Background There is growing evidence indicating a close relationship between inflammation and atrial fibrillation (AF). Although underlying inflammatory atrial cardiomyopathy may contribute to the development of AF, the arrhythmogenic remodeling caused by atrial inflammation has not been elucidated in detail. Herein, we examined electrical, structural, and autonomic changes in the atria in a mouse model of autoimmune myocarditis. Methods BALB/c mice were immunized with cardiac myosin peptide (MyHC-α 614–629 ) conjugated with complete Freund’s adjuvant on days 0 and 7. Susceptibility to AF was assessed using right-atrial burst pacing. Results The mice immunized with MyHC-α 614–629 showed an inflammatory atrial cardiomyopathy phenotype, with enlarged atria; a high degree of inflammatory cell infiltration primarily consisting of CD4 + T cells, CD8 + T cells, Ly6G low CD11b + macrophages, and CD11c + dendritic cells; and severe interstitial fibrosis with collagen deposition. These mice demonstrated significantly enhanced susceptibility to AF, as indicated by their increased AF induction rate and duration. In addition, the expression of potassium channels ( Kcnh2, Kcnd3 , and Kcnj2 ) and calcium handling-associated genes ( Cacna1c , Camk2 , Ryr2 , and Atp2a2 ) was downregulated. Connexin 40 expression was significantly downregulated, leading to frequent lateralization to the inflamed atrium. Sympathetic and parasympathetic innervation and neurotrophin expression (nerve growth factor and brain-derived neurotrophic factor) were upregulated in the inflamed atria. Conclusion Inflammatory atrial cardiomyopathy promotes susceptibility to AF via arrhythmogenic electrical, structural, and autonomic remodeling of the atria.

Cardiomyocytes are terminally differentiated cells and their regenerative capacity is limited. Cardiac mesoderm, a precursor for all cardiovascular lineages, is derived from lateral plate mesoderm. The cardiac mesoderm is a promising cell source for basic research and clinical applications due to its multipotency and proliferative capacity. Despite some success, direct reprogramming factors remain undefined.

Neutrophils are the main leukocytes involved in the early phase of myocardial infarction. As part of their anti-bacterial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin decorated with granule proteins including neutrophil elastase (NE). Increasing evidence suggests that this process also occurs in noninfectious, sterile inflammation such as myocardial infarction (MI). However, the pathological role of NETs in MI remains unknown. Here we show that the neutrophils form NETs in the myocardium after MI, which reveal significant NE proteolytic activity. When subjected to permanent coronary artery ligation, wild-type (WT) mice produced large quantities of NETs. In MI mice, gene expression of Annexin A1 (AnxA1), an anti-inflammatory and proresolving mediator, was upregulated, however, most AnxA1 protein was degraded accompanied with high elastase activity in the myocardium. Both NE deficiency and NE inhibitor sivelstat accelerated resolution of acute inflammation associated with increased amount of intact AnxA1 and improved survival and cardiac function after MI. DNase 1 treatment, which disrupts NETs, also accelerated resolution of inflammation in MI WT mice. In the DNase-treated mice, proteolytic activity of NE was attenuated and AnxA1 protein was less cleaved compared with vehicle-treated MI mice. This implies that NE attached to NETs has more intense proteolytic activity than free form of NE. Thus, NET-associated NE impairs resolution of acute inflammation after MI. Inhibiting NETosis or cleaving NETs may improve healing and reduce NET-driven excessive inflammation after MI.

OBJECTIVES This study sought to determine the feasibility of a novel simplified ablation protocol targeting only the pulmonary vein antrum using the radiofrequency hot-balloon catheter in patients with paroxysmal atrial fibrillation. BACKGROUND Radiofrequency hot-balloon (RHB) catheter has been recently introduced into clinical practice for pulmonary vein isolation (PVI). The authors hypothesized that a novel simplified ablation protocol targeting only the PV antrum with energy application for a longer time (single-shot technique) could be an alternative approach to achieve PVI, while avoiding unnecessary energy application at the PV ostium. METHODS A total of 61 consecutive paroxysmal atrial fibrillation patients (age 64.1 +/- 10.9 years, 48 male) who underwent antrum RHB-PVI were enrolled. Energy applications were performed following the pre-specified protocol only targeting the PV antrum. If the PVI was not achieved after 2 energy applications using the RHB, a touch-up ablation was performed. RESULTS Of 241 PV, including 3 left common PV, 194 (80%) were isolated exclusively using the RHB. The target PVI average per group of 15 consecutive procedures improved from 75% (initial 15) to 89% (last 16) of patients. The injected volume was greatest in the right superior PV (13.1 +/- 2.0 ml) and the smallest in the left inferior PV (10.8 +/- 1.1 ml), and 23 PV (9.5%) required over 15 ml (estimated balloon diameter of 30 mm). Periprocedural complications were noted in 3 patients (4.9%), but phrenic nerve injury was not observed. Sinus rhythm maintenance at 12-month follow-up was achieved in 57 patients (93%). CONCLUSIONS A novel simplified antrum RHB-PVI appears to be a feasible technique for the treatment of paroxysmal atrial fibrillation. (c) 2019 by the American College of Cardiology Foundation.

