reported within the first 12 months.

Conclusion: This active fixation technology offers greater flexibility and confidence to place the LV lead precisely in any desired location by assuring lead stability over a range of vein anatomy and locations. The stability of this lead may also lead to a lower re-operation rate when compared to currently available LV leads.

OP 03-1

OP 03-2

Influence of intra-atrial block on the effect of cardiac resynchronization therapy

Qi Sun, Ji Yan

Department of Cardiology, Anhui Province Hospital, Hefei 230001, Anhui Province, China

Background & Aims: Intra-atrial block (IAB) would lower left atrial booster pump function and shorten left ventricular filling time, so it can influence Left Ventricular Function. But there were no reports about correlation between the IAB and the effect of cardiac resynchronization therapy. The purpose of this study was to evaluate the influence of IAB on the effect of cardiac resynchronization therapy.

Methods: Sixty-nine patients with chronic heart failure underwent CRTD were divided into IAB group and non-IAB group according to the P-wave duration and morphology in lead I ' lead aVL or lead V1 of electrocardiogram. IAB group: P-wave duration>120ms or Pd>40ms ; non-IAB group: P-wave duration < 120ms and Pd < 40ms. UCG and DCG were repeated respectively in 1, 3, 6, 12 months after CRTD, whether the patient need to accept a pacemaker optimization guided by echocardiography depended on the patient's heart function.

Results: After 12 months' follow-up, the non-response rate to CRTD (58.8% vs 19.2% ' P=0.003) ,the mortality of 12 months after CRTD (29.4% vs 3.8% ' P=0.008) , the rate of pacemaker optimization guided by echocardiography (41.1% vs 11.5% ' P=0.012) in IAB group, which were obviously higher than those in non-IAB group. Meanwhile, a longer AV/PV delay was needed in the patients in IAB group.

Conclusion: Intra-atrial block increases non-response rate to CRT and the mortality of 12 months after CRTD.

Effects of atrioventricular conduction delay on the outcome of cardiac resynchronization therapy

Ying-Hsiang Lee1, Jia-Hui Wu1, Samuel J. Asirvatham1, Freddy Del Carpio Munoz1, Tracy Webster1, Kelly L. Brooke1, David O. Hodge2, Heather J. Wiste2, Paul A. Friedman1, Yong-Mei Cha1

1 Division of Cardiovascular Diseases and 2 Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota

Background: First-degree atrioventricular (AV) block is a known predictor of increased mortality in the heart failure population. However, its effects in relation to the outcome of cardiac resynchronization therapy (CRT) have not been well examined.

Methods & Results: We retrospectively studied patients who received a CRT defibrillator or pacemaker between January 1, 2002, and September 30, 2010, at Mayo Clinic, Rochester, Minnesota, and who had baseline sinus rhythm with first-degree AV block or normal AV conduction. A standard sensed (100 milliseconds) and paced (130 milliseconds) AV delay was programmed after CRT. Clinical presentations and echocardiography were assessed before and at a median of 6 months after CRT. We identified 403 patients (mean [SD] age, 66.7 [11.7] years) and classified them into 2 groups: normal PR interval (>200 milliseconds) (n=199) and prolonged PR interval (>200 milliseconds) (n=204). The improvements in heart failure functional class (0.7 [0.8] vs 0.5 [0.9], P=.03) and left ventricular ejection fraction (9.4% [12.4%] vs 5.9% [9.5%], P=.007) were greater in the normal PR group than the prolonged PR group. The CRT response rate was more often in the normal PR group than the prolonged PR group after adjusting ischemic cardiomyopathy, left bundle branch block, and use of digitalis (P=.029). However, the adjusted survival were no longer significantly different after CRT (P=.06).

Conclusion: The presence of PR prolongation is associated with less response to CRT in terms of improvement of heart failure symptoms and/or reverse left ventricular remodeling, but it is not a determinant ofsurvival after CRT.

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Cardiac resynchronization therapy (CRT) response and clinical outcomes in NYHA class IV patients: a real world experience

Avinash Verma, Anil Saxena, Aparna Jaswal Niti Chadha, T. S. Kler

Fortis Escorts Heart Institute, India

Background & Objective: Majority ofthe CRT trials have systematically excluded patients in NHYA class IV. CARE-HF, MIRACLE, MUSTIC, CONTAK CD, and PATH-CHF had 6% (n=23), 10% of228, 0, 8% of285, and 12% (n=3) inNYHA ClassIV respectively. We studiedthe efficacy of CRT in NYHA class IV patients.

Method: In a single centre study we prospectively enrolled 105 consecutive patients undergoing CRT device implantation. Primary endpoint was NYHA class change. Hard end points such as cardiac cause re-hospitalizations and death were also recorded.

Results: 105 cases (M/F=71/34) were followed up regularly for mean duration of 10.4±4.7 months. 51% cases were of dilated cardiomyopathy. Majority were in NYHA III (61%) with substantial number in NYHA IV (39%). 20% had atrial fibrillation (either baseline or new-onset). CRT response, defined by NYHA class improvement by at least 1 class, was observed in 69%. 75% of NYHA III and 59% of NYHA IV cases were responders (p=0.088). There were 6 deaths and 34 cardiac cause hospitalizations which was significantly higher in the NYHA IV group (p=0.001).

In a multivariate logistic regression pre-implant NYHA IV was not independently predictive of CRT response (p=0.123). However in Cox regression survival analysis NYHA IV status was associated with increased hazard of cumulative events of hospitalization and death(p=0.000) or hospitalization only(p=0.004).

Conclusion: We conclude that in this study NYHA IV status was associated with equal CRT response rate but more cumulative event rate of death and hospitalizations as compared NYHA III status.

Effect of cardiac resynchronization therapy in heart failure patients with right branch bundle block after ultrasound assessment by tissue doppler imaging

Yi Fu1, Bing Liu1, Feng Wu1, Min Shen1, Dong Liang1, Weijie Li1, Liwen Liu2, Lei Zuo2, Feng Cao1, Haichang Wang1

Department of Cardiovascular Medicine, Department of Ultrasonic Diagnosis, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China

Background: Cardiac resynchronization therapy (CRT) improves mortality of heart failure (HF) patients with QRS duration (QRSd) >120ms, especially in left branch bundle block (LBBB) setting. However, less than 10% of patients with HF and abnormal ventricular conduction were subjected to right branch bundle block (RBBB). Limited data are available in this particular population, and relevant research results are inconsistent.

