Publications by authors named "Satoshi Higa"

62 Publications

Diabetes and Endocrine Disorders (Hyperthyroidism/Hypothyroidism) as Risk Factors for Atrial Fibrillation.

Card Electrophysiol Clin 2021 03 8;13(1):63-75. Epub 2021 Jan 8.

Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan.

Risk factors including cardiometabolic and endocrine disorders have a significant impact on atrial remodeling causing atrial fibrillation (AF). Diabetes mellitus and hyperthyroidism are strong independent risk factors for AF and worsen outcomes of rhythm control strategies. An early diagnosis and intervention for these risk factors combined with rhythm control strategies may improve the overall cardiovascular mortality and morbidity. This review summarizes the current state of knowledge about the AF risk factors diabetes mellitus and thyroid disease, and discusses the impact of the modification of these risk factors on primary and secondary prevention of AF.
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http://dx.doi.org/10.1016/j.ccep.2020.11.005DOI Listing
March 2021

ZFHX3 knockdown dysregulates mitochondrial adaptations to tachypacing in atrial myocytes through enhanced oxidative stress and calcium overload.

Acta Physiol (Oxf) 2020 Dec 17:e13604. Epub 2020 Dec 17.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Aim: To investigate the role of zinc finger homeobox 3 gene (ZFHX3) in tachypacing-induced mitochondrial dysfunction and explore its molecular mechanisms and potential as a therapeutic target in atrial fibrillation (AF).

Methods: Through a bioluminescent assay, a patch clamp, confocal fluorescence and fluorescence microscopy, microplate enzyme activity assays and Western blotting, we studied ATP and ADP production, mitochondrial electron transfer chain complex activities, ATP-sensitive potassium channels (I ), mitochondrial oxidative stress, Ca content, and protein expression in control and ZFHX3 knockdown (KD) HL-1 cells subjected to 1 and 5-Hz pacing for 24 hours.

Results: Compared with 1-Hz pacing, 5-Hz pacing increased ATP and ADP production, I , phosphorylated adenosine monophosphate-activated protein kinase and inositol 1,4,5-triphosphate (IP ) receptor (IP R) protein expression. Tachypacing induced mitochondrial oxidative stress and Ca overload in both cell types. Furthermore, under 1- and 5-Hz pacing, ZFHX3 KD cells showed higher I , ATP and ADP production, mitochondrial oxidative stress and Ca content than control cells. Under 5-Hz pacing, 2-aminoethoxydiphenyl borate (2-APB; 3 μmol/L, an IP R inhibitor) and MitoTEMPO (10 µmol/L, a mitochondria-targeted antioxidant) reduced ADP and increased ATP production in both cell types; however, only 2-APB significantly reduced mitochondrial Ca overload in control cells. Under 5-Hz pacing, mitochondrial oxidative stress was significantly reduced by both MitoTEMPO and 2-APB and only by 2-APB in control and ZFHX3 KD cells respectively.

Conclusion: ZFHX3 KD cells modulate mitochondrial adaptations to tachypacing in HL-1 cardiomyocytes through Ca overload, oxidative stress and metabolic disorder. Targeting IP R signalling or oxidative stress could reduce AF.
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http://dx.doi.org/10.1111/apha.13604DOI Listing
December 2020

Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway.

Cardiovasc Drugs Ther 2020 Sep 18. Epub 2020 Sep 18.

Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Sec- 2, Shih-Pai Road, Taipei, Taiwan.

Purpose: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model.

Methods: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4 T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation.

Results: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4 T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated.

Conclusions: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.
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http://dx.doi.org/10.1007/s10557-020-07072-zDOI Listing
September 2020

Concurrent increases in post-pacing action potential duration and contractility predict occurrence of ventricular arrhythmia.

Pflugers Arch 2020 12 14;472(12):1783-1791. Epub 2020 Aug 14.

Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road, Sec. 3, Taipei, Taiwan.

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD, p < 0.001) and contractility (ΔContractility, p = 0.003) compared with group 2. Triggered VT episodes were common (72.7%) in cases with a ΔAPD > 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na-Ca exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.
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http://dx.doi.org/10.1007/s00424-020-02445-7DOI Listing
December 2020

Editorial to "Diverse activation patterns during persistent atrial fibrillation by non-contact charge-density mapping of human atrium".

Authors:
Satoshi Higa

J Arrhythm 2020 Aug 27;36(4):703-704. Epub 2020 May 27.

Cardiac Electrophysiology and Pacing Laboratory Division of Cardiovascular Medicine Makiminato Central Hospital Okinawa Japan.

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http://dx.doi.org/10.1002/joa3.12373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411186PMC
August 2020

Resistin as a Biomarker for the Prediction of Left Atrial Substrate and Recurrence in Patients with Drug-Refractory Atrial Fibrillation Undergoing Catheter Ablation.

Int Heart J 2020 May 15;61(3):517-523. Epub 2020 May 15.

Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital.

