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Background: Atrial fibrosis and inflammation play important roles in perpetuating and initiating atrial fibrillation (AF). Although the fibrotic area can be visualized as a delayed enhancement area on late gadolinium enhancement magnetic resonance imaging (LGE-MRI), atrial inflammation has not yet been visualized on any imaging modality. We describe the protocol for a feasibility study to visualize atrial inflammation on positron emission tomography/MRI (PET/MRI). Methods and Results: This is a single-arm, prospective, open-label proof-of concept trial, involving AF patients after cryoballoon ablation (CBA). A total of 30 paroxysmal AF patients will be enrolled and undergo simultaneous PET/MRI for the assessment of regional 18F-fluorodeoxyglucose (18F-FDG) uptake 1 day after the CBA. Furthermore, LGE-MRI will be performed before CBA, and at 1 and 4 weeks after assessing the regional LGE area. The main outcome measures will be (1) the feasibility of imaging inflammation in the left atrium on PET/MRI; and (2) the safety of the intervention. Conclusions: There are few data on the visualization of atrial inflammation using PET/MRI. Establishing the visualization methodology will contribute to elucidating the fundamental histopathologic findings of the progress to fibrosis, and to the planning and execution of a larger definitive trial to test the usefulness of PET/MRI.

Background: Some of atrial fibrillation (AF) drivers are found in lesser late-gadolinium enhancement (LGE) areas, as well as heterogenous ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in lesser LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping). Lesser LGE areas were defined as areas with a volume ratio of the enhancement voxel of

Atrial tachycardia (AT) in the right atrium often occurs following open‐heart surgery. Catheter ablation for these AT is challenging and can lead to unintended conduction block. We performed late‐gadolinium enhancement magnetic resonance imaging (LGE‐MRI) prior to catheter ablation and predicted wavefront propagation during SR as well as the slow conduction zone during tachycardia. LGE‐MRI may assist predicting the conduction disturbance and reducing the risk of unexpected sinus exit block., Late‐gadolinium enhancement magnetic resonance imaging (LGE‐MRI) prior to catheter ablation of postoperative AT in RA can predict wavefront propagation during sinus rhythm as well as the slow conduction zone during tachycardia. It could reduce the risk of unexpected sinus exit block and PM implantation.

A 61‐year‐old female with 50 000 ventricular premature contractions and a reduced left ventricular ejection fraction of 35% was referred to our center. Although the origin was considered to originate from the junction between the left and right coronary cusp, a single radiofrequency application above the aortic sinus cusp could eliminate it. LGE‐MRI was able to reveal the exact location of the single RF lesion.

Background: Coronary artery spasms (CASs), which can cause angina attacks and sudden death, have been recently reported during catheter ablation. The aim of the present study was to report the incidence, characteristics, and prognosis of CASs related to atrial fibrillation (AF) ablation procedures. Methods and Results: The AF ablation records of 22,232 patients treated in 15 Japanese hospitals were reviewed. CASs associated with AF ablation occurred in 42 of 22,232 patients (0.19%). CASs occurred during ablation energy applications in 21 patients (50%). CASs also occurred before ablation in 9 patients (21%) and after ablation in 12 patients (29%). The initial change in the electrocardiogram was ST-segment elevation in the inferior leads in 33 patients (79%). Emergency coronary angiography revealed coronary artery stenosis and occlusions, which were relieved by nitrate administration. No air bubbles were observed. A comparison of the incidence of CASs during pulmonary vein isolation between the different ablation energy sources revealed a significantly higher incidence with cryoballoon ablation (11/3,288; 0.34%) than with radiofrequency catheter, hot balloon, or laser balloon ablation (8/18,596 [0.04%], 0/237 [0%], and 0/111 [0%], respectively; P

Introduction: The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. Methods and Results: We investigated 2737 consecutive patients (25.6% female, mean age 63.4 ± 10.3 years) who underwent a first catheter ablation for AF from the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 25.2 months, 2070 (75.6%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 122 (4.5%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.7 per 100 person-years) compared with the AF recurrence group (3.2 per 100 person-years; P = 0.001). The multivariate analysis revealed that freedom from AF (hazard ratio 0.57; 95% confidence interval 0.39–0.83; P = 0.003) was independently associated with the incidence of the composite event.¬¬ Conclusion: In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Background: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy fibrotic tissue 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 fibrotic tissue 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). Atrial fibrosis was detected by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI), and the fibrotic heterogeneity and density were 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. Conclusion: AF rotors are mostly distributed in relatively weak and much more heterogenous fibrotic tissue.