Objective: To evaluate the effect of CRT in HF patients with RBBB, who presented major inter-and intra-ventricular asynchrony assessed by echocardiography with tissue doppler imaging (TDI).

Methods: All patients with RBBB who underwent the implantation of CRT were included at our center from Jul. 2006 to Jan. 2012. Baseline electrocardiographs (ECG) were analyzed by 2 reviewers, and inter- and intra-ventricular asynchronies were estimated by TDI examination within one week before CRT. Inter-ventricular mechanical delay (IVMD) >40ms and standard deviation of time to peak systolic velocity (Ts-SD) >40ms were presented. Echocardiography markers of cardiac remodeling, 6 minutes walking test (6MWT) and Minnesota living with heart failure questionnaire (LHFQ) were evaluated before and 6 months after CRT implantation.

Results: 195 patients who underwent CRT at our institution were analyzed, of which 14 patients (7.2%) had RBBB on their pre-operation ECG. Ten patients had RBBB plus left fascicular hemi-block (RBBB-LFH), 4 patients had pure RBBB. All patients survived during 6 months' follow-up. The left ventricular ejection fraction (LVEF) and 6MWT were significantly increased (P<0.05), and the left ventricular end-diastolic diameter (LVEDD) was significantly reduced (P<0.05) at 6 months' follow-up compared with baseline. Ten out of 14 patients with RBBB, ofwhom 9 patients with RBBB-LFH and 1 patient with pure RBBB, demonstrated an improvement in LVEF with at least 5% during 6 months' follow-up. Three out of 4 patients with pure RBBB were failed to improve in LVEF.

Conclusion: Patients with RBBB and significant inter- and intra-ventricular mechanical delay may benefit from CRT. Most patients with RBBB benefit from CRT have a coexisting LHB, but patients with pure RBBB rarely benefit from CRT. These observations suggested that patients with heart failure and RBBB plus LHB might be the optimal candidates for CRT when TDI demonstrated that major inter and intra-ventricular delay asynchrony were present. However, this concept remains to be further confirmed by larger population clinical study.

Keyword: Cardiac resynchronization therapy, right branch bundle block, heart failure, echocardiography

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Characterization of mechanical and electrical activation patterns in patients with systolic dysfunction evaluated using a novel non-fluoroscopic 4D navigation system

ArashArya, HediRazavi2, Ole-A. Breithardt, YelenaNabutovsky2, KyungmooRyu, Thomas Gaspar3, Jedrzej Kosiuk1, Charlotte Eitel, Silke John, Gerhard Hindricks1, Christopher Piorkowski

Department of Electrophysiology, University of Leipzig Heart Center, Leipzig, Germany, St. Jude Medical Research, Sylmar, California, USA; Department of Invasive Electrophysiology, University of Dresden Heart Center, Dresden, Germany

Background & Objectives: Optimal LV lead placement and programming in CRT require an understanding of LV mechanical and electrical (M&E) dyssynchrony. We examined simultaneous M&E activation patterns using a novel non-fluoroscopic 4D navigation system (MediGuide™ with EnSite™ Velocity™, St. Jude Medical).

Methods: Patients with systolic dysfunction indicated for VT ablation underwent LV mapping during sinus rhythm with MediGuide. Real-time position of MediGuide sensor-enabled catheters was projected onto pre-recorded cines and used to create motion maps (MMs) from various endocardial points. Local activation time (LAT) and voltage maps were created from the same points and compared with MMs. We defined hypokinesia as maximum inward radial motion <1.5mm, dyskinesia as purely outwardmotion, andscar as voltage <0.5mV.

Results: We performed mapping in three patients (male, 67±13yo, EF 17±3%, QRS 177±35ms, 101±25 map points/patient). In all patients, M&E activation patterns demonstrated high spatial correlation; similar proportion of points had impaired motion and reduced voltage (18.9±2.5% hypokinetic; 8.4±4.1% dyskinetic; 20.1±7.8% scar). An example from one patient (52-yo, ischemic, QRS 140ms, EF 15%) is shown. LAT map (A) demonstrates latest electrical activation along anterior wall (123ms). MM based on time to mechanical activation (B) exhibits latest mechanical activation also along the anterior wall (541ms). Voltage map (C) illustrates scar along inferior, septal, and anteroseptal walls and low voltage (<1.5 mV) around apex. MM (D) exhibits dyskinesia in postero-inferior apex, and hypokinesia along inferior, posterior, and lateral walls.

Conclusion: Characterization of mechanical activation by MediGuide was consistent with electrical activation andmay provide CRT guidance.

Comparison between CRT-D and CRT-P of the elderly patients in saitama medical school international medical center

Yoshifumi Ikeda, Ritsushi Kato, Kazuo Matsumoto, Takahiko Naga

Saitama Medical University International Medical Center, Japan

It is generally known that heart failure (HF) patients have not a little risk of the sudden death in mild to severe stage and efficacy of ICD is similar in older and younger patients. Thus there are many evidences CRT-D is much effective in comparison with CRT-P so far. However elderly patients are at increased risk for inappropriate ICD shocks, because the incidence and prevalence of supraventricular tachyarrhythmias, especially AF, increase with age. In addition, the QOL of patients who experience ICD shocks reduced remarkably. The purpose of this study is to evaluate an effect of CRTD and CRTP in the elderly patients. Methods: 170 CRT (104 CRT-D and 66 CRT-P) were implanted for the HF patients in our institute since 2006 to 2012. Of CRT patients, 30 were over 75 years old (18 CRT-D and 12 CRT-P patients). We retrospectively analyzed the patient's characteristics and outcome, and compare the data between the CRT-P group and CRT-D group. Results: The average period of postoperative monitoring was 28.5months (1-72 months). The average age of CRT-P group was 81.0+/-3.3 years old and CRT-D group were 78.5+/-2.3 years old. The incidence of device-related complications was significantly high in CRT-D group (CRT-P vs CRT-D = 0% vs 33% p=0.03)and the Kaplan meier survival curve did not show a significant difference between two groups (Log rank test p=0.86). Conclusions: The result of our experience indicates that CRT-P can be the important option in comparison with CRT-D in elderly patients.

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Simple protocol of follow-up patients on CRT and its results

Yu. V. Mareev, S.F. Sokolov V.N. Shitov, TA. Malkina, N. Yu. Mironov, V.G. Kiktev, M.A. Saidova, I.R. Grishin, R.R. Mamatkazina, O.V. Sapelnikov, S.P. Golitsyn, R.S. Akchyrin,

Russian cardiology research complex, Russia

Background: There are few works about management of patients after implantation of CRT. Aim ofyour study lookhow simple protocol offollowup can improve management ofpatients.