Atrial fibrillation (AF) is the most prevalent arrhythmia in the general population. There is a close association between chronic kidney disease (CKD) and AF. In recent years, attention has been focused on the relationship between AF and uremic toxins, including indoxyl sulfate (IS). Several animal studies have shown that IS promotes the development and progression of AF. IS has been shown to cause fibrosis and inflammation in the myocardium and exacerbate AF by causing oxidative stress and reducing antioxidative defense. Administration of AST-120, an absorbent of uremic toxins, decreases uremic toxin-induced AF in rodents. We have recently reported that patients with a higher serum IS level exhibit a higher rate of AF recurrence after catheter ablation, with serum IS being a significant predictor of AF recurrence. In this review, we discuss the possible mechanisms behind the AF-promoting effects of uremic toxins and summarize the reported clinical studies of uremic toxin-induced AF.

Renal dysfunction results in the accumulation of various uremic toxins, including indoxyl sulphate (IS), and is a major risk factor for atrial fibrillation (AF). Experimental studies have demonstrated that IS exacerbates atrial remodelling via oxidative stress, inflammation, and fibrosis. However, its clinical impact on AF-promoting cardiac remodelling has not been described. Therefore, the purpose of this study was to clarify the relationship between basal IS levels and the 1-year outcomes after catheter ablation for the treatment of AF. Our prospective observational study included data from 125 patients with AF who underwent catheter ablation. Over a 1-year follow-up period, AF recurrence was identified in 21 patients. The 1-year AF-free survival was significantly lower in patients with high serum IS levels (≥0.65 μg/mL) than in those with low IS levels (60.1 ± 10.4% versus 85.2 ± 3.9%, P = 0.007). Univariable analysis identified that an IS concentration ≥ 0.65 μg/mL was associated with AF recurrence (hazard ratio [HR] = 3.10 [1.26–7.32], P = 0.015), and this association was maintained in multivariate analysis (HR = 3.67 [1.13–11.7], P = 0.031). Thus, in patients undergoing AF ablation, serum IS levels at baseline independently predict the recurrence of arrhythmia.

Cerebral vasoconstriction during hypotension with ventricular tachycardia has been reported, but the underling mechanism was unclear. We tested a hypothesis that the cardiac contraction, i.e. heart rate and/or contractility, causes cerebral vasoconstriction and thereby a decrease in cerebral oxygenation during supraventricular tachycardia (SVT) and ventricular tachycardia (VT). Heart rate (HR), arterial blood pressure (AP), and the prefrontal tissue oxygen index (TOI) with near‐infrared spectroscopy were measured during electrophysiological study in 8 patients. We selected similar hypotension trials ranging from −30 to −50 mmHg in SVT (10 trials, 4 patients) and VT (9 trials, 4 patients), and then compared HR and TOI responses. Although the decreases in AP were similar in SVT and VT (−37 ± 2 vs. −38 ± 2 mmHg), the prefrontal TOI decreased greater in SVT than VT (−5.2 ± 0.4 vs. −3.3 ± 0.6%, P < 0.05). HR increased greater in SVT than VT (85 ± 3 vs. 74 ± 8 beats/min, P < 0.05), and the increase in HR correlated with the TOI fall (r = −0.80, P < 0.05). The ejection fraction in SVT and VT were 70 ± 2 and 44 ± 14%. These results suggest that a higher cardiac contraction with tachycardia may lead to decrease in cerebral oxygenation, which is irrespective of hypotension. Support or Funding Information This study is supported by Automotive and Medical Concert Consortium (AMECC) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Supraventricular tachycardia (SVT) causes hypotension and cerebral hypoperfusion leading to syncope at times. The cerebral and peripheral vascular systems probably operate to maintain cerebral oxygenation against SVT‐induced hypoperfusion. However, time courses of cerebral and peripheral oxygenation responses to SVT has not been fully understood. The aim of this study was to examine the time course and relationship between cerebral and peripheral oxygenation responses and SVT‐induced hypotension. Prefrontal and forearm tissue oxygen index (TOI) and normalized tissue hemoglobin index (nTHI) were collected by near‐infrared spectroscopy (NIRS) during electrophysiological study (EPS) in 14 patients (55 ± 4 years old, 9 men) with SVT. AP decreased during 2–20 s of SVT. The prefrontal TOI and nTHI began to decrease (P < 0.05) transiently at 6 s of SVT and then returned to the baseline level from 14 s. The initial decrease of prefrontal TOI appears to occur when hypotension was over approximately 20 mmHg. In contrast, the forearm TOI and nTHI decreased continuously from 11 s (P < 0.05). The AP and prefrontal NIRS responses suggest that SVT‐induced great hypotension (>20 mmHg) caused the transient reduction of cerebral oxygenation and blood volume, which may be followed by a recovering process owing to cerebral vasodilatation. The continuous reductions of forearm TOI and nTHI during SVT suggest restriction of muscle blood flow by vasoconstriction, which may contribute to redistribution of the blood to the brain.Support or Funding InformationThis research is supported by Automotive and Medical Concert Consortium (AMECC).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process.