Resistin is an adipocytokine that is abundantly secreted from lipid cells and is related to the inflammatory process and cardiometabolic diseases. This study aimed to examine the role of resistin on inflammation and its effect on the clinical outcome of patients with atrial fibrillation (AF) following catheter ablation.A total of 108 patients (56.9 ± 12.0 years, 76.8% male) with symptomatic and drug-refractory AF undergoing catheter ablation were enrolled. Inflammatory biomarkers and epicardial fat volume by contrast computed tomography (CT) images were assessed in all patients before the procedure. Baseline resistin correlated with epicardial fat volume, tumor necrosis factor-α (TNF-α), and left atrial (LA) scar area. After the index procedure, the univariate analysis revealed that hypertension, persistent AF, LA diameter, and plasma resistin level were related to recurrent atrial arrhythmia. Multivariate regression analysis revealed that persistent AF, LA diameter, and plasma resistin level all independently predicted recurrent atrial arrhythmia after ablation. Plasma resistin with a level higher than 777 (pg/mL) could predict recurrence following catheter ablation of AF.High plasma resistin level is associated with poor left atrial substrate, high epicardial fat volume, and elevated TNF-α level in patients with AF. Plasma resistin may predict the recurrence of atrial arrhythmia after ablation.
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http://dx.doi.org/10.1536/ihj.19-680DOI Listing
May 2020

The AMP-activated protein kinase modulates hypothermia-induced J wave.

Eur J Clin Invest 2020 Jun 15;50(6):e13247. Epub 2020 May 15.

Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

Background: The mechanism underlying the occurrence of the J wave in low temperature remains unclear. However, low temperature is associated with metabolic disorder and 5' AMP-activated protein kinase (AMPK), which modulates ionic currents and cardiac metabolism. This study investigated whether AMPK regulation can modulate the occurrence of the J wave at low temperature.

Methods: Unipolar and bipolar leads were used to record monophasic action potential (the endocardium and epicardium) and pseudo-electrocardiograms (inferior leads) to study the cardiac electrical activity. Measurements were taken in isolated Langendorff rabbit hearts at both 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, I , 50 µmol L ), PF06409577 (an AMPK activator, 1 µmol L ), compound C (an AMPK inhibitor, 10 µmol L ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, I , 20 µmol L ).

Results: The amplitude of the J wave (2.46 ± 0.34 mV vs. 1.11 ± 0.23 mV, P < .01) at 30℃ (n = 15) was larger than that at 37℃ (n = 15). PF06409577 (1 µmol L ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10 µmol L ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50 µmol L ) and glibenclamide (20 µmol L ).

Conclusions: AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating I and I channels.
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http://dx.doi.org/10.1111/eci.13247DOI Listing
June 2020

Catheter Ablation of Paroxysmal Atrial Fibrillation Originating from Non-pulmonary Vein Areas.

Arrhythm Electrophysiol Rev 2018 Dec;7(4):273-281

Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital Taipei, Taiwan.

Pulmonary veins (PVs) are a major source of ectopic beats that initiate AF. PV isolation from the left atrium is an effective therapy for the majority of paroxysmal AF. However, investigators have reported that ectopy originating from non-PV areas can also initiate AF. Patients with recurrent AF after persistent PV isolation highlight the need to identify non-PV ectopy. Furthermore, adding non-PV ablation after multiple AF ablation procedures leads to lower AF recurrence and a higher AF cure rate. These findings suggest that non-PV ectopy is important in both the initiation and recurrence of AF. This article summarises current knowledge about the electrophysiological characteristics of non-PV AF, suitable mapping and ablation strategies, and the safety and efficacy of catheter ablation of AF initiated by ectopic foci originating from non-PV areas.
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http://dx.doi.org/10.15420/aer.2018.50.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304799PMC
December 2018

Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure.

J Mol Cell Cardiol 2018 09 8;122:69-79. Epub 2018 Aug 8.

Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Background: We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied.

Methods And Results: The level of inflammation and Th17 cell (CD4IL-17) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti-IL-17 neutralizing antibody abolished the effects of IL-17.

Conclusions: The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF.
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http://dx.doi.org/10.1016/j.yjmcc.2018.08.005DOI Listing
September 2018

Factor Xa inhibitors differently modulate electrical activities in pulmonary veins and the sinoatrial node.

Eur J Pharmacol 2018 Aug 3;833:462-471. Epub 2018 Jul 3.

Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Factor Xa inhibitors reduce stroke in patients with atrial fibrillation. Pulmonary veins (PVs) and the sinoatrial node (SAN) are crucial for genesis of atrial fibrillation. However, the electrophysiological effects of factor Xa inhibitors (edoxaban and rivaroxaban) on PVs and the SAN remain unclear. Conventional microelectrodes were used to record the action potential in isolated rabbit PVs and SAN preparations before and after administration of edoxaban (0.1, 0.3, and 1 μM) or rivaroxaban (0.01, 0.03, 0.1, and 0.3 μM). A whole-cell patch-clamp was used to record the late sodium current (I) in isolated single rabbit PV cardiomyocytes. Edoxaban significantly reduced PV spontaneous beating rates at 0.3 and 1 μM (N = 6 rabbits, P < 0.05), and reduced SAN beating rates at 1 μM (N = 6, P < 0.05). Similarly, rivaroxaban reduced PV spontaneous beating rates at 0.1 and 0.3 μM (N = 7, P < 0.05), and reduced SAN beating rates at 0.3 μM (N = 6, P < 0.05). However, neither edoxaban (1 μM) nor rivaroxaban (0.3 μM) reduced PV spontaneous beating rates in the presence of 1 μM BMS200261 (an inhibitor of protease-activated receptors type 1, PAR1 inhibitor) or 10 μM ranolazine (an inhibitor of late sodium current, I inhibitor). Edoxaban (0.3 and 1 μM) and rivaroxaban (0.1 and 0.3 μM) respectively decreased the I by 47%, 47%, 36%, and 49% (n = 9 PV cardiomyocytes from 5 rabbits, P < 0.05). In conclusion, Factor Xa inhibitors reduce PV spontaneous activities and may modulate occurrence of atrial fibrillation by inhibiting PAR1 and reducing the I in PVs.
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http://dx.doi.org/10.1016/j.ejphar.2018.07.003DOI Listing
August 2018

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure.

J Am Heart Assoc 2018 01 22;7(2). Epub 2018 Jan 22.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Myocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction.

Methods And Results: HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF-RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF-RDN. Left anterior descending coronary artery in HF and HF-RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real-time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF-RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF-RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3-kinase, AKT, and endothelial nitric oxide synthase in HF-RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF-RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF-RDN compared with HF (50% versus 100%, <0.05).

Conclusions: RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase signaling pathway.
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http://dx.doi.org/10.1161/JAHA.117.007312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850156PMC
January 2018

Risk of Stroke in Patients With Short-Run Atrial Tachyarrhythmia.

Stroke 2017 12 16;48(12):3232-3238. Epub 2017 Nov 16.

From the Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (S.Y., C.-Y.L., S.-L.C., T.-F.C., Y.-J.L., L.-W.L., F.-P.C., Y.-F.H., T.-C.T., J.-N.L., A.L.D.T., Y.-T.C., T.-Y.C., C.-I.W., S.-A.C.); Department of Cardiovascular Medicine, Fukushima Medical University, Japan (S.Y.); Institution of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (S.-L.C., T.-F.C., Y.-J.L., L.-W.L., F.-P.C., Y.-F.H., T.-C.T., J.-N.L., S.-A.C.); Department of Medicine, Taipei Veterans General Hospital, Yuan-Shan Branch, Yilan, Taiwan (C.-Y.L.); and Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa, Japan (S.H.).

Background And Purpose: The risk of stroke in patients with short-run atrial tachyarrhythmia (AT) remains unclear. This study aimed to investigate the relationship between short-run AT and the stroke and the use of the CHADS-VASc score for the risk stratification.

Methods: From the registry of 24-hour Holter monitoring, 5342 subjects without known atrial fibrillation or stroke were enrolled. Short-run AT was defined as episodes of supraventricular ectopic beats <5 seconds.

Results: There were 1595 subjects (29.8%) with short-run AT. During the median follow-up period of 9.0 years, 494 subjects developed new-onset stroke. Patients with short-run AT had significantly higher stroke rates compared with patients without short-run AT (11.4% versus 8.3%; <0.001). In patients with short-run AT, the number of strokes per 100 person-years for patients with CHADS-VASc score of 0 and 1 were 0.23 and 0.67, respectively. However, the number of them for patients with CHADS-VASc score of 2, 3, 4, and ≥5 were 1.62, 1.89, 1.30, and 2.91, respectively. In patients with CHADS-VASc score of 0 or 1, age (>61 years old) and burden of premature atrial contractions (>25 beats/d) independently predicted the risk of stroke. In subgroup analyses, short-run AT patients were divided into 3 groups based on their CHADS-VASc scores: low score (score of 0 [men] or 1 [women]; n=324), intermediate score (score of 1 [men] or 2 [women]; n=275), and high score (score of ≥2 [men] or ≥3 [women]; n=996). When compared with low score, intermediate and high scores were independent predictors for stroke (hazard ratio, 6.165; <0.001 and hazard ratio, 8.577; <0.001, respectively).

Conclusions: Short-run AT increases the risk of stroke. Therefore, the CHADS-VASc score could be used for the risk stratification. Age and burden of premature atrial contractions were independent predictors for stroke in patients with CHADS-VASc score of 0 or 1.
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http://dx.doi.org/10.1161/STROKEAHA.117.018475DOI Listing
December 2017

Superior Rhythm Discrimination With the SmartShock Technology Algorithm - Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial.

Circ J 2017 Aug 20;81(9):1272-1277. Epub 2017 Apr 20.

Department of Heart Rhythm Management, University of Occupational and Environmental Health Japan.

Background: Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034).

Conclusions: Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.
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http://dx.doi.org/10.1253/circj.CJ-16-1330DOI Listing
August 2017

The use of a novel signal analysis to identify the origin of idiopathic right ventricular outflow tract ventricular tachycardia during sinus rhythm: Simultaneous amplitude frequency electrogram transformation mapping.

PLoS One 2017 10;12(3):e0173189. Epub 2017 Mar 10.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Introduction: The signal characteristics of intracardiac bipolar electrograms at the origin of idiopathic RVOT-VT during sinus rhythm remain unclear.