Methods: We examined 32 patients after 1 week. 1, 3, 6, 12 months after implantation of CRT with use of ECG, 24 hours ambulatory ECG, echocardiogram and analysis of telemetric information from pacemaker.

Results: 7 times ECG found troubleshootings. One time it was dislocation of a lead. 2 times it was elevation threshold of one of the leads, one time it was anodal stimulation, one time it was undersensing of P waves, two times AV delay was as long as AV conduction and this caused pseudofusion beats.

Telemetric analysis shows percent of pacing, episodes of atrial fibrillation and ventricular tachycardia. This information helped to change therapy or pacemaker program in four patients.

24 hours ambulator ECG can improve counts of BV complexes obtained by telemetric control and shows troubleshootings witch ECG were not registered by short ECG recordings. This happened in four patients.

Echocardiogram helped to find patients who need correction of AV delay. Eight patients need this. Echo can reveal thrombus in left ventricle and at pacemakers leads. This happened 4 times in your patients.

Conclusion: Most ofpatients need correction of therapy or change in CRT program. Simple tools like ECG, 24 hours ECG monitor, ECHO, analysis of telemetric data help to find patients who need correction.

A cost analysis of cardiac resynchronization therapy in patients with atrioventricular nodal disease and reduced ejection fraction

Bhupesh Pathik, Thomas Mathew, Fahd Chahadi, Kaye Sutton, Andrew McGavigan

Flinders Medical Centre, Adelaide, Australia

Background & Objectives: Recent studies have suggested that patients with an atrioventricular(AV) nodal pacing indication and reduced ejection fraction(EF) may benefit from cardiac resynchronization therapy(CRT). We sought to investigate the potential incremental cost to a tertiary pacing service of CRT rather than standard pacemakers in these patients.

Methods: Retrospective analysis was performed of devices implanted at a tertiary institution over 8 years. The database was analysed for device type, pacing indication and EF. Cost analysis was performed.

Results: 1751 identified. 172 with CRT excluded. 1280 and 299 received pacemakers and implantable cardioverter defibrillators(ICD) respectively. 192/1280 pacemaker patients had EF<50% and AV nodal disease (142 sinus rhythm(SR), 50 atrial fibrillation(AF)). Ofthese, 55 had EF<35% (25 SR, 30 AF). 11/299 ICD patients had EF<50% and AV nodal disease (5 SR, 6 AF). Ofthese, 9 had EF<35% (5 SR, 4 AF). If patients received CRT rather than standard pacemaker, based on an incremental cost of $4000 per person and EF<50%, this equates to $73500 per year in SR patients or $101500 per year in all patients. In patients with EF<35%, this amounts to $15000 per year in SRpatients or $32000peryear in all patients. Thisrepresents a 1-2% and 5-7% increase in the total pacing budget per year in patents with EF<35% and EF<50% respectively.

Conclusion: Although there is a $4000 incremental cost per person in CRT rather than standard pacemaker in patients with AV nodal disease and reduced EF, overall this represents a modest increase in the total pacing budget.

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Real world assessment of left ventricular lead implant success and complication rates: results from asia-pacific region in the attain success clinical trial

Balbir Singh1, Anil Saxena, Jitendra Singh Makkar1, Ajay Naik4, Sudhir Chandra Sinha5, Tracy Bergemann

Medanta-The Medicity, Gurgaon, India; Fortis Escorts Heart Institute, New Delhi, India; Fortis Escorts, Jaipur, India; Care Institute of Medical Sciences, Ahmedabad, India; Indus Hospital Vzag, India; Medtronic Cardiac Rhythm Disease Management Clinical Research, Mounds View, United States

Background: LV lead implant success rates have historically ranged from 70.5% to 95.5%. Complex coronary venous anatomy can complicate LV lead placement, thus requiring a portfolio of leads and delivery catheters. The Attain Success study is a prospective, non-randomized, multicenter, global study with the primary objectives of assessing the LV lead implant success and complication rates. This analysis focuses on a subset ofpatients from the Asia-Pacific region -China, Hong Kong, India, Malaysia, Pakistan, Singapore, Taiwan and Thailand.

Methods: Patients undergoing CRT implantation were eligible for enrollment. LV lead and catheter implant success and complication rates were assessed after 3 months of follow-up.

Results: A total of 192 patients (62.9±13.1 years, 67% men, and 21% AFib) were enrolled at 16 sites over 14 months with average follow up of 3.2 ± 0.7 months. Of 189 patients attempted with Medtronic delivery catheters, CS cannulation was successful in 188 (99.5%) and the same number had successful LV lead placement. Median implant time was 5 minutes (3-18) for CS cannulation and 12 minutes (3-27.5) for LV lead placement. The overall CRT implant success rate was 186 of 188 attempts (98.9%). Two subjects hadLV lead dislodgments (1.0%), where the LV lead was subsequently repositioned or replaced and the complication resolved.

Conclusions: This is the first analysis from Asia to prospectively evaluate LV lead implantation to date. This subset ofpatients had a 99.5% LV lead implant success rate and two complications using a single family ofleads and delivery catheters.

Effect of baseline QRS interval on cardiac resynchronization therapy (CRT) response: is wider always better?

Avinash Verma, Anil Saxena, Aparna Jaswal, Niti Chadha, T. S. Kler.

Fortis Escorts Heart Institute, Okhla Road, New Delhi, India

Background & Objective: In patients undergoing CRT, we hypothesize that baseline QRS duration will be related to clinical outcomes.

Method: In a single centre study we prospectively enrolled 105 consecutive patients undergoing CRT device implantation. Primary endpoint was NYHA class change. Hard end points such as cardiac cause re-hospitalizations and deaths were also recorded.

Results: 105 cases (M/F=71/34) were followed up regularly for mean duration of 10.4±4.7 months. 51% cases were dilated cardiomyopathy and 49% cases were ischemic cardiomyopathy. Majority were in NYHA class III (61%). However a substantial number of NYHA class IV (39%) cases were also enrolled. 20% had atrial fibrillation (either baseline or new-onset). LBBB was present in 82% whereas 6% and 12% had RBBB and CHB respectively. CRT response, defined by NYHA class improvement by at least 1 class, was observed in 69%. There were 6 deaths and 34 cardiac cause hospitalizations. The mean QRS duration pre-implant was 156ms±18.6ms (range=120ms - 200ms) with 74% having QRS>150ms.

