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Lesion gaps assessed by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) are associated with the atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Animal studies have demonstrated that the catheter-contact force (CF), stability, and orientation are strongly associated with lesion formation. However, the impact of those procedural factors on the lesion characteristics associated with AF recurrence has not been well discussed.A total of 30 patients with paroxysmal AF who underwent catheter ablation were retrospectively enrolled. Radiofrequency (RF) applications were performed with 35W for 30s in a point-by-point fashion under esophageal temperature monitoring. The inter-lesion distance was 4mm. The lesions were visualized by LGE-MRI three months post-procedure and assessed by the LGE volume (ml), gap number (GN), and average gap length (AGL [mm]). The gaps were defined as non-enhancement sites of4 mm. The procedural factors including the catheter-CF, stability, and orientation were calculated on the NavX system.Six (20%) of 30 patients had AF recurrences 12 months post-ablation. A univariate analysis demonstrated that the AGL was associated with AF recurrence (hazard ratio [HR]: 1.20, confidence interval [CI]:1.03 - 1.42, p = 0.02). All AF recurrence were found in patients with an AGL of7 mm. The catheter-CF and stability were associated with an AGL of7mm, but not the orientation (CF: HR: 0.62, CI: 0.39-0.97, p=0.038; stability: HR: 0.8, CI: 0.66-0.98, p=0.027).RF ablation with a low CF and poor catheter stability has a potential risk of creating large lesion gaps associated with AF recurrence. This article is protected by copyright. All rights reserved.

Background: Ventricular tachycardia (VT) non-inducibility at the end of ablation is associated with a less likely VT recurrence. However, it is not clear whether we should use VT non-inducibility as a routine end point of VT ablation. The aim of this study was to evaluate VT recurrence in patients in whom VT non-inducibility was not achieved at the end of the RF ablation and the factors attributing to the VT recurrence.Methods: We analyzed 62 patients in whom VT non-inducibility was not achieved at the end of the RF ablation were studied.Results: Over 2 years, 22 (35%) of the cases had VT recurrences. A multivariate analysis showed that an LVEF≥35% (HR:0.19; 95% CI:0.06- 0.49; PConclusion: Even if VT non-inducibility was not achieved, patients with an LVEF≥35% or in whom partial success could be achieved might be prevented from having VT recurrences. The validity of the VT non-inducibility of any VT should be evaluated considering each patient’s background and the results of the procedure.

Background A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. Objective The purpose of this study was to evaluate the LGE area properties of AF rotors in patients with persistent AF. Methods A total of 287 segments in 15 patients with persistent AF (longstanding persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity, and the density was assessed by the entropy (LGE-entropy) and volume ratio of the enhancement voxel (LGE-volume ratio), respectively. Results NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7 and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments, p = 0.001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of 5 patients with AF recurrence, NPAs outside the PV antrum were not ablated in 3 patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. Conclusion AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas. This article is protected by copyright. All rights reserved.

Background Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. Methods Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. Results Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (β = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. Conclusion Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.

BACKGROUND: A computer simulation model has demonstrated that an atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome. METHODS: A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group. RESULTS: Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in 7, AT conversion in 8 patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p=0.023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients but AF did not. CONCLUSIONS: FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response. This article is protected by copyright. All rights reserved.