Objective: The study sought to develop a novel real-time/online technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to quantify and localize the diseased ventricular substrate in idiopathic RVOT-VT.

Methods: We retrospectively investigated the intracardiac bipolar recordings in 70 consecutive patients (26% male, mean age 42±12 years) who underwent successful radiofrequency catheter ablation of idiopathic RVOT-VT. We quantified the extent of the frequency fraction of ventricular potentials during sinus rhythm or ventricular pacing using a novel formula, the product of instantaneous amplitude and frequency, and showed that in a 3D geometry as an online SAFE-T map.

Results: The characteristics of the HHT spectra of electrograms derived from VT origins demonstrated high frequency components (>70 Hz), which were independent of the rhythm. The density of the abnormal potentials at the VT origins were higher (VT origins, 7.5±2.3 sites/cm2 vs. surrounding myocardium, 1.5±1.3 sites/cm2, p<0.001), and were significantly decreased after ablation (0.7±0.6 sites/cm2, p<0.001). A small region of abnormal potentials were observed in the VT origins (mean area of 1.5±0.8 cm2). The SAFE-T maps predicted the VT origins with 92% sensitivity, 78% specificity with optimal cut-off value of >3.0 Hz·mV.

Conclusion: The online SAFE-T map was feasible for quantifying the diseased ventricular substrate, irrespective of the rhythm of activation, and can be used to identify the optimal ablation targets for idiopathic RVOT-VT. We found a limited region of abnormal potentials where the RVOT-VT origins were successfully ablated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173189PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345764PMC
September 2017

The Different Substrate Characteristics of Arrhythmogenic Triggers in Idiopathic Right Ventricular Outflow Tract Tachycardia and Arrhythmogenic Right Ventricular Dysplasia: New Insight from Noncontact Mapping.

PLoS One 2015 21;10(10):e0140167. Epub 2015 Oct 21.

Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.

Background: The aim of this study was to investigate the different substrate characteristics of repetitive premature ventricular complexed (PVC) trigger sites by the non-contact mapping (NCM).

Methods: Thirty-five consecutive patients, including 14 with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) and 21 with idiopathic right ventricular outflow tract tachycardia (RVOT VT), were enrolled for electrophysiological study and catheter ablation guided by the NCM. Substrate and electrogram (Eg) characteristics of the earliest activation (EA) and breakout (BO) sites of PVCs were investigated, and these were confirmed by successful PVC elimination.

Results: Overall 35 dominant focal PVCs were identified. PVCs arose from the focal origins with preferential conduction, breakout, and spread to the whole right ventricle. The conduction time and distance from EA to BO site were both longer in the ARVC than the RVOT group. The conduction velocity was similar between the 2 groups. The negative deflection of local unipolar Eg at the EA site (EA slope3,5,10ms values) was steeper in the RVOT, compared to ARVC patients. The PVCs of ARVC occurred in the diseased substrate in the ARVC patients. More radiofrequency applications were required to eliminate the triggers in ARVC patients.

Conclusions/interpretation: The substrate characteristics of PVC trigger may help to differentiate between idiopathic RVOT VT and ARVC. The slowing and slurred QS unipolar electrograms and longer distance from EA to BO in RVOT endocardium suggest that the triggers of ARVC may originate from mid- or sub-epicardial myocardium. More extensive ablation to the trigger site was required in order to create deeper lesions for a successful outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140167PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619190PMC
June 2016

Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation.

Heart Rhythm 2015 May 30;12(5):1046-56. Epub 2015 Jan 30.

Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Background: Resveratrol has shown benefits in reducing ventricular remodeling and arrhythmias.

Objective: This study aimed to assess the therapeutic efficacy of resveratrol in reducing atrial fibrillation (AF) in a heart failure (HF) model and to explore the underlying mechanisms.

Methods: HF rabbits were created 4 weeks after undergoing coronary ligation. Group 1 (n = 6) was divided into subgroups of (a) normal rabbits, (b) HF sham rabbits, and (c) HF rabbits treated for 1 week with intraperitoneal injections of resveratrol, (d) resveratrol plus wortmannin, or (e) resveratrol plus diphenyleneiodonium chloride (DPI). All rabbits underwent epicardial catheter stimulation. Collagen content, messenger RNA and protein expression in ion channels, and phosphoinositide 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling pathways were studied in left atrial appendage (LAA) preparations. To investigate acute drug effects on left atrial electrophysiology, groups 2 a through 2e (n = 6 per group) were subjected to Langendorff perfusion.

Results: Higher AF inducibility was found in the HF group and groups that were given PI3K and eNOS inhibitors than in the normal and resveratrol-treated groups (P < .001). Histologic analysis of the LAA revealed a decrease in fibrosis in resveratrol-treated groups compared with the HF group (8.95% ± 1.53% vs 26.62% ± 2.19%, P < .001). In real-time polymerase chain reaction analysis, ion channels including Kv1.4, Kv1.5, KvLQT1, Kir2.1, Nav1.5, Cav1.2, NCX, SERCA2a, and phospholamban were upregulated by resveratrol. PI3K, AKT, and eNOS messenger RNA and protein expression were upregulated by resveratrol but were inhibited by the coadministration of wortmannin and DPI.