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA

Background: Computer simulation model demonstrated that atrial fibrillation (AF) driver attached to the patchy 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 is to investigate whether radiofrequency (RF) application on the patchy LGE site (PLS) could terminate AF or convert to atrial tachycardia (AT) and improve the rhythm outcome. Methods: A total of 31consecutive persistent AF patients with PLS were enrolled (PLS ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). AF direct termination or AT conversion during RF application on the PLS were defined as favorable response. The rhythm outcome was compared between the PLS ablation group and the propensity matched conventional ablation group. Results: Favorable response was found in 15 (48%) of 31 patients (AF termination in 7, AT conversion in 8 patients). AF recurrence at 12 months follow-up was significantly less in the PLS group as compared to the control group (4 (13%) of 31 patients vs. 11 (35%) of 31 patients, log-rank p = 0.019). In patients with favorable response, AT recurred in 1 (7%) of 15 patients but AF. Conclusions: The PLS ablation could terminate AF or convert to AT in half of the patients and improve the rhythm outcome as compared to the conventional ablation. No AF recurrence was documented in patients with a favorable response.

Background Pulmonary vein isolation (PVI) lesions after cryoballoon ablation (CBA) are characterized as a wider and more continuous than that after conventional radiofrequency catheter ablation (RFCA) without the contact force (CF)-sensing technology. However, the impact on the lesion characteristics of ablation with a CF-sensing catheter has not been well discussed. We sought to assess the lesions using late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) and to compare the differences between the two groups (CB group vs. RF group). Methods A total of 30 consecutive patients who underwent PVI were enrolled (CB group, 18; RF group, 12). The RF applications were delivered with a target lesion size index (LSI) of 5. The PVI lesions were assessed by LGE-MRI 3 months after the PVI. The region around the PV was divided into eight segments: roof, anterior-superior, anterior carina, anterior inferior, bottom, posterior inferior, posterior carina, and posterior superior segment. The lesion width and visual gap of each segment were compared between the two groups. The visual gaps were defined as no-enhancement site of >4 mm. Results The mean LSI was 4.7 ± 0.7. The lesion width was significantly wider but the visual gaps were more frequently documented at the bottom segment of right PV in the CBA group (lesion width: 8.1 ± 2.2 vs. 6.3 ± 2.2 mm; p = .032; visual gap at the bottom segment or right PV: 39% vs. 0%; p = .016). Conclusions The PVI lesion was wider after CBA, while the visual gaps were fewer after RFCA with a CF-sensing catheter.

Noninvasive ablation of cardiac arrhythmia by scanned particle radiotherapy is highly promising, but especially challenging due to cardiac and respiratory motion. Irradiations for catheter-free ablation in intact pigs were carried out at the GSI Helmholtz Center in Darmstadt using scanned carbon ions. Here, we present real-time electrocardiogram (ECG) data to estimate time-resolved (4D) delivered dose. For 11 animals, surface ECGs and temporal structure of beam delivery were acquired during irradiation. R waves were automatically detected from surface ECGs. Pre-treatment ECG-triggered 4D-CT phases were synchronized to the R-R interval. 4D-dose calculation was performed using GSI's in-house 4D treatment planning system. Resulting dose distributions were assessed with respect to coverage (D95 and V95), heterogeneity (HI = D5-D95) and normal tissue exposure. Final results shown here were performed offline, but first calculations were started shortly after irradiation The D95 for TV and PTV was above 95% for 10 and 8 out of 11 animals, respectively. HI was reduced for PTV versus TV volumes, especially for some of the animals targeted at the atrioventricular junction, indicating residual interplay effects due to cardiac motion. Risk structure exposure was comparable to static and 4D treatment planning simulations. ECG-based 4D-dose reconstruction is technically feasible in a patient treatment-like setting. Further development of the presented approach, such as real-time dose calculation, may contribute to safe, successful treatments using scanned ion beams for cardiac arrhythmia ablation.