In a multivariate logistic regression QRS duration was not independently predictive of CRT response (p=0.924). Even in univariate analysis QRS<150ms was not related with CRT response (p=0.814). In Cox regression survival analysis QRS duration<150ms was not associated with increased hazard of cumulative events of hospitalization and death (p=0.774) or hospitalization only (p=0.853).

Conclusion: We conclude that in this study involving sicker population (42% NYHA class IV); QRS duration was not related with either CRT response rate or hazard of cumulative end point of hospitalization and death.

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CIED-infections: is the implantation of CIED in the cath lab safe?

K. Seidl, C.Pfafferott, M.Kulzer

Klinikum Ingolstadt, Germany

Background: Infections of CIED as a perioperative complication remain an important problem. Aim ofthe study was to evaluate the incidence of infections of CIEDs implanted in a standard cath lab (CL) vs implanted in a cath lab with an attire protocol similar to an OR.

Methods: We compared in this observational study the CIED infection rates in two different time frames before and after the implementation of a more strict attire hygiene protocol in our CL. In addition teaching about hygiene and infection prevention took place for all medical personnel involved in CIED implantations.

Results: In 2011, 254 implantations were performed (170 pacemakers, 84 ICDs). The average time of operation was 50.6 min for pacemakers and 85.9 min for ICD/CRTs. In 2011 all implantations were done in a CL with routine hygiene standards. The infection rate was 2.4% (6 infections: 3 systemic infections and 3 local infections; 4 infections occurred after a device change, 2 infections occurred after a new implantation; detection of staphylococcus epidermidis in 2 systemic infections). All infected CIEDs had to be explanted. In 2012 we implanted 266 devices (175 pacemakers; 91 ICDs). The median time of operation was 44.1 min for pacemakers and 79.5 min for ICD/CRTs. No single infection occurred.

Conclusion: Ifthe CL is used for implantation of CIEDs, hygiene standards similar to those in the OR should be implemented for all procedures, with carefully teaching ofthe medical staff.

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Risk factor associated device infection, pneumothorax and perforation of heart in 46,506 device implantations: a national population-based study

Chen Tien Hsing, SP. Hung, PR. Chen

Chang Gung Memorial Hospital, Taiwan

Background: Device infection, pneumothorax, and perforation of heart were most serious complications during device implantation.

Objectives: To identify risk factors in Taiwan National Health Research Insurance database will help physician to prevent complication.

Method: We retrieved data ofall C.I.E.D. implantations from 1996 to 2010 in Taiwan NHIRD. C.I.E.D included single, dual-chamber pacemaker, implantable cardioverter defibrillation(ICD), cardiac resynchronized therapy(CRT), and CRT-D. Admission fulfilled criteria with device implantation and cardiac device infection disease code(ICD-9: 99660,99661,9962) defined as device infection. It was considered as pneumothorax if disease coed pneumothorax occurred(ICD-9:5121). Perforation during device implantation defined as if heart repaired operation occurred.

Result: Total 40608 patients with 46506 procedures performed were identified from 1996 to 2010. group. The incidence of device infection, pneumothorax, and perforation of heart were 0.8%, 0.6% and 0.1% respectively. The multivariable-adjusted risk of device infection significantly (P&amp;lt;0.001) increased with gender ([HR]1.69, 95%[CI]1.39-2.06, P&amp;lt;0.001), device replacement([HR]1.71, 95%[CI]1.36-2.15, P&amp;lt;0.001), age, previous infection, and decreased with center volume more than 200 cases/year ([HR]0.54, 95%[CI]0.4-0.73, P&amp;lt;0.001), prophylactic antibiotic ([HR]0.71, 95%[CI]0.51-0.97, P=0.032). The risk of pneumothorax increased with CRT implantation ([HR] 2.71, 95%[CI]1.46-5.04, P=0.002), COPD([HR]1.65, 95%[CI]1.16-2.35, P&amp;lt;0.001), and decreased with device replacement([HR]0.64, 95%[CI]0.47-0.88, P=0.006),diabetes([HR]0.53, 95%[CI]0.39-0.73, P&amp;lt;0.001) ,CKD([HR]0.56, 95%[CI]0.32-0.98, P=0.041). Temporal pacemaker implantation increased risk ofperforation ofheart([HR]2.15, 95%[CI]1.17-3.98,P=0.014)

Conclusion: Even overall risk of device infection, pneumothorax, and perforation of heart were low. Strategies should be taken like prophylactic antibiotic,increased center experience to prevent device infection. Temporal pacemaker implantation increased risks ofperforation ofheart.

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Genome-wide association analysis identifies 3 common variants predisposing to brugada syndrome

Y Mizusawa*, CRBezzina1*, J Bare1*, CA Remme*, JB Gourraud Z3,4,5*! AO Verkerk6, PJ Schwartz '12, P Guieheney13,14, C Antzeleviteh15, E Sehulze-Bahr1, ER Behr1, J Tfelt-Hansen11J1, S Kääb 20:21 , H Watanabe22, M Horie23, N Makila24, WShimizu25, P Froguel D Roden2, VM Christoffels6, M Gessler30, AA Wilde1*, V Probst3,4,5*, JJ Schott34 5*, CDinJ3441* andR Redotf334'*

1 Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; INSERM, UMR1087, l'institut du thorax, Nantes, France ; CNRS, UMR 6291, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France; Heart Failure Research Center, Department of Anatomy, Embryology and Physiology, Academic Medical Center Amsterdam, The Netherlands; Department of Molecular Medicine, University of Pava, Pava, Italy; Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy; Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa; Department of Medicine, University of Cape Town, South Africa; Department of Medicine, University of Stellenbosch, South Africa; Chair of Sudden Death, Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; INSERM, U956, Faculté de Médecine Pierre etMarie Curie, sitePitié-Salpêtriére, Paris, France; UPMC Univ Paris 06, UMR_S956, IFR14, Paris, France; Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, USA; Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine University Hospital, Münster, Germany; Cardiovascular Sciences Research Centre, St George's University of London, London, UK; Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Laboratory oof Molecular Cardiology, University of Copenhagen, Copenhagen, Denmark; Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Medicine I, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians University, Munich, Germany; Munich Heart Alliance, Munich, Germany; Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan; Department of Molecular Physiology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan; Centre National de la Recherche Scientifique (CNRS), UMR 8199, Lille Pasteur Institute, Lille. France; Lille Nord de France University, Lille, France; Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, USA; Developmental Biochemistry, Theodor-Boveri-Institute, Biocenter, University of Wuerzburg, Wuerzburg, Germany * These authors contributed equally to this work

Background: Brugada Syndrome (BrS) is considered as a rare Mendelian disorder with autosomal dominant transmission and is associated with ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death. SCN5A (NaV1.5) mutations are identified in -20% of patients. However, studies in families harboring SCN5A mutations have demonstrated low disease penetrance and in some instances absence of the familial SCN5A mutation in some affected members, which suggests a more complex inheritance model.