Conclusion: Resveratrol decreases left atrial fibrosis and regulates variation in ion channels to reduce AF through the PI3K/AKT/eNOS signaling pathway.
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http://dx.doi.org/10.1016/j.hrthm.2015.01.044DOI Listing
May 2015

Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart.

Int J Cardiol 2013 Oct 19;168(4):4019-26. Epub 2013 Jul 19.

Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Geranylgeranylacetone (GGA) has been reported up-regulating heat shock protein (HSP) expression, and protecting against atrial remodeling. This study aimed to investigate the effects of GGA on atrial electrophysiology and inducibility of atrial fibrillation (AF) in heart failure (HF) model.

Methods And Results: HF rabbits were created 4 weeks after coronary artery ligation. Monophasic action potential recordings and multielectrode array were used to record the electrophysiological characteristics of left atrium (LA) in normal, or HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200 mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to normal LA (n = 10) had a shorter action potential duration (APD) and effective refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of restitution curve of APD (0.94 ± 0.04 vs.1.69 ± 0.04, P < 0.001), and less inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a shorter activation time and higher conduction velocity than HF-control LA. HF-GGA LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1, sarcoplasmic reticulum Ca(2+)-ATPase, and higher phosphorylation of phospholamban than HF-control LA.

Conclusions: GGA decreases triggered activity, dispersion of APD and inducibility of AF in failing heart through induction of HSP, and modulation of ionic channels and calcium homeostasis.
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http://dx.doi.org/10.1016/j.ijcard.2013.06.072DOI Listing
October 2013

Effective prediction of response to cardiac resynchronization therapy using a novel program of gated myocardial perfusion single photon emission computed tomography.

Europace 2011 Dec 25;13(12):1731-7. Epub 2011 Aug 25.

Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.

Aims: The limitation of QRS duration as a surrogate measure for left ventricular (LV) mechanical dyssynchrony (LVMD) in cardiac resynchronization therapy (CRT) patient selection encourages seeking alternatives to QRS duration. Exploring the potential of an analysis program of electrocardiographically gated myocardial perfusion single photon emission computed tomography (SPECT) (GMPS) for the estimation of LVMD to predict CRT response.

Methods And Results: Twenty-four patients undergoing CRT for advanced heart failure caused by non-ischaemic cardiomyopathy were studied. Gated myocardial perfusion single photon emission computed tomographies were performed in the setting of temporary CRT suspension after 1 week of CRT adoption. The GMPS data were computed with a novel program capable of segmental LV time-volume analysis. When a brain natriuretic peptide (BNP) value decreased >50% at 6-month follow-up, the patient was defined as a CRT responder. Receiver operating characteristic (ROC) curves for identification of responders were analysed for standard deviation of time to end systole (TES-SD) among 17 LV segments. Linear regression analyses demonstrated that an increase in percentage reduction in BNP level at 6-month follow-up was predicted by an increase in TES-SD (R(2) = 0.21, P = 0.023). The TES-SD in responders (n = 15, 62.5%) was higher than that in non-responders (100 ± 51 vs. 41 ± 17 ms, P = 0.0008). A cutoff value of TES-SD >49 ms predicted responders with 100% sensitivity and 78.8% specificity and the area under the ROC curve was 0.881 for TES-SD (P = 0.002).

Conclusions: The estimation of LVMD using this novel GMPS program could be an alternative or a complementary approach to QRS duration in CRT patient selection. This finding warrants further assessment of our approach in larger studies.
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http://dx.doi.org/10.1093/europace/eur143DOI Listing
December 2011

Impact of pacing and high-pass filter settings on ventricular bipolar electrograms in implantable cardioverter defibrillator systems. - Implication of predictors for inappropriate therapy caused by oversensing of repolarization electrograms-.

Circ J 2011 14;75(9):2095-104. Epub 2011 Jul 14.

Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

Background: Predictors of T wave oversensing with implantable cardioverter-defibrillator (ICD) systems remains to be clarified.

Methods And Results: Thirteen consecutive patients who underwent ICD implantations were included. The depolarization (R) and repolarization (T) of bipolar electrograms during baseline, AAI and DDD modes, and an isoproterenol (ISO) infusion were evaluated. The R wave amplitude during DDD was significantly lower as compared to that during the other conditions in all high-pass filter settings. In contrast, there was no significant difference in the T wave amplitude during the DDD as compared to the other conditions. With the DDD, there was a significantly higher incidence of a T/R ratio of greater than 0.25 as compared to that with the other conditions. T wave amplitude in Brugada syndrome was significantly higher than that in non-Brugada syndrome. The existence of Brugada syndrome and T/R ratio during the AAI with a high-pass filter setting of 10/20 Hz was an excellent predictor of T wave oversensing in the follow-up period.