Background The safety of discontinuing oral anticoagulant (OAC) after ablation for atrial fibrillation (AF) in Japanese patients has not been clarified.Methods and Results:A study based on the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) was conducted. Data were collected from 3,451 consecutive patients (74.1% men; age, 63.3±10.3 years) who had undergone AF ablation at any of 24 cardiovascular centers in Japan between August 2011 and July 2017. During a 20.7-month follow-up period, OAC therapy was discontinued in 1,836 (53.2%) patients; 51 patients (1.5%) suffered a stroke/transient ischemic attack (TIA), 71 (2.1%) suffered major bleeding, and 36 (1.0%) died. Patients in whom OAC therapy was discontinued were significantly younger than those in whom OACs were continued, and their CHA2DS2-VASc scores were significantly lower. The incidences of stroke/TIA, major bleeding, and death were significantly lower among these patients. Upon multivariate adjustment, stroke events were independently associated with relatively high baseline CHA2DS2-VASc scores but not with OAC status. Conclusions Although the incidences of stroke/TIA, major bleeding, and death were relatively low among patients for whom OAC therapy was discontinued, stroke/TIA occurrence was strongly associated with a high baseline stroke risk rather than with OAC status. Thus, discontinuation of OAC therapy requires careful consideration, especially in patients with a high baseline stroke risk.

Introduction The ablation index (AI) and lesion size index (LSI) are novel markers for predicting the ablation lesion quality, however, collateral damage is still a concern. This study aimed to compare the lesion characteristics and tissue temperature profiles between 20 W (20 Ws) and 40 W (40 Ws) ablation settings under the same AI and LSI. Methods An ex vivo model consisting of swine myocardium (5-6 mm thickness) in a circulating, warmed saline bath was used. Twenty-one tissue temperature electrodes were used. Radiofrequency applications with different power settings were performed with a 10 to 12 g contact force until the AI and LSI reached 350 and 4.5, respectively. Results A total of 120 radiofrequency (RF) applications and 2520 tissue temperature profiles were analyzed. The speed of the tissue temperature rise with 40 Ws was significantly faster than that with 20 Ws. However, the maximum tissue temperature did not significantly differ between 20 and 40 Ws with the same AI (44.6°C ± 3.9°C vs 45.1°C ± 6.4°C, P = .73), and was significantly lower for 40 Ws with the same LSI (42.8°C ± 3.4°C vs 40.0°C ± 3.4°C, P = .003). For both the AI and LSI, the number of electrodes exhibiting high temperatures (≥39°C) was significantly larger and the duration of high tissue temperatures was significantly longer with 20 Ws. The thermal latency with 40 Ws was greater. Conclusions Although the targeted AI and LSI were the same for both 20 and 40 Ws, the tissue temperature profiles differed greatly depending on the RF power setting. A high power setting based on the AI and LSI may reduce the collateral thermal damage.

Background Spontaneous coronary artery rupture (SCAR) is an extremely rare but life-threatening state. The aetiology and the pathologic findings remain to be fully elucidated. Case summary A 62-year-old woman, who had been on haemodialysis for 27 years, presented with chest discomfort worsening on deep inspiration that had been ongoing for the past 2 weeks. An echocardiogram and computed tomography showed diffuse pericardial fluid. ST elevation in the broad leads, especially in leads I, II, and aVF, and increased C-reactive peptide and Troponin I levels suggested pericarditis. The patient initially had a stable course with no medications. The chest symptoms disappeared and her vital signs were stable. On Day 13 after admission, however, she had a sudden cardiopulmonary arrest due to a cardiac tamponade. An emergency coronary angiography showed extravasation of the contrast into the epicardium from the branch of the circumflex artery. She was diagnosed with SCAR and underwent a successful coil embolization. However, she went into an irreversible coma due to the cerebral hypoxia. On Day 33, she died of pneumonia. An autopsy showed a rupture of the internal elastic layer of the coronary artery. However, no specific findings, such as aneurysm and dissection, were evident. The common atherosclerotic changes were observed. Discussion The stable condition lasting for over 2 weeks was a rare clinical course for SCAR. Long-term hypertension and dialysis would have caused the rupture of the coronary artery with common atherosclerotic changes. We should consider SCAR as one of the differential diagnoses when we observe pericardial fluid.