Methods: To identify common genetic factors modulating disease risk, we conducted a genome-wide association study on312 individuals withBrS and 1,115 ancestry-matched controls.

Results: Two genomic loci displayed genome-wide significant association. Replication testing on two independent case/control sets from Europe (598/855) and Japan (208/1016) confirmed both associations and revealed a third locus. The cumulative effect of the 3 loci on disease susceptibilitywas large with an odds ratio of21.5inthe presence of>4riskalleles versus < 2.

Two of the three loci had previously been shown to influence ECG conduction parameters in the general population. The third locus encompasses a transcription factor which has not previously been implicated in cardiac electrical function and arrhythmia. Functional studies in knock-out mice for this transcription factor identified differences in expression of NaV1.5, in addition to differences in conduction ofthe cardiac electrical impulse.

Conclusion: Our findings indicate that common genetic variation may have a strong impact on predisposition to BrS and identify a new gene involved in the pathogenesis ofthe disease.

SCN5A mutation is not a risk predictor of recurrent cardiac events for patients with symptomatic brugada syndrome: ten-year follow-up in a large chinese cohort (COBRA_ChiP registry)

Jyh-Ming Jimmy Ju^ng1^, Ching-Yu Chen, Lian-YuLin1, Chia-T Tsai, Yen-Bin Liu, Chih-Chieh Yu, Juey-Jen Hwang, Jien-Jiun Chen, Fu-Chun Chiu, Cho-Kai Wu , Wen-Jone Chen, Fu-Tien Chiang1, Ling-Ping Lai1, Jiunn-Lee Lin1

Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Cardiovascular Center, National Taiwan University Hospital YUn-Lin branch, YUn-Lin county, Taiwan Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan

Background & Objectives: SCN5A mutations are linked to Brugada syndrome (BrS). It is evident that the prognosis of symptomatic BrS patients is much worse than that of asymptomatic BrS patients. The predictive value of SCN5A mutations on prognosis of symptomatic BrS patients alone was never studied prospectively.

Methods: Forty-seven symptomatic BrS patients were consecutively enrolled from 2000 to 2010 (COBRA_ChiP registry). Mutations of SCN5Awere defined as rare, case-only (absent in the 500 healthy subjects without BrS in the Chinese Han population) variants and were validated by functional study. Mutations within 27 translated exons and exon intron boundaries ofthe SCN5A were detected using direct sequencing. These patients were divided into 2 cohorts based on the genotypes of SCN5A after enrollment and clinically assessed every 3 6 months.

Results: The average age at diagnosis of these 47 symptomatic BrS patients was 46 ±14 years. Forty-three patients without SCN5A mutations were identified and 4 contained mutations. The mean follow-up period in BrS patients with SCN5Amutations was 7.8 ±3.7 years and 3.8 ± 3.4 years in those without SCN5A mutation (P = 0.03). The recurrent arrhythmic events were similar in the two groups (log rank test, P=0.07) although the follow-up period was longer in those with SCN5A mutations.

Conclusion: We demonstrated that long-term prognosis of symptomatic BrS patients with/without SCN5A mutations were similar and concluded that SCN5A mutations may be not a predictor of recurrent arrhythmic event in symptomatic BrS patients.

OP 09-3

Variants in SCN5A promoter and regulatory regions associated with various arrhythmia phenotypes including sinus node dysfunction, conduction disease, atrial fibrillation, and idiopathic ventricular fibrillation

Nobue Yagihara1, Hiroshi Watanabel!, Stéphanie Chattel, Phil Barnet, DawoodDurbar5, Seiko Ohno6, Kanae Hasegawa, Ryozo Kuwano4, Richard Redons, Jean-Jacques Schotf, Connie R. Bezzina9, Arthur A.M. Wildee, YukikoNakano11, TakeshiAiba11, Yukiomi Tsuji1, WataruShimizu1, MinoruHorie, Shiro Kamakura, Tohru Minamino, Naoto Endo2, Dan M. Roden5, Naomasa Makita11

department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 2Division of Orthopedic Surgery; 5 Center for the Inter-organ Communication Research; 4Brain Research Institute, Niigata University, Niigata, Japan;5Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan; Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; 8 IINSERM, UMR915, l'institut du thorax, Service de cardiologie Nantes, Nantes, France; Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands;11 Department of Cardiology, Hiroshima University, Hiroshima, Japan; Department oof Molecular Physiology, Nagasaki University Graduate School ofBiomedical Sciences, Nagasaki, Japan; 11 Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan

Background: Mutations in SCN5A have been associated with various arrhythmias, but it is unknown if variants in the promoter and its regulatory regions of SCN5A also modulate the risk of arrhythmias.

Methods: We resequenced the core-promoter and regulatory regions of SCN5A in 1,288 patients with arrhythmia phenotype(s) (atrial fibrillation [AF], n=444; sinus node dysfunction, n=50; conduction disease, n=132; Brugada syndrome, n=573; idiopathic ventricular fibrillation [VF], n=83; early repolarization syndrome, n=6).

Results: We identified mutations in the SCN5A promoter in 33 patients (AF, n=7; sinus node dysfunction, n=2; conduction disease, n=5; Brugada syndrome, n=16; idiopathic VF n=3). Four variants (idiopathic VF, n=2; Brugada syndrome, n=2) were functionary analyzed and each displayed decreased promoter activity than wild-type. In ChIP-Seq analyses, majority ofthe mutations are located at the regions directly bound by the transcription factors that are important for the development and function of heart including TBX3, TBX5, and NKX2-5, and by the chromatin and insulator associated factor CTCF. In the regulatory regions, 3 mutations were identified in patients with AF, and one of the mutations is predicted to disrupt a binding site for a muscle-specific transcriptional-factor TEF1. The regulatory region strongly interacted with human heart nuclear protein blocked by anti-TEF antibody, and the mutation was associated with the decreased regulation of core promoter. Among the common promoter variants, one variant was more frequently identified in patients with AF than controls and decreased promoter activity. Conclusions: Variants in the core-promoter and the regulatory region of SCN5A were associated with various arrhythmia phenotypes.