Conclusions: DDD had a significant impact on the R wave amplitude reduction and the T/R ratio during AAI can be predictors of T wave oversensing. These findings have important implications for inappropriate shocks due to T wave oversensing.
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http://dx.doi.org/10.1253/circj.cj-11-0200DOI Listing
December 2011

The correlation between ventricular repolarization and clinical severity of spinal cord injuries.

Heart Rhythm 2011 Jun 26;8(6):879-84. Epub 2011 Jan 26.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Alteration in ventricular repolarization has been reported in patients with spinal cord injuries (SCIs). However, its clinical impact remains unclear.

Objective: The purpose of this study was to investigate the correlation between SCIs and ventricular repolarization and the associated clinical impact.

Methods: One hundred forty-four patients with an SCI were retrospectively reviewed and were divided into two groups (SCI level ≤ T6, n = 110; SCI level >T6, n = 34). The electrocardiograms were reviewed during acute phase (at emergency room) and chronic phase (>1 year).

Results: There were no differences in the underlying diseases or in ASIA score between the two groups, except there were more patients with tetraplegia among those with an SCI level ≤ T6. For the electrophysiological parameters from the electrocardiograms, the patients with an SCI level ≤ T6 had longer QTc and PR interval than those with an SCI level >T6 during acute phase. In the chronic phase, there were no differences in the electrophysiological parameters between the two groups. Only in patients with an SCI level ≤ T6 did a Kaplan-Meier analysis show that QTc prolongation could predict 30-day mortality after the acute injury. After multivariate Cox regression analysis, only tetraplegia and QTc prolongation were independent predictors of 30-day mortality (odds ratios 7.85 and 34.62, respectively). In patients with an SCI level ≤ T6, the QTc intervals were shorter in the chronic phase than those during the acute phase.

Conclusion: QTc interval was associated with the level of acute SCI and predicted the 30-day mortality.
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http://dx.doi.org/10.1016/j.hrthm.2011.01.034DOI Listing
June 2011

Different patterns of atrial remodeling after catheter ablation of chronic atrial fibrillation.

J Cardiovasc Electrophysiol 2011 Apr 13;22(4):385-93. Epub 2010 Oct 13.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Multiple remodeling patterns have been observed after catheter ablation of atrial fibrillation (AF).

Objective: We aimed to clarify the electrical/structural properties associated with recurrences after ablation of chronic AF.

Methods: After a stepwise ablation procedure in 120 consecutive patients with persistent/long-lasting persistent AF, 36 had a recurrence of AF (Group 1/Group 2: recurrence with paroxysmal/persistent AF, n = 16/20).

Results: During the first procedure, the left atrial (LA) bipolar voltage did not differ between the 2 groups, and the LA volume was smaller in Group 1 than in Group 2 and it was the only factor predicting the recurrent types (P = 0.009, OR = 1.04). In the second procedure, the bipolar voltage of the global left atrium increased (1.33 ± 0.11 mV vs 1.76 ± 0.16 mV, P = 0.001) in Group 1 and decreased (1.31 ± 0.14 mV vs 0.90 ± 0.12 mV, P = 0.01) in Group 2, when compared with that of the first procedure. The LA low-voltage area (<0.5 mV) decreased in Group 1, and increased in Group 2. The LA volume (90 ± 8 cm(3) vs 72 ± 8 cm(3), P = 0.002) decreased in the second procedure in Group 1. It remained the same in Group 2. The right atrial substrates did not change between the procedures. After a follow-up of 27 ± 3 months, all patients in Group 1 and 14 patients in Group 2 remained in sinus rhythm (P = 0.02).

Conclusion: A better outcome with reverse electrical and structural remodeling occurred after the ablation of chronic AF when the recurrence was paroxysmal AF. Progressive electrical remodeling without any structural remodeling developed in those with a recurrence involving persistent AF.
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http://dx.doi.org/10.1111/j.1540-8167.2010.01927.xDOI Listing
April 2011

The novel electrophysiology of complex fractionated atrial electrograms: insight from noncontact unipolar electrograms.

J Cardiovasc Electrophysiol 2010 Jun 28;21(6):640-8. Epub 2009 Dec 28.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The noncontact mapping (NCM) system possesses the merit of global endocardial recording for unipolar and activation mapping.

Objective: We aimed to evaluate the unipolar electrogram characteristics and activation pattern over the bipolar complex fractionated atrial electrogram (CFAE) sites during atrial fibrillation (AF).

Methods: Twenty patients (age 55 +/- 11 years old, 15 males) who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were included. Both contact bipolar (32-300 Hz) and NCM virtual unipolar electrograms (0.5-300 Hz) were simultaneously recorded along with the activation pattern (total 223 sites, 11 +/- 4 sites/patient). A CFAE was defined as a mean bipolar cycle length of
Results: The Group 1A CFAE sites exhibited a shorter unipolar electrogram cycle length (129 +/- 11 vs 164 +/- 20 ms, P < 0.001), and higher percentage of an S-wave predominant pattern (QS or rS wave, 63 +/- 13% vs 35 +/- 13%, P < 0.001) than the Group 2 non-CFAE sites. There was a linear correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87). Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%) or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs exhibited a passive activation (44%) or slow conduction (31%).