INTRODUCTION Pulmonary vein isolation (PVI) lesions after cryoballoon ablation (CBA) are wide and continuous, however, the distribution can depend on the pulmonary vein (PV) size. We sought to assess the relationship between the lesion distribution and PV size after CBA and hotballoon ablation (HBA). METHODS AND RESULTS A total of 80 consecutive patients who underwent PVI were enrolled (40 with CBA). The lesions were visualized by late-gadolinium enhancement magnetic resonance imaging. The lesion width, lesion gaps, and distance from the PV ostium (PVos) to distal lesion edge (DLE) were assessed. If the DLE extended inside the PV, the value was expressed as a negative value. Although the lesion width was significantly wider in the CB group (7.8 ± 2.0 vs 4.9 ± 1.0 mm, P

This study aimed to confirm the precise course of a pericardiocentesis with the anterior approach using post-procedural computed tomography (CT).Percutaneous epicardial ventricular tachycardia (VT) ablation has been increasingly performed. Although the inferior approach has been the common method, the feasibility of the anterior approach has subsequently been reported. However, the precise course of the anterior approach has not been presented.An epicardial ablation with the anterior approach was performed in 15 patients. At the end of the procedure, the epicardial sheath was exchanged for a drainage tube to monitor bleeding. Of those patients, in 9 procedures in 8 patients a CT scan was performed just after the procedure to confirm the course of the drainage tube and to rule out any complications. Epicardial ablation was indicated for a failed endocardial VT ablation in 7 patients and epicardial substrate modification in 1 patient with Brugada syndrome.Volume-rendered images reconstructed from CT demonstrated each course of the drainage tubes and their relation to the surrounding organs. These images revealed that the tube had a curved trace, and did not penetrate the diaphragm or pass through the abdominal cavity. No injury to the surrounding organs was detected in any of the cases.The precise course of the drainage tube placed along the trajectory of the anterior approach was able to be confirmed using post-procedural CT images. These images support the safety and feasibility of the anterior approach from the anatomic standpoint with a low incidence of abdominal viscera injury.

Cardiac accessory pathways (APs) in Wolff–Parkinson–White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.

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 Air embolisms are serious complications during catheter ablation procedures. Objectives The aims of the present study were to determine when air bubbles enter the left atrium (LA) during catheter ablation procedures and to identify techniques that reduce air bubble intrusion. Methods An ex vivo study was performed to monitor air bubbles using a silicone heart model and a high-resolution camera. In total, 280 radiofrequency catheter and cryoballoon ablation processes were tested. Results Small and large air bubbles were often observed during catheter ablation processes. Many small air bubbles arose during sheath flushing at fast speeds (15 mL/2 s) (median bubble number [quartiles]: 35 [20–53] for SL0, 35 [23–44] for Agilis, and 98 [91–100] for FlexCath) and during initial cryoballoon inflation/freezing/deflation (34 [22–47]). Large (≥1.5 mm) air bubbles were observed during Lasso catheter insertion (1 [0–1]), cryoballoon insertion (2 [1–2]), and initial inflation/freezing/deflation (1 [1–3]). Massive air bubbles were observed during Optima catheter insertion into the sheath using an inserter (10 [2–15]). Sheath flushing at slow speeds (15 mL/5 s) significantly reduced the number of air bubbles. Before cryoballoon insertion, temporary balloon inflation and air bubble removal from the inflated surface were most effective in reducing air bubble intrusions. Optima catheter insertion without an inserter significantly reduced large air bubble intrusion. Conclusion Air bubbles entered the LA at specific times. Techniques such as sheath flushing at slow speeds, temporary cryoballoon inflation before insertion, inserting the Optima catheter without an inserter, and avoidance of negative pressure in the LA could reduce air bubble intrusion.