Background Atrial inflammation plays an important role in initiating atrial fibrosis, which could perpetuate atrial fibrillation (AF). However, the method of visualization of atrial inflammation has not been established. We sought to investigate whether the intensive atrial inflammation caused by cryoballoon ablation (CBA) could be detected by positron emission tomography/ magnetic resonance imaging (PET/MRI) and whether the atrial inflammation could be associated with consequent fibrosis. Methods A total of 10 paroxysmal atrial fibrillation patients after CBA were enrolled. To detect and quantify intensive atrial inflammation, PET/MRI was performed to assess regional 18F‐fluorodeoxyglucose (18F‐FDG) uptake one day after the CBA, and the standardized uptake values (SUV) max were compared between the pulmonary vein (PV) antrum where CBA could be applied and the healthy left atrial (LA) wall where CBA could not be applied. Furthermore, the atrial inflammation one day after the procedure and atrial fibrosis areas one month after the procedure were three‐dimensionally quantified by PET/MRI and late‐gadolinium enhancement magnetic resonance imaging (LGE‐MRI), respectively. Results The mean SUV max at the PV antrum was significantly higher than that on the healthy LA wall (2.12 ± 0.35 vs 1.73 ± 0.30, P = .00021). The volume of the atrial inflammation strongly correlated with that of the atrial fibrosis (r = .94 [.76‐.99], P = .00006). Conclusions The atrial inflammation after CBA could be detected by PET/MRI. CBA‐induced atrial inflammation was strongly associated with consequent lesion maturation., Atrial inflammation plays an important role in initiating atrial fibrosis, which could perpetuate atrial fibrillation (AF).This study demonstrated the feasibility of the PET/MRI visualizing inflammation in the left atrium.

A 41‐year‐old man with persistent atrial fibrillation (AF) underwent radiofrequency (RF) catheter ablation using an online real‐time phase mapping system: ExTRa Mapping. Box isolation could not terminate AF. Subsequently, RF applications on nonpassively activated areas (NPAs), where rotational activations were frequently observed, at the posterior bottom of left atrium outside of box lesion could convert AF to common atrial flutter. Of interest, the NPA near the posterior bottom were located on the patchy fibrotic tissue area assessed by the late‐gadolinium enhancement magnetic resonance imaging. This indicated the possibility of the critical AF rotor meandering through the fibrotic tissue area.

Background Medium‐dose (25 gray) x‐ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x‐ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium‐dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3‐month or 6‐month follow‐up, the animals underwent an open‐chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium‐dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.

Background: We assessed high-frequency stimulation (HFS)-induced changes in the atrial fibrillation (AF) cycle length (AFCL) in the pulmonary vein (PV) after ganglionated plexi (GP) ablation. Methods: Twenty-two patients undergoing catheter ablation for AF were retrospectively enrolled. Sites showing a vagal response (VR) to HFS were defined as GP-positive sites. AFCL was determined in the adjacent PV, distant PV, coronary sinus, and right atrium. Twenty cycles were counted before and after each HFS. After radiofrequency application to the GP site, HFS was repeated. Results: At GP-positive sites (n=57), significant shortening of the AFCL was detected in the adjacent PV (17% shortening, 165±38 to 137±27 ms, p

Background The purpose of this study is to evaluate the rate of perioperative bleeding complications following anticoagulation therapy in patients undergoing implantable electronic device implantation. Methods and results We retrospectively analyzed the data from 161 consecutive patients with new device implants or generator replacement performed between February 2008 and June 2009 in our hospital. Sixty-five (40.3%) patients took warfarin, 55 (34.2%) took antiplatelet therapy, and 16 (9.9%) took dual antiplatelet therapy prior to implantation. Heparin bridging was performed in 7 of 65 patients taking warfarin. Pocket hematoma was observed in 10 (6.2%) patients and device infection was observed in 1 (0.6%) patient. No cases of thromboembolism were observed. There were no complications associated with warfarin ( P =0.19) or antiplatelet therapy ( P =0.69). However, the patients that had undergone heparin bridging were significantly more likely to have complications (3 of 10) ( P =0.005). In multivariate analysis, heparin bridging was the only independent predictor of complications. Conclusion Our study suggests that heparin bridging increases the risk of perioperative bleeding complications in cardiac device implantation.

