Most strokes in patients with atrial fibrillation（AF）are believed to be cardioembolic, caused by the embolism of left atrial thrombi. As shown by the well-known Virchow triad, thrombus formation in the left atrium（LA）can result from decreased blood flow, increased endocardial dysfunction in the LA, and enhanced blood coagulability. We examined whether short-term rapid atrial excitation affects gene expression remotely in the liver, which is a major source of prothrombotic molecules. DNA microarray analysis revealed marked changes in the gene expression profile of human liver of patients with AF. The extrinsic prothrombin activation pathway showed the most prominent change in 354 BioCarta pathways. Twelve hours of rapid atrial pacing（RAP）also markedly altered the gene expression profile of rat liver. RAP markedly augmented the hepatic messenger RNA expression of fibrinogen chains, prothrombin, coagulation factor X, and antithrombin Ⅲ. The augmented fibrinogen production by RAP was accompanied by increased interleukin 6（IL-6）messenger RNA expression in peripheral blood cells, enhanced monocyte chemoattractant protein-1 expression in the liver, infiltrated cluster of differentiation 11b–positive mononuclear cells in the liver, and enhanced signal transducer and activator of transcription 3（STAT3）phosphorylation in the nuclei of hepatocytes. STAT3 phosphorylation and increased fibrinogen and coagulation factor X production by RAP were suppressed by IL-6 neutralizing antibody. These findings suggest the presence of cardiohepatic interaction mediated by the IL-6/STAT3 signaling pathway in AF and AF-related thromboembolism.

In Brugada syndrome（BrS）, SCN5A is found in 15 – 20％, though it is unknown whether it has a clinical impact for predicting future cardiac events. This multicenter registry enrolled 415 probands（n=403 ; men, 97％; age, 46±14 years）diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. The mean follow-up period was 72 months and the overall cardiac event rate was 2.5％/y. Probands without mutations（SCN5A（－）, n=355）experienced their first cardiac event at a younger age（34 versus 42 years, p=0.013）, had a higher positive rate of late potentials（89％ versus 73％, p=0.016）, exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events（p=0.017 by log-rank） compared to probands with SCN5A mutations（SCN5A（+）, n=60）. In multivariate analysis, only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events（SCN5A（+）versus SCN5A（－）: hazard ratio, 2.0 and p=0.045 ; history of aborted cardiac arrest versus no such history : hazard ratio, 6.5 and p＜0.001）. In conclusion, BrS patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have a higher risk for cardiac events.

An 83-year-old woman with a history of frequent paroxysmal supraventricular tachycardia underwent radiofrequency catheter ablation. Baseline electrophysiological study showed that the atrioventricular node had dual pathways and the earliest atrial activation during right ventricular pacing was located at the His-bundle（His）recording site with decremental property. Narrow QRS regular tachycardia at a cycle length（CL）of 470ms induced by atrial burst pacing was consistent with slow-fast atrioventricular nodal reentrant tachycardia（s/f AVNRT）. We ablated the slow pathway（SP）with the anatomical and electrogram-guided methods, but a tachycardiawith a similar intracardiac activation pattern to s/f AVNRT was still inducible by rapid atrial pacing during infusion of isoproterenol（ISP）with a dosage of 0.5µg/min. During the tachycardia, a premature atrial contraction（PAC）occurring when His was refractory advanced the following His, which indicated s/f AVNRT. On the other hand, an earlier PAC advanced the immediate His without termination of the tachycardia, which indicated junctional tachycardia. Although these were conflicting, the latter observation could be explained by double ventricular responses to a single PAC via the fast pathway and the SP. Therefore, further ablation for SP was continued until no tachycardia could be induced with ISP. The patient remained free from arrhythmic recurrence during the follow-up of 3 months.