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Aims To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). Methods and results We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. Conclusion Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

A 61-year-old woman with a low thromboembolic risk was scheduled to undergo pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation. Transthoracic echocardiography showed no cardiac structural abnormality. Intracardiac echocardiography (ICE) identified a small left atrium mass attached to the atrial septum and the procedure was stopped before the transseptal puncture; the surgically resected tumor was cardiac myxoma. ICE is a reliable imaging modality to exclude left atrial thrombus. However, unusual and unexpected cardiac structures also prevent performing PVI, which pre-procedural transesophageal echocardiography could identify. Imaging options should be further discussed to improve patient care and safety.

Parallel connection of an electrophysiology recording system (EP system) to equipment for conduction system pacing (CSP) has been widely used for fine monitoring of intracardiac electrograms and pacing evaluation. We experienced a case showing unexpected pacing threshold exacerbation under specific conditions when the EP system was connected in parallel. We evaluated the underlying mechanism using an ex vivo model. An ex vivo pacing and intracardiac electrogram monitoring model was generated using an oscilloscope, pacing system analyzer (PSA), EP system, and simulated heart. The discrepancy between expected output at the PSA and the actual measured output value at the simulated heart was measured under various conditions and using various combinations of pacing equipment. Parallel connection of the EP system was associated with reduced electrical output from the PSA as recorded at the simulated heart. The unexpected adverse effects were particularly noticeable when using an RMC-5000 EP system with the pacing function on. The trouble is completely resolved by simply turning off the pacing function of the system. There is a possibility that the EP system might increase the pacing threshold in CSP when the PSA and EP system is are deployed in parallel. The issue may provoke pseudo failure of CSP due to the high pacing threshold. When the RMC-5000 is used for conduction system pacing in parallel with a PSA for the pacing test, the pacing function of RMC-5000 should be turned off.

Repeated hospitalization for heart failure (HF) is a strong predictor of mortality among HF patients. While recent cardiac electrical implantable devices (CIEDs) can detect worsening HF through remote monitoring1,2, there is no early detection system for HF progression in patients at home without a CIED. We therefore developed an artificial intelligence-based HF detection system that uses single-lead electrocardiograms (ECGs) recorded at home. Our convolutional neural network (CNN) model calculated a novel HF-index from the estimated NYHA grades as a quantitative indicator of HF severity. Retrospective data revealed a strong correlation between HF-indexes and plasma BNP levels (R=0.91).A prospective clinical study confirmed the accuracy of the HF severity judged from the estimated HF-index using a portable single-lead ECG monitor at home.We have thus successfully constructed a novel, at-home HF monitoring system for a portable single-lead ECG device, which enables early detection and early medical intervention in HF.

A 41-year-old man developed cardiac arrest. A resting 12-lead electrocardiogram showed a delta wave, suggestive of preexcitation syndrome. An electrophysiological test revealed the existence of inducible atrial fibrillation and a fasciculoventricular accessory pathway (FVAP). After these examinations, idiopathic ventricular arrhythmia was suspected. For evaluating concealed Brugada syndrome, pilsicainide was administered, which diminished the delta wave and no Brugada-like electrocardiogram was observed. Ventricular double extra-stimulation from the RV apex easily induced VF, which could not be defibrillated by an external defibrillator, and later stopped spontaneously. These results established the diagnosis of FVAP and idiopathic VF, and not pre-excited atrial fibrillation or Brugada syndrome.

Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death., Cardiac immune cells play various roles in the maintenance of homeostasis and diseases in the heart. Here the authors show that cardiac resident macrophages are a critical regulator of cardiac impulse conduction through amphiregulin production, contributing to the prevention of sudden death.

Background: In patients undergoing catheter ablation (CA) for atrial fibrillation (AF), the use of uninterrupted direct oral anticoagulants (DOACs) is the current protocol. This study evaluated bleeding complications following the uninterrupted use of 4 DOACs in patients undergoing CA for AF without any change in the dosing regimen. Moreover, we assessed differences between once- and twice-daily DOAC dosing in patients undergoing CA for AF who continued on DOACs without any change in the dosing regimen. Methods and Results: This study was a retrospective single-center cohort study of consecutive patients. All patients continued DOACs without interruption or changes to the dosing schedule, even in the case of morning procedures. The primary endpoint was the incidence of major bleeding events within the first 30 days after CA. In all, 710 consecutive patients were included in the study. Bleeding complications were less frequent in the uninterrupted twice- than once-daily DOACs group. However, the incidence of cardiac tamponade across all DOACs was low (0.98%; 7/710), suggesting that uninterrupted DOACs without changes to the dosing regimen may be an acceptable strategy. The rate of total bleeding events, including minor bleeding (12/710; 1.6%), was also satisfactory. Conclusions: Uninterrupted DOACs without any change in dosing regimen for patients undergoing CA for AF is acceptable. Bleeding complications may be less frequent in patients receiving DOACs twice rather than once daily.