Journal of Cardiovascular ElectrophysiologyVolume 28, Issue 10 p. 1224-1225 EP IMAGE Life-threatening aortic dissection with cardiac tamponade during catheter ablation for ventricular tachycardia originating from left coronary cusp Kenji Kuroki MD, Kenji Kuroki MD orcid.org/0000-0002-3257-8216 Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorAkira Sato MD, Akira Sato MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorFumi Yamagami MD, Fumi Yamagami MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorAkihiko Nogami MD, Akihiko Nogami MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorKazutaka Aonuma MD, Corresponding Author Kazutaka Aonuma MD kaonuma@md.tsukuba.ac.jp Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, Japan Correspondence Kazutaka Aonuma, MD, Professor of Medicine, Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan. Email: kaonuma@md.tsukuba.ac.jpSearch for more papers by this author Kenji Kuroki MD, Kenji Kuroki MD orcid.org/0000-0002-3257-8216 Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorAkira Sato MD, Akira Sato MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorFumi Yamagami MD, Fumi Yamagami MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorAkihiko Nogami MD, Akihiko Nogami MD Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, JapanSearch for more papers by this authorKazutaka Aonuma MD, Corresponding Author Kazutaka Aonuma MD kaonuma@md.tsukuba.ac.jp Department of Cardiology, Faculty of Medicine, University of Tsugkuba, Tsukuba, Japan Correspondence Kazutaka Aonuma, MD, Professor of Medicine, Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan. Email: kaonuma@md.tsukuba.ac.jpSearch for more papers by this author First published: 21 June 2017 https://doi.org/10.1111/jce.13277Citations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume28, Issue10October 2017Pages 1224-1225 RelatedInformation

LA dilatation and atrial fibrillation (AF) onset in pts with CHF .There is none study focused on wheather the incidence of AF in CHF pts with enlarged LA could be affected by electrical and/or mechanical dyssynchrony in this particular group of patients.Methods: We studied 215 consecutive patients (age 56 þ/-9 years, 132male) with CHF and LV ejection fraction 35% who underwent cardiac resynchronization treatment (CRT) at the time of implantation..We excluded pts with severe valvular disease.We examined clinical characteristics as age, gender, heart failure etiology, hypertension,diabetes mellitus, NYHA functional class , medical treatment , renal impairment ,electrocardiographic findings and echocardiographic measurements in all patients as risk factors regarding to atrial fibrillation history .Atrial fibrillation was defined as any atrial tachyarrhythmia 180 bpm and 30s documented by 12 leads electrocardiogram recordings or on holter monitor recordings and associated symptoms .A QRS prolongation >130ms with LBBB morphology in the 12 lead electrocardiogram was defined as the criterion of electrical dyssynchrony and was present in all included patients. .Echocardiographic studies were performed by an experienced sonographer using commercially available equipment .The LA volume was measured by Simpson's method from apical 2-and 4-chamber views, and LA volume index (LAVI) was calculated as LA volume/body surface area.LAVI 29mm3/m2 defined dilated LA .We also evaluated the left ventricular ejection fraction and respective volumes.In addition,we tested the left mechanical dyssynchrony .An aortic preejection delay 140 ms, an interventricular mechanical delay 40 ms (measured as the time delay between the left and right ventricular preejection intervals or delayed activation of the posterolateral LV wal) were used to demonstrate the mechanical dyssynchrony .Results: Multivariable, binary logistic regression models were built by adding variables significant in the univariate models.Variables were retained in the final multivariate models if p<0.05.After univariate analysis, the baseline variables associated with AF was NYHA class , LAVI and mechanical dyssynchrony (p<0.05).).After multivariable analysis, the only variable which was associated with AF was the magnitude of mechanical dyssynchrony (HR: 2.08 (CI: 1.10-3.79)).Conclusion: Mechanical dyssynchrony at time of CRT implant in pts with CHF was independently associated with AF.Left ventricular mechanical dyssynchrony is an important parameter to select CHF patients who are candidates for AF onset and to ensure that stroke prophylaxis may be initiated.