Conclusions: The bipolar repetitive and continuous fractionated CFAEs represented different activation patterns. The former was associated with an S wave predominant unipolar morphology which may represent an important focus for maintaining AF.
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http://dx.doi.org/10.1111/j.1540-8167.2009.01679.xDOI Listing
June 2010

The disparities in the electrogram voltage measurement during atrial fibrillation and sinus rhythm.

J Cardiovasc Electrophysiol 2010 Apr 10;21(4):393-8. Epub 2009 Nov 10.

Division of Cardiology, Tung's Taichung Metroharbour Hospital, Taichung, Taiwan.

Introduction: The peak electrogram voltage is a typical metric applied at each site for voltage mapping. However, the peak amplitude depends on the direction and complexity of the wavefront propagation. The root-mean-square (RMS) measure of the amplitude is a temporal integral that represents the steady-state value. The objective of this study was to investigate the disparities between the electrogram voltage during SR and AF by using 2 recording modalities: the conventional peak voltage and an RMS measurement.

Methods And Results: This study enrolled 20 patients (age = 59 +/- 13) with paroxysmal AF undergoing catheter ablation guided by Ensite array. The unipolar electrogram voltage during SR and AF (7 seconds in duration) was obtained from the same sites, and labeled by the 3-dimensional (3D) geometry. Overall 1,200 electrograms were analyzed from equally distributed mapping sites in the left atrium. A point-by-point comparison of the unipolar peak negative voltage (PNV) showed less agreement (Bland and Altman test: 10.4% outside 2 standard deviations, and intraclass correlation coefficient [ICC]= 0.64). The RMS voltage demonstrated agreement between SR and AF for all sites (BA test: 5.9% of the sites, and the ICC = 0.81). The probability of predicting a low-voltage during AF using the voltage during SR was significantly lower when using the PNV measurement compared to that when using the RMS voltage (15% vs 61%, P < 0.05).

Conclusion: The peak electrogram unipolar voltage during AF did not represent the voltage during SR. The RMS amplitude may be an alternative metric for voltage mapping to characterize the myocardial substrate.
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http://dx.doi.org/10.1111/j.1540-8167.2009.01637.xDOI Listing
April 2010

Spatiotemporal organization of the left atrial substrate after circumferential pulmonary vein isolation of atrial fibrillation.

Circ Arrhythm Electrophysiol 2009 Jun 6;2(3):233-41. Epub 2009 Mar 6.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: There is a paucity of data regarding the mechanism of maintaining atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF. The aim of this study was to examine the impact of circumferential PVI on the left atrial (LA) substrate characteristics.

Methods And Results: Seventy-two AF patients (age, 53+/-11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18+/-18% and 12+/-17% of the LA sites, before and after PVI, respectively, P=0.02), degree of LA fractionation (mean fractionated interval: 75.6+/-14.3 msec versus 87.3+/-16.7 msec, P=0.001), and mean LA dominant frequencies (6.92+/-0.88 Hz versus 6.58+/-0.91 Hz, P=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%, P<0.05).

Conclusions: Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.
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http://dx.doi.org/10.1161/CIRCEP.108.812024DOI Listing
June 2009

Characteristics of complex fractionated electrograms in nonpulmonary vein ectopy initiating atrial fibrillation/atrial tachycardia.

J Cardiovasc Electrophysiol 2009 Dec;20(12):1305-12

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Nonpulmonary vein (PV) ectopy initiating atrial fibrillation (AF)/atrial tachycardia (AT) is not uncommon in patients with AF. The relationship of complex fractionated atrial electrograms (CFAEs) and non-PV ectopy initiating AF/AT has not been assessed. We aimed to characterize the CFAEs in the non-PV ectopy initiating AF/AT.

Methods: Twenty-three patients (age 53 +/- 11 y/o, 19 males) who underwent a stepwise AF ablation with coexisting PV and non-PV ectopy initiating AF or AT were included. CFAE mapping was applied before and after the PV isolation in both atria by using a real-time NavX electroanatomic mapping system. A CFAE was defined as a fractionation interval (FI) of less than 120 ms over 8-second duration. A continuous CFAE (mostly, an FI < 50 ms) was defined as electrogram fractionation or repetitive rapid activity lasting for more than 8 seconds.

Results: All patients (100%) with non-PV ectopy initiating AF or AT demonstrated corresponding continuous CFAEs at the firing foci. There was no significant difference in the FI among the PV ostial or non-PV atrial ectopy or other atrial CFAEs (54.1 +/- 5.6, 58.3 +/- 11.3, 52.8 +/- 5.8 ms, P = 0.12). Ablation targeting those continuous CFAEs terminated the AF and AT and eliminated the non-PV ectopy in all patients (100%). During a follow-up of 7 months, 22% of the patients had an AF recurrence with PV reconnections. There was no recurrence of any ablated non-PV ectopy during the follow-up.

Conclusion: The sites of the origin of the non-PV ectopies were at the same location as those of the atrial continuous CFAEs. Those non-PV foci were able to initiate and sustain AF/AT. By limited ablation targeting all atrial continuous CFAEs, the AF could be effectively eliminated.
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http://dx.doi.org/10.1111/j.1540-8167.2009.01617.xDOI Listing
December 2009

Efficacy of additional ablation of complex fractionated atrial electrograms for catheter ablation of nonparoxysmal atrial fibrillation.