Background In patients undergoing AF catheter ablation (CA), uninterpreted DOACs reduced bleeding events without increasing ischemic events compared with vitamin K antagonist, and the continuation of anticoagulants is recommended for AF ablation. However, in the past studies, patients received once-daily DOACs in the evening, not in the morning of the procedure day. Moreover, there has been no study comparing uninterrupted 4 DOACs; therefore, the safety and effect of uninterpreted DOACs taken just in the morning of AF ablation is unknown. Objective The purpose of this study was to compare bleeding complications and thromboembolism events between 4 DOACs in patients undergoing AF ablation. Method This study was the retrospective single-center cohort study of consecutive patients who underwent AF ablation between April 2014 to July 2019. All patients continued DOAC uninterruptedly including just in the morning of the procedure. The primary endpoint included major bleeding events within the first 30 days after CA. The secondary endpoints included the composite events of ischemic stroke, systemic embolism, myocardial infarction, and vascular death. Result A total of 713 patients (mean age 64±12 years, 72% male) were included in this analysis; enrolled patients were 88, 238, 218, and 169 respectively in dabigatran, rivaroxaban, apixaban and edoxaban group. At the baseline, the ratio of age ≥75 years and CHADS2 score was higher in apixaban group, though all other baseline variables were similar between them. The primary endpoint was observed 0%, 2.1%, 0.45%, and 4.7% respectively in dabigatran, rivaroxaban, apixaban, and edoxaban group (P=0.013) without significant difference about secondary endpoint between them (P=0.3). Comparing twice-daily vs once-daily DOACs, the primary endpoint was observed significantly lower in the twice-daily group than in once-daily group (0.32% and 3.2% respectively, P=0.0054), without any significant difference about secondary endpoint (0% and 0.73% respectively, P=0.26). Conclusion Taking DOACs also in the morning of AF ablation, uninterrupted twice-daily DOACs are safer than once-daily DOACs without increasing ischemic event, although twice-daily DOACs, especially apixaban, were used in higher aged patients. Figure 1 Funding Acknowledgement Type of funding source: None

Convolutional neural networks (CNNs) applied to electrocardiograms (ECGs) have been showing utility for detecting left ventricular (LV) dysfunction1. Although early detection of reduced LV ejection fraction (rEF) could improve handling of heart failure (HF) with rEF (HFrEF), it is not sufficient to detect HF with preserved EF (HFpEF). Here we developed a CNN algorithm to classify the severity of HF based on single-lead ECG data, irrespective of EF. We trained a CNN using ECG data and the HF classification from 7,865 patients with HF. The CNN achieved an area under the receiver-operating characteristic curve (AUC) of 0.996 for distinguishing patients with HF of various severity from healthy controls. It is anticipated that early detection of HF and therapeutic management of HF patients can be improved by employing this CNN with a single-lead ECG device.

Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA),lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages.lncFAOis induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chimonocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found thatlncFAOdirectly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO.lncFAOdeletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism,lncFAOacts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.

Although beta-blockade itself is not a first choice for chronic kidney disease (CKD) patients, alpha-beta-blockers (ABB) do improve their prognoses. This study's aim was to evaluate the effect of beta-selective-blockers (BSB) and ABB on circadian cardiac autonomic activity in CKD patients.The study consisted of 496 non-diabetic individuals who underwent 24-hour Holter monitoring (149 CKD patients and 347 controls without CKD). Using heart rate variability analysis, we evaluated the proportion of NN50 and the high-frequency component (reflecting parasympathetic activity), and low- to high-frequency ratio (reflecting sympathovagal balance). These indices were evaluated by regression analysis incorporating gender, age, related comorbidities, and medications. BSB increased vagal activity only in the day-time and not the night-time in controls. In CKD patients, BSB was significantly related to higher vagal activity throughout the day and with lower sympathovagal balance at night. The night sympathovagal balance of CKD patients taking ABB was significantly higher than that of CKD patients taking BSB, which was the only significant difference between the effects of BSB and ABB.The sympatholytic therapy effect is different depending on CKD presence and whether patients are treated with BSB or ABB. In CKD patients without severe heart failure, BSB could be associated with higher parasympathetic activity and lower sympathovagal balance compared to ABB.