Functional Block in the Posterior Right Atrium. Introduction: Conduction block in the posterior right atrium (RA) plays an important role in perpetuating atrial flutter (AFL). Although conduction blocks have functional properties, it is not clear how the block line changes with the pacing rate, pacing site, and administration of antiarrhythmic drugs. Methods and Results: Forty patients with typical AFL were enrolled. Pacing (110, 170, 230 ppm) from the coronary sinus ostium (CSo) and low lateral RA was performed. After 1 mg/kg pilsicainide (pure sodium channel blockade) administration, the pacing protocol was repeated. Conduction block was assessed based on a color-coded isopotential map and 20 points of virtual unipolar electrograms in the posterior RA using noncontact mapping. Block line proportion was defined as the percentage of length of the block line between the superior and inferior vena cava. The pacing rate-dependent extension of the block proportion was significant during pacing from both sides (pacing from the CSo: 59 ± 17% at 110 ppm, 69 ± 16% at 230 ppm, P < 0.05; pacing from the low lateral RA: 43 ± 19% at 110 ppm, 55 ± 22% at 230 ppm, P < 0.05). The block line was significantly longer during CSo pacing than during low lateral RA pacing at each rate (all P < 0.05). After pilsicainide administration, the block line extended further. Conclusion: In addition to pacing rate-dependent and site-dependent changes in the block line, pilsicainide further extended the block line length. This phenomenon explains the clinical observation that counterclockwise AFL occurs more frequently than clockwise AFL, and the mechanism of class IC AFL. (J Cardiovasc Electrophysiol, Vol. 23, pp. 827-834, August 2012)

Purpose: To plan, target, and calculate delivered dose in atrioventricular node (AVN) ablation with volume-modulated arc therapy (VMAT) in an intact porcine model. Methods: Seven pigs underwent AVN irradiation, with prescription doses ranging between 25 and 55Gy in a single fraction. Cardiac CT scans were acquired at expiration. Two physicians contoured AVN targets on 10 phases, providing estimates of target motion and inter-physician variability. Treatment planning was conducted on a static phase-averaged CT. The volume designated to receive prescription dose covered the full extent of AVN cardiac motion, expanded by 4mm for setup uncertainty. Optimization limited doses to risk structures according to single-fraction tumor treatment protocols. Orthogonal kV images were used to align bony anatomy at time of treatment. Localization was further refined with respiratory-gated cone-beam CT, and range of cardiac motion was verified under fluoroscopy. Beam delivery was respiratory-gated for expiration with a mean efficiency of 60%. Deformable registration of the 10 cardiac CT phases was used to calculate actual delivered dose for comparison to electro-anatomical and visually evident lesions. Results: The mean [minimum,maximum] amplitude of AVN cardiac motion was LR 2.9 [1.7,3.9]mm, AP 6.6 [4.4,10.4]mm, and SI 5.6 [2.0,9.9]mm. Incorporating cardiac motion into the dose calculation showed the volume receiving full dose was 40–80% of the volume indicated on the static planning image, although the contoured AVN target received full dose in all animals. Initial results suggest the dimensions of the electro-anatomical lesion are correlated with the 40Gy isodose volume. Conclusion: Image-guidance techniques allow for accurate and precise delivery of VMAT for catheter-free arrhythmia ablation. An arsenal of advanced radiation planning, dose optimization, and image-guided delivery techniques was employed to assess and mitigate effects of cardiac and respiratory motion. Feasibility of delivery to the pulmonary veins and left ventricular myocardium will be investigated in future studies. D. Packer Disclosures: Abiomed, Biosense Webster, Inc., Boston Scientific Corp., CardioFocus, Inc., Johnson and Johnson, Excerpta Medica, Ortho-McNeil-Jannsen, Sanofi Aventis, CardioInsight Technologies, InfoBionic, SIEMENS, Medtronic, Inc., CardioDx, Inc., CardioInsight Technologies, FoxP2 Medica, Mediasphere Medical, Wiley-Blackwell, St. Jude Medical, Endosense, Thermedical, EP Advocate LLC, Hansen Medical, American Heart Association, EpiEP, NIH

