Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation

13301甲第4444号博士（医学）金沢大学博士論文本文Full 以下に掲載：Journal of Cardiology Epub ahead of print Japanese College of Cardiology. 共著者：Takashi Kusayama, Hiroshi Furusho, Haruka Kashiwagi, Takeshi Kato, Hisayoshi Murai, Soichiro Usui, Shuichi Kaneko, Masayuki Takamur

Skin sympathetic nerve activity and the temporal clustering of cardiac arrhythmias

BACKGROUND: Simultaneous noninvasively recorded skin sympathetic nerve activity (SKNA) and electrocardiogram (neuECG) can be used to estimate cardiac sympathetic tone. We tested the hypothesis that large and prolonged SKNA bursts are associated with temporal clustering arrhythmias. METHODS: We recorded neuECG in 10 patients (69 ± 10 years old) with atrial fibrillation (AF) episodes and in 6 patients (50 ± 13 years old) with ventricular tachycardia (VT) or fibrillation (VF) episodes. Clustering was defined by an arrhythmic episode followed within 1 minute by spontaneous recurrences of the same arrhythmia. The neuECG signals were bandpass filtered between 500-1000 Hz to display SKNA. RESULTS: There were 22 AF clusters, including 231 AF episodes from 6 patients, and 9 VT/VF clusters, including 99 VT/VF episodes from 3 patients. A total duration of SKNA bursts associated with AF was longer than that during sinus rhythm (78.9 min/hour [interquartile range (IQR) 17.5-201.3] vs. 16.3 min/hour [IQR 14.5-18.5], P = 0.022). The burst amplitude associated with AF in clustering patients was significantly higher than that in nonclustering patients (1.54 μV [IQR 1.35-1.89], n = 114, vs. 1.20 μV [IQR 1.05-1.42], n = 21, P < 0.001). The SKNA bursts associated with VT/VF clusters lasted 9.3 ± 3.1 minutes, with peaks that averaged 1.13 ± 0.38 μV as compared with 0.79 ± 0.11 μV at baseline (P = 0.041). CONCLUSION: Large and sustained sympathetic nerve activities are associated with the temporal clustering of AF and VT/VF. FUNDING: This study was supported in part by NIH grants R42DA043391 (THE), R56 HL71140, TR002208-01, R01 HL139829 (PSC), a Charles Fisch Cardiovascular Research Award endowed by Suzanne B. Knoebel of the Krannert Institute of Cardiology (TK and THE), a Medtronic-Zipes Endowment, and the Indiana University Health-Indiana University School of Medicine Strategic Research Initiative (PSC)

Cable externalization at the proximal portion of the superior vena cava coil in Riata implantable cardioverter defibrillator leads

Many Riata (St. Jude Medical, St. Paul, MN, USA) implantable cardioverter defibrillator (ICD) leads have reportedly developed cable externalization. The most likely cause of cable externalization is insulation abrasion, which often occurs at the can or between the right ventricular coil and superior vena cava (SVC) coil. We report a rare case of an adult male whose ICD lead cable was externalized at the proximal portion of the SVC coil. This lead became fixed to the wall at the subclavian vein and SVC and became bent between these adhesions. Furthermore, the motion of this lead was affected by pulsation of the aortic arch. The ICD lead might develop inside-out abrasion due to mechanical stress evoked by pulsation of the aortic arch at this site.. © 2016 Japanese College of Cardiology.Embargo Period 12 month

Skin sympathetic nerve activity and ventricular rate control during atrial fibrillation

Background: The relationship between the ventricular rate (VR) during atrial fibrillation (AF) and skin sympathetic nerve activity (SKNA) remains unclear. Objective: The purpose of this study was to test the hypothesis that SKNA bursts accelerate VR during AF. Methods: We simultaneously recorded electrocardiogram and SKNA in 8 patients (median age 66.0 years [interquartile range {IQR} 59.0-77.0 years]; 4 men [50%]) with 30 paroxysmal AF episodes (all >10-minute long) and 12 patients (73.0 years [IQR 60.5-80.0 years]; 6 men [50%]) with persistent AF. The average amplitude of SKNA (aSKNA [μV]) during AF was analyzed in 1-minute windows and binned, showing 2 Gaussian distributions. We used the mean + 3SD of the first Gaussian distribution as the threshold that separates burst from baseline (nonburst) SKNA. All 1-minute aSKNA values above the threshold were detected, and the area between aSKNA and baseline of every 1 minute was calculated and added as burst area. Results: VR was higher during SKNA bursts than during the nonburst period (103 beats/min [IQR 83-113 beats/min] vs 88 beats/min [IQR 76-101 beats/min], respectively; P = .003). In the highest quartile of the burst area during persistent AF, the scatterplot of maximal aSKNA and VR during each SKNA burst shows higher aSKNA and VR. The overall estimate of the correlation between maximal VR and aSKNA during bursts show a positive correlation in the highest quartile of the burst area (0.64; 95% confidence interval 0.54-0.74; P < .0001). Conclusion: SKNA bursts are associated with VR acceleration. These SKNA bursts may be new therapeutic targets for rate control during AF

Neural Mechanisms and Therapeutic Opportunities for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous system (ANS) plays a central role in AF, with the heart regulated by both extrinsic and intrinsic properties. In the extrinsic ANS, the sympathetic fibers are derived from the major paravertebral ganglia, especially the stellate ganglion (SG), which is a source of cardiac sympathetic innervation since it connects with multiple intrathoracic nerves and structures. The major intrinsic ANS is a network of axons and ganglionated plexi that contains a variety of sympathetic and parasympathetic neurons, which communicate with the extrinsic ANS. Simultaneous sympathovagal activation contributes to the development of AF because it increases calcium entry and shortens the atrial action potential duration. In animal and human studies, neuromodulation methods such as electrical stimulation and renal denervation have indicated potential benefits in controlling AF in patients as they cause SG remodeling and reduce sympathetic outflow. This review focuses on the neural mechanisms relevant to AF and the recent developments of neuromodulation methods for AF control

Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice

Selenoprotein P (SeP), a liver-derived secretory protein, functions as a selenium supply protein in the body. SeP has been reported to be associated with insulin resistance in humans through serial analysis of gene expression. Recently, SeP has been found to inhibit vascular endothelial growth factor-stimulated cell proliferation in human umbilical vein endothelial cells, and impair angiogenesis in a mouse hind limb model. In this study, the role of SeP in ischemia/reperfusion (I/R) injury has been investigated. SeP knockout (KO) and littermate wild-type (WT) mice were subjected to 30 min of myocardial ischemia followed by 24 h of reperfusion. The myocardial infarct area/area at risk (IA/AAR), evaluated using Evans blue (EB) and 2,3,5-triphenyltetrazolium chloride (TTC) staining, was significantly smaller in SeP KO mice than in WT mice. The number of terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei was significantly lower in SeP KO mice than in WT mice. In addition, caspase-3 activation was reduced in SeP KO mice compared to that in WT mice. Furthermore, phosphoinositide 3-kinase/Akt and Erk levels were examined for the reperfusion injury salvage kinase (RISK) pathway. Interestingly, SeP KO significantly increased the phosphorylation of IGF-1, Akt, and Erk compared to that in WT mice after I/R. Finally, I/R-induced myocardial IA/AAR was significantly increased in SeP KO mice overexpressing SeP in the liver compared to other SeP KO mice. These results, together, suggest that inhibition of SeP protects the heart from I/R injury through upregulation of the RISK pathway