Background Periprocedural anticoagulation is important in catheter ablation (CA) of atrial fibrillation (AF) and there is increasing evidence that uninterrupted vitamin K antagonist (VKA) therapy is superior to interrupted anticoagulation strategies. Since the emergence of direct oral anticoagulants (DOACs), numerous studies have shown promising results for their use in uninterrupted strategies. However, further studies are needed to further define the efficacy and safety of performing AF ablation with uninterrupted factor XA inhibitors or direct thrombin inhibitors.Methods and Results:We have performed CA of AF without discontinuation of either VKA or DOAC therapy since April 2014. A total of 376 patients with AF underwent CA including pulmonary vein isolation. All of the patients were divided into 2 groups (uninterrupted VKA or uninterrupted DOACs). Anticoagulation with DOACs was associated with fewer complications than uninterrupted VKA therapy (P=0.04). There were significant differences between groups in the rates of congestive heart failure, left ventricular ejection fraction, body weight, and estimated glomerular filtration rate and of the CHADS2, CHA2DS2-VASc and HAS-BLED scores. Therefore, we also analyzed the results using the propensity score-matching method. We found no significant difference in periprocedural complications between uninterrupted VKA or DOACs therapy (P=0.65). Conclusions CA of AF without discontinuation of DOACs is not inferior to CA without discontinuation of a VKA, with regard to ischemic or hemorrhagic complications.

Coronary stent fracture (SF) is rare as a complication of percutaneous coronary intervention (PCI), and its adverse events are increasingly being recognized with the development in devices of PCI. The major adverse events caused by SFs are in-stent restenosis due to neointimal overgrowth caused by poor drug delivery.1,2) A coronary artery aneurysm (CAA) is a rare complication of SF, but may lead to lethal events such as acute coronary syndrome or rupture of the CAA further leading to cardiac tamponade.3-5) However, the management of CAAs is controversial with or without SF.6) Herein, we report a case of a CAA caused by an SF and discuss the management of CAA complicated with SF, along with a literature review. We suggest that surgical treatment should be considered the higher-priority strategy in the cases of CAA with SF as compared to CAA without SF.

A 41-year-old man developed cardiac arrest. A resting 12-lead electrocardiogram showed a delta wave, suggestive of preexcitation syndrome. An electrophysiological test revealed the existence of inducible atrial fibrillation and a fasciculoventricular accessory pathway (FVAP). After these examinations, idiopathic ventricular arrhythmia was suspected. For evaluating concealed Brugada syndrome, pilsicainide was administered, which diminished the delta wave and no Brugada-like electrocardiogram was observed. Ventricular double extra-stimulation from the RV apex easily induced VF, which could not be defibrillated by an external defibrillator, and later stopped spontaneously. These results established the diagnosis of FVAP and idiopathic VF, and not pre-excited atrial fibrillation or Brugada syndrome.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions.

Malignant melanoma is one of the untreatable cancers in which conventional therapeutic strategies, including chemotherapy, are hardly effective. Therefore, identification of novel therapeutic targets involved in melanoma progression is urgently needed for developing effective therapeutic methods. Overexpression of interleukin-13 receptor α2 (IL13Rα2) is observed in several cancer types including glioma and pancreatic cancer. Although IL13Rα2 is implicated in the progression of various types of cancer, its expression and roles in the malignant melanoma have not yet been elucidated. In the present study, we showed that IL13Rα2 was expressed in approximately 7.5% melanoma patients. While IL13Rα2 expression in human melanoma cells decreased their proliferation in vitro, it promoted in vivo tumour growth and angiogenesis in melanoma xenograft mouse model. We also found that the expression of amphiregulin, a member of the epidermal growth factor (EGF) family, was correlated with IL13Rα2 expression in cultured melanoma cells, xenograft tumour tissues and melanoma clinical samples. Furthermore, expression of amphiregulin promoted tumour growth, implicating causal relationship between the expression of IL13Rα2 and amphiregulin. These results suggest that IL13Rα2 enhances tumorigenicity by inducing angiogenesis in malignant melanoma, and serves as a potential therapeutic target of malignant melanoma.

The Bentall procedure is a surgical technique for an ascending aortic or aortic aneurysm in combination with valve disease. A well-known uncommon complication of after the Bentall procedure is coronary artery stenosis related to coronary anastomosis of an interposed graft. We report on a 73-year-old woman who presented with heart failure secondary to graft stenosis of the right coronary artery 6 months after undergoing a modified Bentall procedure. Percutaneous coronary intervention (PCI) was performed and type II coronary artery perforation occurred during PCI of the right coronary artery. We used a perfusion balloon and achieved hemostasis successfully. We report a case of coronary artery perforation that was treated with perfusion balloon during PCI in a patient with a prior modified Bentall procedure. In addition, we present a case series of PCI for ostial coronary stenosis after the Bentall procedure.