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OP 09-4

The screening of catechol-o-methyl transferase gene (COMT) is a powerful tool to diagnose susceptibility for long QT-syndrome and for stratification for sudden cardiac death (SCD)

J.Dyczynski

Remede Clinic, Australia

The study takes a fundamental new approach measuring QT-variations time interval, its link to the COMT gene final product activity and Heart Rate Variability (HRV) evaluating their impact on susceptibility for Long QT-Syndrome and risk for SCD.

The genetic expressions of COMT relates to the CLOCK gene governing the circadian rhythms including cardiac ion channels expression and QT duration. The complexity of the biochemical, biophysical, neurological and electromagnetic scenario in stress was measured using HRV, an ECG evidence-based powerful tool reflecting intelligent heart functions, its autonomic modulation andmapping dynamically posttranslational stress scenario.

The study included 105 patients, 39 males and 66 females from 13 to 91 years, average 57.9 years. The heart rate corrected QT-time was measured using Vicardio technology. It displays the combination ECG/ HRV short analysis delivering a colour coded mapping ECG in two minutes. The Cardio Stress Index (CSI) was calculated from 0 to 100% as an algorithm of HRV. The COMT gene and its final product activity was determined by all patients and classified as reduced/ increased activity.

The patients with reduced activity of COMT showed a statistically significant prolonged QT time interval in comparison to patients with the increased COMT activity p&amp;amp;lt;0.001. The majority (91.6%) of patients showed elevated CSI, but no statistic correlation between QT-variations and CSI.

The screening for COMT gene can be used for risk stratification, the susceptibility to develop an acquired Long QT-syndrome and the reduced activity of COMT may be considered as a risk factor in stratification for SCD.

OP 09-5

Genetic background and management of long QT syndrome

Akiko Komori, Naokata Sumitomo, Mami Cho, Hiromi Okuma, Yuriko Abe, Takahiro Nakamura, Junji Fukuhara, Rie Ichikawa, Masaharu Matsumura Hiroshi Kamiyama, Mamoru Ayusawa, Shori Takahashi

Nihon University School of Medicine, Japan

Background & Purpose: We performed this study to know the indication of medication and types ofgenetic background oflong QT syndrome (LQTS).

Methods: From 1987 to 2012, 37 patients (18 males, 19 females; mean age 18.7&plusmn;18.9 years) with LQTS were involved in this study.

Results: By genetic investigation, gene anomaly was detected in 28 patients (76%). The types of LQTS were LQT1 in 20 patients (54%), LQT2 in 6 patients (16%), LQT7 in 2 patients (5%). Beta-blocker was started in 17 patients (46%). Other medication together with beta-blocker was mexiletine in 4 patients, flecainide in 1 patient, and verapamil in 1 patient. Syncope was noted in 8 patients (22%), cardiac arrest in 1 patient, convulsion in 1 patient, near drawing in 1 patient, and palpitation in 1 patient. Benzodiazepine psychoactive medication was used in 2 patients whom emotional excitement had caused syncope. Restriction of exercise was performed in 16 patients (43%).

Conclusion: In this study, most of LQTS has familial history of LQTS. In the 12 families with LQTS, 10 families (83%) revealed genetic anomaly, whereas only a common variant anomaly of KCNH2 gene was found in 1 sporadic LQTS. Some of the patients were treated as epilepsy. Precise check ofthe family and medical history is mandatory to the management ofLQTS.

OP 09-6

Angiotensin II type 1-receptor gene polymorphism, rs5182, is associated with clinical recurrence of atrial fibrillation after radiofrequency catheter ablation

Jaemin Shim, Hee-Sun Mun, Jin Wi, Jae Hyung Park, Jae Sun Uhm, Jong Youn Kim, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak

Yonsei University Health System, South Korea

Background: Previous reports have demonstrated the association between single nucleotide polymorphism (SNP) ofthe angiotensin II type 1-receptor (AT1R) gene and atrial fibrillation (AF). This study evaluated whether AT1R gene variants are associated with the AF recurrence after radiofrequency catheter ablation (RFCA).

Methods: A total of 321 consecutive patients (mean age 56 ±11 years, 77% male) with drug-refractory paroxysmal (70%, n=226) or persistent (30%, n=95) AF who underwent catheter ablation were included. SNP ofthe AT1R gene, rs5182, was genotyped and compared with phenotypes of AF patients. A 24- to 48-hour Holter ECG recording was performed at 3, 6, and 12 months after the ablation.

Results: 1. When we compared the patients with rs5182 variant allele (C, n=153) and those without C allele (n=168), rs5182 variant allele carriers are more likely to have hypertension (53.6% vs. 38.7%, p=0.007). 2. When we compared phenotypes ofthe patients with variant allele and without it, there were no significant differences in baseline characteristics including age, gender, paroxysmal AF, left atrium (LA) size, and medications. However, mean LA voltage was significantly lower inpatients with variant allele (1.25 vs. 1.08 mV, p=0.018). 3. The clinical recurrence (CR) after 3 months of blanking period after RFCA was observed in 31.8% during the median 23 months of follow-up. In Kaplan-Meier survival analysis, variant allele carriers showed worse clinical outcome than wild type carriers (Figure 1, CC+CT vs. TT, Log Rank p=0.04).

Conclusions: Clinical outcome after RFCA of AF might be affected by angiotensin II type 1-receptor gene polymorphism, rs5182, via association with hypertension and electrical remodeling of LA. A functional study that further investigates the relationship between genetic variations of AT1R and electroanatomical remodeling ofLA will be warranted.

Key words: AT1R SNP, atrial fibrillation, catheter ablation, recurrence

OP 11-1

OP 11-2

Cardiac genetic service in management of inherited arrhythmogenic diseases -pioneering experience of a regional referral centre

Ngai-Shing Mok1, Chloe Mak2, Ping-Tim Tsui, Nai-Chung Fong, Kam-Cheong Lee2, Kei-Chiu Tse, Wing-TatPoon2, Ching-Wan Lam4, Albert Chan2

Dept of Medicine & Geriatrics, Princess Margaret Hospital (PMH); Dept. of Pathology, PMH; Dept of Paediatrics & Adol Medicine, PMH; Dept of Pathology, HKU, Hong Kong

Background & Objectives: Cardiac genetic service plays an important role in management of inherited arrhythmogenic diseases (IAD). We reported the initial experience of cardiac genetic service in a regional referral centre for IAD in Hong Kong.