Purpose: Scanned carbon ion beams might offer a non-invasive alternative treatment for cardiac arrhythmia, which are a major health-burden. We studied the feasibility of this procedure in an animal model. The underlying treatment planning and motion mitigation strategies will be presented. Methods: The study was carried out in 15 pigs, randomly distributed to 3 target groups: atrioventricular node (AVN, 8 animals with 25, 40, and 55 Gy target dose), left ventricular free-wall (LV, 4 animals with 40 Gy) and superior pulmonary vein (SPV, 3 animals with 40 Gy). Breathing motion was suppressed by repeated enforced breathholds at end exhale. Cardiac motion was mitigated by an inhomogeneous rescanning scheme with up to 15 rescans. The treatment planning was performed using the GSI in-house software TRiP4D on cardiac-gated 4DCTs, applying a range-considering ITV based on an extended CTV. For AVN and SPV isotropic 5 mm margins were applied to the CTV, while for the LV 2mm+2% range margins were used. The opposing fields for AVN and LV targets were optimized independently (SFUD), while SPV treatments were optimized as IMPT deliveries, including dose restrictions to the radiosensitive AVN. Results: Median value of D{sub 95} over all rescanning simulations was 99.1% (AVN), 98.0% (SPV)more » and 98.3% (LV) for the CTV and 94.7% (AVN) and 92.7% (SPV) for the PTV, respectively. The median D{sub 5}-D{sub 95} was improved with rescanning compared to unmitigated delivery from 13.3 to 6.5% (CTV) and from 23.4 to 11.6% (PTV). ICRP dose limits for aorta, trachea, esophagus and skin were respected. The maximal dose in the coronary arteries was limited to 30 Gy. Conclusion: We demonstrated the feasibility of a homogeneous dose delivery to different cardiac structures in a porcine model using a time-optimized inhomogeneous rescanning scheme. The presented treatment planning strategies were applied in a pig study with the analysis ongoing. Funding: This work was supported in part by the Helmholtz Association, the American Heart Association Midwest Affiliate Postdoctoral Fellowship Grant, the Mayo Clinic Foundation, and the Goldsmith Foundation.« less

Mitral isthmus (MI) ablation is challenging. Blood flow in the CS and circumflex artery (LCx) may act as a heat sink and reduce the efficacy of radiofrequency ablation. Ablation in the CS also has the risk of injury to the LCx. We have reported to be able to visualize the precise anatomical characteristics between CS and LCx on MI obtained by MDCT. The aim of this study was to evaluate usefulness of MDCT guided MI ablation. Methods: Twenty patients (14 males, 61±11 y) whose CS and LCx images could be obtained simultaneously by MDCT were included in this study. We performed MI ablation between LIPV and the mitral annulus. The strategy for MDCT guided MI ablation were 1. MI line was designed just below LAA, 2. In case of LCx below CS, MI line was designed proximal the crossing point of LCX and CS, and 3. If LCX is presence on MI, MI line designed more laterally on comparatively peripheral LCX. Irrigated-tip catheters were used during MI ablation with the following settings: endocardial surface (maximum power: 40 W); CS (maximum power: 20 W). Results: The MI was blocked in 94.5% (19/20) of patients with 594±293 seconds of radiofrequency application. The epicardial ablation inside the CS was required in 45% (9/20) patients. No complications occurred. Conclusion: The MDCT guided MI ablation resulted in a high success rate of MI block without complications.

Purpose: Non-pulmonary vein (PV) foci are sometimes difficult to identify and eliminate. This study aimed to characterize non-PV foci using the EnSite array or NavX system. Methods and Results: 138 patients with atrial fibrillation (AF) were included. All patients underwent PV isolation and additional ablation of non-PV foci if present. We revealed 17 non-PV foci in 15 patients. Nine foci induced AF and 8 foci showed more than 3 beats firing. Eight foci occurred spontaneously and the others were induced by low dose of isoproterenol (0.5γ, n=1) or high dose (≥10γ, n=8). The non-PV foci were distributed in the SVC (n=9, 50%), left atrium (LA) (n=5, 29%; 2 anterior wall, interatrial septum, appendage and mitral annulus), right atrium (RA) (n=3, 18%; lateral, posterolateral, anterolateral). 2nd session ablation was required in 36 patients (26%) and 31 patients had LA-PV reconnection. We revealed 16 non-PV foci in 14 patients in the 2nd session. Only one patient had non-PV foci recurrence from SVC. The others were firing at the different site from 1st session. Conclusion: The site of Non-PV foci was half in the SVC and each quarter in the LA and RA. The distribution of LA foci was various while RA foci existed near lateral side. If non-PV foci were successfully terminated, other foci may cause the recurrence of atrial fibrillation.