Background— This study sought to investigate external photon beam radiation for catheter-free ablation of the atrioventricular junction in intact pigs. Methods and Results— Ten pigs were randomized to either sham irradiation or irradiation of the atrioventricular junction (55, 50, 40, and 25 Gy). Animals underwent baseline electrophysiological evaluation, cardiac gated multi-row computed tomographic imaging for beam delivery planning, and intensity-modulated radiation therapy. Doses to the coronary arteries were optimized. Invasive follow-up was conducted ≤4 months after the irradiation. A mean volume of 2.5±0.5 mL was irradiated with target dose. The mean follow-up length after irradiation was 124.8±30.8 days. Out of 7 irradiated animals, complete atrioventricular block was achieved in 6 animals of all 4 dose groups (86%). Using the same targeting margins, ablation lesion size notably increased with the delivered dose because of volumetric effects of isodose lines around the target volume. The mean macroscopically calculated atrial lesion volume for all 4 dose groups was 3.8±1.1 mL, lesions extended anteriorly into the interventricular septum. No short-term side effects were observed. No damage was observed in the tissues of the esophagus, phrenic nerves, or trachea. However, histology revealed in-field beam effects outside of the target volume. Conclusions— Single-fraction doses as low as 25 Gy caused a lesion with interruption of cardiac impulse propagation using this respective target volume. With doses of ≤55 Gy, maximal point-doses to coronary arteries could be kept

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

The brain dynamics of social behavior are important for understanding the group intelligence that occurs in humans. Coordinated behavior between two subjects has been used as an experimental model of social behavior, but the creativity occurring in a group of multiple persons has not yet been discussed. In this study, a rhythmic communication task was proposed as a model of social communication, and simultaneous electroencephalogram (EEG) of three subjects were evaluated. Results showed that the decrease of theta-band power in the EEG was correlated with the rhythm delay in the ensemble pattern, and the decreases of upper and lower alpha-band power were associated with the rhythm tempo and the rareness of ensemble pattern. This suggests that the theta- and alpha-band powers in the EEG associate with social communication and cross-frequency EEG dynamics is essential for understanding the creativity in the social behavior.

High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40–55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Background— Formation of microemboli during catheter ablation has been suggested as a cause for asymptomatic cerebral emboli. However, it is unknown which part of the process and ablation setting/strategy is most strongly related to this occurrence. Methods and Results— A total of 27 pigs were used. Catheter/sheath manipulations in left atrium were performed in 25 of 27 pigs outfitted with microemboli monitoring systems. Ablations using open-irrigated radiofrequency catheters were performed in 18 of 25 pigs. Two of 27 pigs did not undergo left atrial procedures and were injected with microembolic materials in the carotid artery to serve as positive controls. In total, 334 sheath/catheter manipulations (transseptal puncture, sheath flushing, catheter insertion, pulmonary vein venography, and sheath exchange) and 333 radiofrequency applications (power setting, 30/50 W; point-by-point/drag ablations) were analyzed. High microbubble volume in the extracorporeal circulation loop and a high number of microembolic signals in carotid artery were observed during sheath/catheter manipulations especially in saline/contrast injections at fast speed and ablations with steam pop. Fast sheath flushing produced significantly higher microbubble volume than slow sheath flushing (median, 12 200 versus 121 nL; P Conclusions— Formation of microbubbles was the greatest during fast saline/contrast injections and steam pops, whereas high-power radiofrequency applications, drag ablations, and steam pops produced most of the microparticles.

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)

SummaryWe describe a case of a 60-year-old male with dilated phase of hypertrophic cardiomyopathy caused by Fabry disease. He was diagnosed to have a cardiac variant of Fabry disease by an enzyme assay and a right ventricular endomyocardial biopsy which revealed specific features of this disease and cardiac involvement was the sole manifestation. He has developed dilated cardiomyopathy with sustained atrial flutter and frequent non-sustained ventricular tachycardia requiring isthmus ablation and cardiac resynchronization therapy with defibrillator.

