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Abstract Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte–macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B+ macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B+ macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF.

Abstract Background Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all‐cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results Not applicable. Conclusion This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Abstract Background Atrioventricular nodal reentrant tachycardia (AVNRT) sometimes recurs even after anatomical slow pathway (SP) ablation targeting the rightward inferior extension (RIE). This multicenter study aimed to determine the reasons for AVNRT recurrence. Methods and Results Forty‐six patients were treated successfully for recurrent AVNRT. Initial treatment was for 38 slow‐fast AVNRTs, 3 fast‐slow AVNRTs, 2 slow‐slow AVNRTs, 2 slow‐fast and fast‐slow AVNRTs, and 1 noninducible AVNRT. All initial treatments were of RF application to the RIE; SP elimination was achieved in 11, dual AVN physiology was seen in 29, and AVNRT remained inducible in 5. The recurrent AVNRTs included 34 slow‐fast AVNRTs, 6 fast‐slow AVNRTs, 3 slow‐slow AVNRTs, 2 slow‐fast and fast‐slow AVNRTs, and 1 slow‐fast and slow‐slow AVNRTs. Successful ablation site was within the RIE in 39 and left inferior extension in 7. In 30 of 39, the successful RIE site was in the same area or higher than that of the initial procedure. Conclusion For a high majority (around 85%) of patients in whom AVNRT recurs after initial ablation success, the site of a second successful procedure will be within the RIE even though the RIE was originally targeted. Furthermore, a high majority (around 86%) of sites of successful ablation will be higher than those originally targeted.

Abstract 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 radiofrequency (RF) ablation and the factors attributing to the VT recurrence. Methods We analyzed that 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; p

Abstract Background It is uncertain whether cardiac resynchronization therapy with a defibrillator (CRT‐D) provides better survival benefits than a CRT‐pacemaker (CRT‐P) in heart failure patients with a reduced ejection fraction (≦35%, HFrEF) treated with contemporary HF therapy. Methods We retrospectively analyzed the ventricular arrhythmia (VAs; sustained ventricular tachycardia/fibrillation) events in HFrEF patients who underwent CRT without a prior history of VAs or aborted sudden cardiac death before the CRT implantation. Between January/2010 and December/2020, a CRT device was implanted in 79 HFrEF patients (mean age: 69 ± 12 years, male: 57, ischemic cardiomyopathy: 16). CRT‐D and CRT‐P devices were implanted in 50 and 29 patients, respectively, at each physician's discretion. CRT‐Ds were indicated in younger patients than were CRT‐Ps (66 ± 12 vs. 73 ± 12 years, p = 0.03), but the gender distribution did not differ (female, 24% [12 of 50] vs. 35% [10 of 29], p = 0.44). The VA events during a median follow‐up of 3.5‐years (interquartile range [IQR]:1.6–5.5) and their predictors were analyzed. Results VA events occurred in 9 patients with CRT‐Ds (18%) and one with a CRT‐P (3%, p = 0.08). The VA event rate was significantly lower in patients without a prior non‐sustained ventricular tachycardia (NSVT: ≥3 beats; rate, ≥120 bpm; lasting

Abstract Background Corticosteroids are widely used in patients with cardiac sarcoidosis (CS). In addition, upgrading to cardiac resynchronization therapy (CRT) is sometimes needed. This study aimed to investigate the impact of corticosteroid use on the clinical outcomes following CRT upgrades. Methods A total of 48 consecutive patients with non‐ischemic cardiomyopathies who underwent CRT upgrades were retrospectively reviewed and divided into three groups: group 1 included CS patients taking corticosteroids before the CRT upgrade (n = 7), group 2, CS patients not taking corticosteroids before the CRT upgrade (n = 10), and group 3, non‐CS patients (n = 31). The echocardiographic response, heart failure hospitalizations, and cardiovascular deaths were evaluated. Results The baseline characteristics during CRT upgrades exhibited no significant differences in the echocardiographic data between the three groups. After the CRT upgrade, responses regarding the ejection fraction (EF) and end‐systolic volume (ESV) were significantly lower in CS patients than non‐CS patients (ΔEF: group 1, 6.7% vs. group 2, 7.7% vs. group 3, 13.6%; p = .039, ΔESV: 3.0 ml vs. ‐12.7 ml vs. ‐37.2 ml; p = .008). The rate of an echocardiographic response was lowest in group 1 (29%). There were, however, no significant differences in the cumulative freedom from a composite outcome among the three groups (p = .19). No cardiovascular deaths occurred in group 1. Conclusion The echocardiographic response to an upgrade to CRT and the long‐term prognosis in patients with CS should be carefully evaluated because of the complex etiologies and impact of immunosuppressive therapy.

Abstract Background Some of atrial fibrillation (AF) drivers are found in normal/mild late‐gadolinium enhancement (LGE) areas, as well as moderate 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 normal/mild 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), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to

Abstract Knowing the vascular anatomy of the common femoral artery bifurcation and ultrasound‐guided puncture, including doppler, is helpful in recognizing anatomic variations and avoiding complications.

Introduction Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients’ postablation quality of life (QoL) and long-term clinical outcomes.Methods and analysis We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician’s advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient’s Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results.Ethics and dissemination The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals.Trial registration number UMIN000047023.

Abstract 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.

Abstract 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.

Abstract Background Although anticoagulation therapy could reduce the risk of strokes in patients with atrial fibrillation (AF), large‐scale investigations in the direct oral anticoagulant (DOAC) and AF catheter ablation (CA) era are lacking. Methods This study was designed as a prospective, multicenter, observational study and a total of 2113 patients from 22 institutions were enrolled in the Hyogo area. Results The mean age and CHADS2 score were 70.1 ± 10.8 years old and 1.5 ± 1.1, respectively. The follow‐up period was 355 ± 43 days. CA was performed in 614 (29%) and DOACs were prescribed in 1118 (53%) patients. Ischemic strokes/systemic embolisms (SEs) and major bleeding occurred in 13 (0.6%) and 17 (0.8%) patients, respectively. New onset dementia, hospitalizations for cardiac events, and all‐cause death occurred in eight (0.4%), 60 (2.8%), and 29 (1.4%) patients, respectively. A multivariate analysis demonstrated that persistent AF and the body weight (BW) were associated with ischemic strokes/SEs and major bleeding, respectively (persistent AF: hazard ratio, 9.57; 95%CI, 1.2‐74.0; P = .03; BW: hazard ratio, 0.94; 95%CI, 0.90‐0.99; P = .02). AFCA history was associated with the cardiac events (hazard ratio, 0.44; 95%CI, 0.20‐0.99; P = .04). Age was associated with new onset dementia (hazard ratio, 1.1; 95%CI, 1.0‐1.2; P = .03). Conclusions In the DOAC and CA era, the incidence of ischemic strokes/SEs, major bleeding and cardiac events could be dramatically reduced in patients with AF. However, some unsolved issues of AF management still remain especially in elderly patients with persistent AF and a low BW.

Abstract 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.

Abstract 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.

Abstract 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.

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.

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 <7Gy, but target conformity of lesions was not fully achieved using this approach. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]