AF termination was often occurred during ganglionated plexi (GP) ablation. The purpose of this study was to characterize the electrograms at the site of AF termination by GP ablation. Method: Eighteen patients with AF termination by GP ablation were studied. In case of patients with sinus rhythm, AF was induced by rapid atrial pacing. The sites where vagal response was evoked by high-frequency stimulation were determined as GP sites and ablated. The bipolar electrograms were recorded in a 4.5-s window before the RF delivery. Result: AF termination was seen at superior left GP ablation in 3 patients, anterior right in 2 patients, inferior left in 6 patients, and inferior right (in 7 patients). Continuous electrical activity (CEA) was seen at the termination site in 16 (89%) patients. Other 2 patients without CEA, cycle length was 207±18 ms. The maximum duration of CEA was 1.8±0.3 of 4.5 sec. There were 2 patients with only CEA at the termination sites during all recording period. The maximum amplitude of CEA in 16 patients was 0.58±0.99 mV. Conclusion: The electrograms at the sites of AF termination by GP ablation show mainly transient CEA with relatively low voltage.

The Ganglionated Plexi (GP) and complex fractionated atrial electrograms (CFAE) play the important role as the perpetuator of atrial fibrillation (AF). GP ablation is known as alternative procedure for AF. The aim of this study was to evaluate the contrast between the area of the GP and CFAE. Method: Ten consecutive patients with AF were studied. For patients with sinus rhythm, AF was induced by rapid atrial pacing. The geometry of Left atrium (LA) was reconstructed with electroanatomical mapping system (CARTO XP). Bipolar electrograms recorded during 2.5 second were analyzed using CFAE software module. The algorism was customized to demonstrate the classification as follows in Interval confidence level (ICL) map. Sites with continuous or transient fractionated atrial potentials were colored red. Sites with irregular amplitude, polarity, cycle length but not rapid were colored green. Sites with slow organized atrial potential were purple. The sites where vagal response was evoked by high-frequency stimulation were identified as GP sites and marked on the geometry. Result: A total of 1,107 points were taken in LA. Among a total of 197 GP points, 139 (77.2%) points were in colored red and categorized as in CFAE area. GP points in colored purple categorized as in slow organized area were only 4 points (2.3%). Conclusion: The Ganglionated Plexi is strongly related to CFAE.

The antifibrillatory effect of ganglionated plexi (GP) ablation is not well established. The aim of this study was to evaluate the factors associated with termination during GP ablation in patient with paroxysmal AF. Methods: Thirty-two consecutive paroxysmal AF patients (age 61±10 years, 25 male) who underwent the selective GP ablation guided by high frequency stimulation (HFS) were enrolled in this study. The five major left atrial GP were localized by delivering HFS (20 Hz, 20 V, 10 ms pulse width). Radiofrequency current is then applied to that site to eliminate the parasympathetic response. We ablated GP first, and antrum PV electrical isolation (APVI) adjunctively. We measured cycle length (CL) in each PV, left atrial appendage (LAA), coronary sinus (CS), RA, during AF before any ablation. We investigated the termination of AF in relation with GP ablation. Results: AF was induced and sustained in 29 patients. AF terminated during GP ablation in 14 patients (48%), during APVI in 6 patients (21%). Two of 3 patients without sustained AF had SVC foci. The LAA and CS AFCL (142±22 ms, 138±19 ms) in 9 patients without termination were shorter than that in 20 patients with termination (170±33 ms, 171±27 ms, p