Introduction: Highly precise irradiation using carbon-12 (12C) ions is a new means for catheter-free ablation. Besides energy deposition leading to the dose distribution, nuclear interactions lead to by-product β+-activity that can be measured using positron-emission-tomography (PET). Hypothesis: In-beam PET scanning during focused myocardial irradiation using 12C can adequately depict 12C dose deposition. Methods: Pigs were irradiated with 25, 40, and 55 Gy for AV node (AVN), LA-PV junction, and local LV freewall ablations. PET measurement was performed by means of a double head camera system installed at irradiation site. Coincidences were captured in end-expiration during beam extraction pauses of the accelerator. Results: Evaluation of PET images was qualitatively performed using the coronal plane of the activity distribution superimposed on the contrast-CT in the center of the target contour. Strong β+-activities were measured in AVN and LV ablations. In AVN ablations, activity was localized to the target location, without target activity spreading to the level of the aortic root or coronary sinus (Figure A). Local LV irradiations revealed strong activity in the target location, slightly extending into left lung and chest wall (Figure B). In 55 Gy animals, the cardiac entry channel showed increased activity, decreasing in 40 Gy and more so in 25 Gy animals. Conclusion: This is the first study applying in-beam PET to track 12C dose-deposition into the target location for catheter-free ablation in intact animals. Correlation of β+-activity to electrophysiological outcome, lesion induction, and potential side-effects may be critically important in dosing therapy and predicting outcomes.

Background— The differences in ablation characteristics of freezing time and balloon size using second generation cryoballoon are still unknown. Methods and Results— Twenty-six dogs underwent pulmonary vein (PV) isolation. Balloon and tissue temperatures (left atrial–PV junction, phrenic nerve, and internal esophagus) were monitored. The ablation duration was randomized to either 3 or 4 minutes, which did not show significant differences in temperature profiles, PV isolation success rate, complications, or histological changes. Twenty dogs underwent cryoablation using 28-mm cryoballoon, 6 dogs were done using the 23-mm cryoballoon. Positioning of the 23-mm cryoballoon was more distal in the PV, which resulted in better PV occlusion. Temperature profiles showed lower temperatures in the 23-mm cryoballoon than in the 28-mm cryoballoon (inner balloon, median [range]: −51.5 [−66.0 to −31.0] versus −43.0 [−64.0 to −26.0]°C, P P P Conclusions— The efficacy of 3-minute ablation was not significantly different from 4-minute ablation in dogs. The 23-mm cryoballoon had a greater cooling effect than the 28-mm cryoballoon for small PVs, but showed narrower ablative lesions in the left atrial antrum.

Background— Thermodynamics in the left atrium–pulmonary vein (PV) junction, phrenic nerve, and esophagus during PV isolation (PVI) using the second-generation cryoballoon are not known. Methods and Results— Twenty dogs underwent PVI using second-generation cryoballoon. Ablations were performed for ≤2 deliveries based on PVI without a bonus freeze. Inner balloon, balloon surface, and tissue temperatures were monitored during cryoablation. The tissue thermocouples were placed on the epicardial surface of the left atrium–PV junction, as well as on the phrenic nerve and within the esophagus. A total of 259 cryoballoon and 229 tissue tissue thermocouples profiles during 53 cryoablations of 40 PVs were analyzed. Acutely, PVI was achieved in 36 of 40 PVs (90%). Conductive tissue cooling spread radially from the balloon–left atrium–PV contact point. The lowest tissue temperatures were dependent on the distance of the tissue thermocouples to the balloon surface ( r =0.85; P Conclusions— Variance in tissue thermodynamics during cryothermal ablation depends on the distance from balloon and peri-balloon blood flow leaks. This information may be useful for successful PVI without severe complications.

Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.

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

Background: The upper lim it of vulnerability (UL V) closely correlates with the defibrillation threshold (OFT) . The aim of th is study was to establish the optimal protocol for using the UL V test to predict high OFT (>20 J) without inducing ventricular fibrillation (VF) . Methods and Results: The 10-J and 15-J ULV test with 3 coupling intervals (-20, 0, and +20ms to the peak of T-wave) and the OFT test were performed in 96 patients receiving implantable cardioverter defibrillator. ULV ::; 10J was confirmed in 47 (49%). ULV ::; 15J was confirmed in 70 (77%) of 91 patients (15-J ULV test could not be done in 5). The sensitivity and negative predictive value of both ULV > 1 OJ and> 15J for predicting high OFT were 100%. The specificity and positive predictive value of ULV > 15 J were higher than those for ULV > 1 OJ (85% vs. 55%, 43% vs. 22%, respectively). The rate of VF inducibility for confirming ULV ::; 15J was lower than that for ULV ::; 10J (23% vs. 51 %, P