Coronary stent fracture (SF) is rare as a complication of percutaneous coronary intervention (PCI), and its adverse events are increasingly being recognized with the development in devices of PCI. The major adverse events caused by SFs are in-stent restenosis due to neointimal overgrowth caused by poor drug delivery.

Malan syndrome has recently been characterized to present Sotos-like phenotypes, such as intellectual disability and macrocephaly, with mutations in the NFIX gene. Herein, we report a 38-year-old patient with a novel single adenine insertion mutation in exon 2 of the NFIX gene (c.290_291insA). He developed early-onset thoracic aortic aneurysm and dissection, which was a rare complication but deserves particular attention in relatively long-lived patients with Sotos-like phenotypes.

Thrombotic microangiopathy (TMA) is a rare but lethal multisystem disease characterized by peripheral thrombocytopenia, microangiopathic hemolytic anemia, fever, and various stages of renal and neurological dysfunctions.(1,2)) The causes of TMA are mainly thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS), and cases of TMA related to myelodysplastic syndrome (MDS) are quite rare. Herein, we report a case of acute myocardial infarction (AMI) caused by TMA which is strongly suspected to have a relationship to MDS, and discuss the treatment of our patient who needed antiplatelet or anticoagulant therapy after AMI, while on the other hand, had pancytopenia and a bleeding event due to MDS.

Concurrent chemoradiotherapy for regionally advanced stage III non-small cell lung cancer is the standard treatment method. However, the clinical implications of consolidation chemotherapy following chemoradiation have been unclear. Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy. The primary endpoint was the 1-year survival rate.Chemonaive PS 0-1 patients with stage IIIA/B NSCLC were enrolled. During the concurrent chemoradiation phase, patients were treated with weekly paclitaxel 40 mg/m(2) plus carboplatin AUC 2. The primary tumor and involved nodes received 60 Gy in 2-Gy fractions over 6 weeks. During the consolidation phase, vinorelbine 25 mg/m(2) on days 1 and 8 was repeated for three cycles.A total of 40 eligible patients (72.5 % male; median age, 63 years; range 29-74 years) were analyzed for efficacy. Squamous cell carcinoma was the most common histology (47.5 %), and more patients had clinical stage IIIB (55 %) cancer. The average radiation dose was 56.5 Gy, and the average number of carboplatin plus paclitaxel cycles was 4.93. Seventeen patients proceeded to the consolidation chemotherapy phase, and 14 completed three cycles of vinorelbine monotherapy. The objective response rate was 75.0 %, including 1 patient who achieved a complete response. Progression-free survival and overall survival (OS) were 46 weeks [95 % confidence interval (CI) 31-64 weeks] and 110 weeks (95 % CI 90-184 weeks), respectively. The OS rate at 1 and 2 years was 85.0 % (95 % CI 69.6-93.0 %) and 53.9 % (95 % CI 37.1-68.0 %), respectively.Concurrent chemoradiation with weekly carboplatin and paclitaxel followed by vinorelbine consolidation is effective for stage III non-small cell lung cancer and shows a generally mild toxicity profile.

Malan syndrome has recently been characterized to present Sotos-like phenotypes, such as intellectual disability and macrocephaly, with mutations in the NFIX gene. Herein, we report a 38-year-old patient with a novel single adenine insertion mutation in exon 2 of the NFIX gene (c.290_291insA). He developed early-onset thoracic aortic aneurysm and dissection, which was a rare complication but deserves particular attention in relatively long-lived patients with Sotos-like phenotypes.

45歳,男性.人間ドックの腹部エコー検査にて後腹膜の腫瘤を指摘され,当院を受診した.血液生化学検査では血中ノルアドレナリンとドーパミンの上昇を認めた. CTでは大動脈の左側,膵臓下縁に接する様に径約4cm大の腫瘤が認められ,膵由来の腫瘍が疑われたが,造影MRIで膵との境界が確認され否定的となった.血管造影では第12肋間動脈・第1腰動脈で腫瘍濃染像を認めた.以上の諸検査所見から神経原性腫瘍を最も強く疑い,手術を施行した.術中に著明な血圧の上昇を認め,一時手術を中断したが,降圧剤で対応し,腫瘍を摘出しえた.摘出標本は径3.8cm大の球形で線維性被膜を有し,割面は嚢胞状で一部充実性であった.病理組織学的所見では,腫瘍細胞が胞巣状に増殖しており,クロモグラニンAが陽性で, S-100陽性の特徴的な支持細胞が確認されることよりパラガングリオーマと診断した.良悪性の診断では, Ki-67陽性細胞が10%以下であることより良性と診断した.後腹膜パラガングリオーマは比較的稀な疾患であり文献的考察を加えて報告する.