Methods: Clinical and genetic data of probands and their family members with a molecular diagnosis ofIAD who receivedtreatment and/or underwent genetic testing in PMH were reviewed and analysed.

Results: A total of 36 probands (M:F 29:7, mean age 36.7±21.7 years) had molecular diagnosis of IAD. All but one (97%) probands are Chinese. The molecular diagnosis was Brugada syndrome in 12 (SCN5A mutations in 11 and CACNA1C mutation in one); congenital long QT syndrome in eight (LQT1 with KCNQ1 mutations in four, LQT2 with KCNH2 mutations in three and JLN2 with KCNE1 mutation in one); catecholaminergic polymorphic VT with RyR2 mutations in two; hypertrophic cardiomyopathy in ten (MYH7 mutations in four and MYBPC3 mutations in six); arrhythmogenic right ventricular cardiomyopathy with PKP2 mutations in three and dilated cardiomyopathy with LMNA mutation in one. Six probands had history of cardiac arrest, 19 had syncope and 14 had documented VT/VF. Eleven received ICD, two received pacemaker while 18 were on medical treatment. Sixty family members of 18 genotyped probands were screened and 28 found to be mutation carriers. Appropriate treatment and advice on lifestyle modifications were given accordingly.

Conclusion: Genetic testing for IAD is feasible in Hong Kong and should be considered for diagnosis, risk stratification, guiding treatment and genetic counseling of patients and for family screening in IAD.

Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in aborted cardiac arrest syndromes

Saurabh Kumar1'2, Stacey Peters1, Tina Thompson, Natalie Morgan, Ivan Maccicoca3'4, Alison Trainer '3, Dominica Zentner1-, Jonathan M. Kalman1*2, Ingrid Winship23, Jitendra K. Vohra''3

Department of Cardiology, The Royal Melbourne Hospital; Department of Medicine, University of Melbourne; Department oof Genetic Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia

Background & Objectives: Small studies have shown that cardiological screening and genetic evaluation of sudden unexplained death (SUD) and aborted cardiac arrest (ACA) families may uncover a heritable etiology in a significant proportion. We evaluated the yield of a systematic protocol of evaluation of a large, unselected cohort of consecutive autopsy-negative SUD and ACA families.

Methods: We studied 109 consecutive families (411 relatives) referred from the coroner or cardiologist with > 1 autopsy-negative SUD and 52 consecutive ACA victims (91 relatives) referred from cardiologists between 2007 to 2012. A comprehensive cardiological screen was performed followed by targeted genetic evaluation if a clinical phenotype was proven or suspected in evaluated members.

Results: A certain or probable diagnosis was made in 19/109 SUD families (yield 18%), with the majority having long QT syndrome (LQTS, 15%). Diagnosis varied according to proband age with LQT most common in the very young (<20 years) and Brugada syndrome (BrS) in the older age groups (>40 years, P=.03). In contrast, a certain or probable diagnosis was made in 32/52 ACA families (yield 62%), the majority of which were LQTS (21%) and BrS (19%). No clinical or circumstantial factors increased the likelihood of diagnosis in either SCD or ACA families.

Conclusions: In contrast to published experience from smaller series, a comprehensive strategy of cardiological evaluation and targeted genetic testing in over 100 autopsy-negative SUD families was found to be of low diagnostic yield (18%). Diagnostic yield in ACA families was -4 fold higher (62%), consistent with published experience.

OP 11-3

OP 11-4

Identification of a novel de novo mutation associated with PRKAG2 cardiac syndrome and early onset of heart failure

Yang Liu1'2, Rong Bai3, Lin Wang2, Yumei Xue1, Shulin Wu, Gabriel Caceres4, Daniel Barr, Hector Barajas-Martinez, Charles Antzelevitch, Dan Hu

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou, China, 510080; Department of Cardiology, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China, 100029; Department of Molecular Genetics and Experimental Cardiology, Masonic Medical Research Laboratory, Utica, NY, USA, 13501; Department of Chemistry and Biochemistry, Utica College, Utica, NY, USA, 13502

Background: The major structure elements of the AMP-activated protein kinase (AMPK), are a, p, and y sunbunits. Mutations in y2 subunit (PRKAG2), have been associated with a cardiac syndrome including inherited ventricular preexcitation, conduction disorder and hypertrophy mimicking hypertrophic cardiomyopathy. The aim of the present study was to identify PRKAG2 syndrome among patients presenting with left ventricular hypertrophy (LVH).

Methods and Results: Nineteen unrelated subjects with unexplained LVH were clinically and genetically evaluated. Among 4 patients with bradycardia, manifestations of preexcitation were only found in a 19 year old male who also developed congestive heart failure 3 years later. Electrophysiological study of this case, identifiedthe coexistence of an AV accessory pathway and AV conduction defect. Histological analysis of his ventricular tissue isolated by biopsy confirmed excessive glycogen accumulation, prominent myofibrillar disarray and interstitial fibrosis. Direct sequencing of his DNA revealed a heterozygous mutation in PRKAG2 consisting of an A-to-G transition at nucleotide 1453 (c.1453A>G), predicting a substitution of a glutamic acid for lysine at highly-conserved residue 485 (p.Lys485Glu, K485E), which was absent in his unaffected family members and in 215 healthy controls. To assess the role of K485 in the structure and function of the protein, computational modeling calculations and conservation analyses were performed. Electrostatic calculations indicate that K485 forms a salt bridge with the conserved D248 residue in the AMPK p subunit, which is critical for proper regulation of the enzyme, and the K485E mutant disrupts the connection.

Conclusions: Our study identifies a novel de novo PRKAG2 mutation in a young, in which progression of the disease warrants close medical attention. It also underlines the importance of molecular screening of PRKAG2 gene in patients with unexplained LVH, ventricular preexcitation, conduction defect, and/or early onset ofheart failure.

Low P wave amplitude in lead I is protective for clinical recurrence of atrial fibrillation after radiofrequency catheter ablation in patients with ZFHX3 rs2106261 GG genotype

Jae Hyung Park, Jeamin Shim, Minjin Choe, Jae Sun Uhm, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak

Yonsei University Health System, South Korea

Background: ZFHX3 gene single nucleotide polymorphisms in chromosome 16q22 have been reported to be associated with atrial fibrillation (AF). This study evaluated whether ZFHX3 genotypes predict the clinical outcome of radiofrequency catheter ablation (RFCA) for AF, associatedwith electrocardiographic (ECG) characteristics.