Slow pathway (SP) ablation of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) can be complicated by unexpected AV block even at sites10 mm inferior to the bundle of His (HB), and one cause is thought to be the inferior dislocation of an antegrade fast pathway (A-FP). We assessed locations of FPs guided by CARTO.Sites of FPs were mapped guided by CARTO before SP ablation in 18 patients with slow-fast AVNRT. The A-FP was defined as the site with the minimum interval between the stimulus and HB potential when pace mapping in the right atrial septum.The A-FP was 7.9 ± 7.5 mm inferior and 2.9 ± 5.0 mm posterior to the HB. In 6 of 18 patients (33%), the A-FP was inferiorly dislocated10 mm to the HB. SP ablation was successfully performed in all patients at sites10 mm from both the HB and the A-FP without AV block. In the inferiorly dislocated A-FP group, A-FPs seemed to be positioned much more on atrial sites and sufficiently posterior to SP ablation sites.The A-FP inferiorly dislocated10 mm to the HB in one third of patients with AVNRT and seemed to be positioned deep on atrial sites. It is again emphasized that SP ablation within the triangle of Koch should be performed at a very ventricular annulus site, particularly in the inferiorly dislocated A-FP group.

Background: The posteromedial right atrium (PMRA) forms a block line during typical atrial flutter (AFL). However, whether upper turnover portion exists at the anterior or posterior superior vena cava (SVC) has not been determined. Methods: We performed right atrial mapping during AFL in 20 patients (typical AFL, n = 17; reverse typical AFL, n = 3) using an electroanatomical mapping system. Results: Mean AFL cycle length was 224 ± 20 ms and mean number of mapping points was 140 ± 27. PMRA formed a block line during both typical and reverse AFL in all patients. However, in 16 of 17 patients mapped with typical AFL, PMRA did not extend superiorly to the orifice of the SVC and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. In the remaining patient mapped with typical AFL, a double potential was recorded along the PMRA continuously between the orifices of the inferior vena cava (IVC) and SVC. In the three patients mapped with reverse typical AFL, a posterior barrier was detected from IVC to the upper limit of the PMRA and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. Mean length from IVC to upper limit of the PMRA was 81 ± 8% of the length from IVC to SVC. Conclusions: PMRA forms a functional block line during both typical and reverse typical AFL. The upper turnover portion of reentry circuit for AFL was observed between the upper limit of the PMRA and the posterior SVC in the majority of isthmus-dependent AFL patients.

We investigated the differences in the endocardial substrates between ischemic cardiomyopathy (ICM) and non-ICM (NICM) by using electro-anatomical mapping and pace-mapping. We studied 18 patients (ICM and NICM, 9 each) with monomorphic ventricular tachycardia (VT) documented by 12-leads ECG. Low voltage area was defined by signal amplitude1.5 mV. A pace-map QRS morphology that matched VT in10 of the 12-leads ECG was regarded as a pace-map match. And conduction delay during pace-mapping was defined as the stimulus to QRS intervalor=40 ms. Low voltage area was 53.8 +/- 21.5 and 20.8 +/- 16.7 cm2 in ICM and NICM patients, respectively (P = 0.002). Pace-mapping was assessed in 6 ICM and 9 NICM. Pace-map match with conduction delay were obtained in all the 6 ICM patients. But in NICM patients, pace-map match with conduction delay was obtained in 3 patients. Pace-map match sites where conduction delay was not observed were obtained in 5 patients. Pace-map match could not be obtained in 1 patient. We attempted ablation in 6 ICM and 7 NICM patients. Subsequently, VT recurrence was not observed in ICM but it was observed in 6 of 7 NICM patients (log-rank P = 0.0016). In NICM patients, the arrhythmogenic substrate that represented the abnormal electrogram and conduction delay was observed less within the endocardial surface when compared with that observed in ICM. VT recurrence rate subsequent to endocardial ablation was higher in NICM than in ICM patients.

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.