Methods: We evaluated the genotypes ofrs2106261 and rs7193343 in 1322 subjects (661 cases: non-valvularAF (75.8% male, 56.8±11.2 years old) vs. 661 age-sex matched control). AmongAF group, we compared the genotypes with clinical and ECG characteristics, electroanatomical remodeling (CT and NavX), and clinical outcome.

Results:

1. The rs2106261 AA genotype (24.51% vs. 9.12%, p<0.001), andrs7193343 AA genotype (51.21% vs. 42.58%, p=0.002) were significantly prevalent in case than in control. The rs7193343 andrs2106261 were strongly associatedto each other (linkage disequilibrium 0.933).

2. The rs2106261 AA genotype was associated with lower frequency of HTN (37.65% vs. 47.70%, p=0.026), or clinical recurrence rate (22.22% vs. 29.06%, p=0.088), and higher P amplitude in lead I (0.094±0.033 mV vs. 0.090±0.031 mV, p=0.187) or posterior LA voltage (1.19±0.96 mV vs. 0.94±0.70 mV, p=0.004) than in GA+GG genotypes.

3. During 22.6±7.5 months follow-up, clinical recurrence rate of AF was 27.4 %, and significantly lower in the rs2106261 AA genotype with lead I P amplitude >0.090 mV (18.89 %) than in GA+GG genotype with lead IP amplitude < 0.090 mV (32.35 %, p=0.016)

Conclusions: ZFHX3 rs2106261 and rs7193343 were prevalent in Korean patients with non-valvular AF. The rs2106261 AA genotype is associated with higher P-wave amplitude in lead I, and protective for clinical recurrence after RFCA.

OP 11-5

Prolonged PR interval has a predictive value for clinical recurrence of atrial fibrillation after radiofrequency catheter ablation in patients with chromosome 4q25 rs2200733 variants

Minjin Choe, Jae Hyung Park, Jae Sun Uhm, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak

Yonsei University Health System, Seoul, South Korea

Background: Single nucleotide polymorphism (SNP) rs2200733 in chromosome 4q25 is known to be associated with atrial fibrillation (AF) and prolonged PR interval in electrocardiography (ECG). Therefore, we explored the predictive values of rs2200733 genotype and PR interval for clinical recurrence of AF after radiofrequency catheter ablation (RFCA).

Methods: We evaluated the frequencies of rs2200733 T-allele in 1322 subjects who underwent RFCA for non-valvular AF (n=661, 56.8711.2 years old, 75.8 % male) and age-sex matched control (n=661). We compared clinical characteristics, ECG findings and rs2200733 genotypes, or clinical recurrence of AF among AF patients.

Results:

1. The rs2200733 T-allele was more commonly found in AF cases than in control (OR 3.712, 95%CI 2.642-5.215, p<0.001).

2. The rs2200733 T-allele was associated with longer PR interval (185.9±32.6 ms vs. 174.8±21.9 ms, p=0.018), longer duration (p=0.018) and higher amplitude (p=0.014) of negative P terminal force in V1 than in CC genotype.

3. During 18.8±8.5 months follow-up, clinical recurrence rate of AF was higher in the rs2200733 T-allele with PR<184 ms (31.5%) than in the T-allele with PR<184 ms (22.7%) or non-variant, CC genotype (16.0%, p=0.018). The rs2200733 T-allele with PR<184 ms was an independent predictor for AF clinical recurrence after RFCA(HR1.412, 95% CI 1.036-1.924, p=0.029).

Conclusion: The rs2200733 T-allele was more frequent in Korean patients with non-valular AF than in control, and associated with prolonged PR interval and negative P-terminal force in V1. The rs2200733 T-allele with PR<184ms hadapredictive value for AFrecurrence after RFCA.

Keywords: Atrial fibrillation, single nucleotide polymorphism, recurrence, electrocardiography, PR interval

OP 11-6

The early experiences of high efficiency mesh like irrigation tip ablation catheter (Coolflex) in atrial fibrillation ablations

Hui-Nam Pak, Boyoung Joung, Junbeum Park, Ki Woon Kang, Jae Sun Uhm, Nam Gyun Kim, Moon-Hyoung Lee

Yonsei University Health System, Seoul, South Korea

Background: We previously reported that the open irritation tip catheter (OITC) improved clinical outcome of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF), compared with conventional catheter. Recently, high efficiency mesh like irrigation tip ablation catheter (Coolflex) was developed to improve the deep tissue ablation. We retrospectively reviewed the 130 early experiences of AF ablation utilizing Coolflex and compared it with OITC ablation.

Methods: Among 1123 patients with AF (male 76.6%, 57.1±11.2 years old, 68.7% Paroxysmal AF [PAF]) who underwent RFCA, we compared 130 ablations with Coolflex and remaining 993 procedures with OITC. We conducted circumferential pulmonary vein isolation (CPVI) and cavotricuspid isthmus block in patients with PAF, and additional linear ablation for posterior box lesion and anterior line in patients with persistent AF (PeAF) as a standard lesion set. Bidirectional block was tested by differential pacing. Additional superior vena cava ablation or complex fractionated atrial electrogram (CFAE) guided ablations were done depending on the operator's decision.

Results:

1. Although there was no significant difference in age, proportion of PAF, CHADS2 score, left atrial (LA) size, ejection fraction, or E/Em between Coolflex group and OITC group in baseline characteristics, the proportion of male was higher in OITC group (77.3%) than in Coolflex group (70.8%, p=0.027).

2. Ablation duration was tended to be shorter in Coolfex group (4888±1209 sec vs. 5026±1671 sec, p=0.066) and bidirectional block rates in anterior line (85.7% vs. 66.6%, p=0.684) and posterior inferior line (70.5% vs. 52.0%, p=0.270) tended to be higher in Coolflex group than in OITC group without statistical significances.

3. Acute procedural complication rates were 3.8% in Coolflex group and 2.2% in OITC group, respectively (p=0.684), and post-RFCA sinus node dysfunction (SND) was significantly higher in Coolflex group (6.2%) than in OITC group (0.2%, p<0.001). All SND in Coolflex group were associated with anterior line and recovered within 2 days.

Conclusion: Coolflex has tendency to improve ablation time or bidirectional block rate of linear ablation compared with OITC in our early experience. However, transient risk of SND is unusually high associated with anterior linear ablation by Coolflex. Follow-up analysis is warrantedto determine the clinical outcome.

Keywords: Atrial fibrillation, Catheter ablation, Coolflex, Sinus node dysfunction