J Cardiovasc Electrophysiol 2009 Jun;20(6):607-15

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Sec. 2 Shih-Pai Road, Taipei, Taiwan.

Background: The efficacy of ablation of complex fractionated atrial electrograms (CFEs) in the single ablation procedure for nonparoxysmal atrial fibrillation (AF) patients is not well demonstrated. The aim of this study was to compare the ablation strategies of pulmonary vein isolation (PVI) plus linear ablation with and without additional ablation ofCFEs in these patients.

Methods: Consecutive 60 patients (49 +/- 11 years old, 50 male, 10 female) with nonparoxysmal AF underwent catheter ablation guided by a NavX mapping system. A stepwise approach included a circumferential PVI and left atrial (LA) linear ablation followed by either the additional ablation of continuous CFEs in the LA/coronary sinus (the first 30 patients) or not (the second 30 patients), detected by an automatic algorithm.

Results: There was no difference in the baseline characteristics between the two groups. Complete PVI eliminated some continuous CFEs and altered the distribution of CFEs. Following PVI and linear ablation,the remaining continuous CFEs were identified in 7.9 +/-10% mapping sites of the LA and CS, and were ablated successfully with a procedural AF termination rate of 53%. With a follow-up of 19 +/-11 months, a Kaplan-Meier analysis showed that the patients with additional ablation of the CFEs had a higher rate of sinus rhythm maintenance. Multivariate analysis showed the single procedure success could be predicted by the procedural AF termination and the additional ablation of continuous CFEs in the LA/CS.

Conclusions: Ablation of continuous CFEs after PVI and LA linear ablation had a better long-term efficacy based on the results of single-ablation procedure.
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http://dx.doi.org/10.1111/j.1540-8167.2008.01393.xDOI Listing
June 2009

[HIV- and HHV-8-negative primary effusion lymphoma-like lymphoma presenting with lymphomatous effusions complicated by cardiac tamponade-a case report].

Gan To Kagaku Ryoho 2009 Jul;36(7):1195-8

Dept. of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine.

We report a rare case of human immunodeficiency virus (HIV)- and human herpes virus-8 (HHV-8)-negative primary effusion lymphoma (PEL)-like lymphoma presenting with lymphomatous effusions complicated by cardiac tamponade. A 68-year-old woman was hospitalized with generalized weakness in June 2006. Echocardiogram revealed the presence of pericardial effusion and she had the signs of cardiac tamponade. Urgent pericardial drainage relieved her symptoms. Chest computed tomography showed bilateral pleural effusions along with pericardial effusion. Cytologic findings of both effusions were suggestive of malignancies, including malignant lymphoma. Immunocytochemical studies with a panel of antibodies, including CD20 and CD79a, could not provide a definite diagnosis. Flow cytometric analysis of pleural effusion revealed that tumor cells were positive for CD10 and CD19, but negative for CD20, CD23, surface immunoglobulin, and T-cell associated antigens. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. Polymerase chain reaction proved to be negative for HHV-8. The serology test for HIV was negative. After a diagnosis of HHV-8-negative PEL-like lymphoma, she was treated with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone). However, she died of progressive lymphoma 7 months after the diagnosis. PEL-like lymphomas are of B-cell origin. In some cases of PEL-like lymphoma, tumor cells may be negative for representative markers of B-cell phenotype such as CD20 and CD79a.
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July 2009

The impact of left atrial size on long-term outcome of catheter ablation of chronic atrial fibrillation.

J Cardiovasc Electrophysiol 2009 Nov 13;20(11):1211-6. Epub 2009 Jul 13.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The left atrial (LA) size is an important predictor of atrial fibrillation (AF) procedural termination and the long-term outcome. We sought to evaluate the long-term outcome in regard to the LA size and procedural termination.

Methods: Eighty-seven consecutive chronic AF patients (72 males, 53 +/- 10 years) underwent 3D mapping (NavX) and ablation. A stepwise approach including circumferential pulmonary vein (PV) isolation, linear ablation, and continuous complex-fractionated electrogram (CFE) ablation (targeting fractionation intervals of < 50 ms). Electrical cardioversion was applied to those without any procedural termination. The freedom from AF was defined as the maintenance of sinus rhythm without the use of any class I or III antiarrhythmic drugs after the blanking period.

Results: Among the 87 patients, all received a circumferential PV isolation, 93% a linear ablation, and 59% a continuous CFE ablation. Those with AF procedural termination (n = 30) had a better long-term outcome when compared with those without termination during a follow-up of 21 +/- 12 months. Moreover, a Kaplan-Meier analysis showed that in those with an LA diameter of less than 45 mm (n = 49), the freedom from AF rate was higher when procedural termination was achieved (P = 0.004). On the contrary, the outcome was comparable in those with an LA diameter of >or= 45 mm (n = 38), whether AF procedural termination occurred or not (P = 0.658).

Conclusions: AF procedural termination was related to the long-term success during chronic AF ablation, especially in those with an LA diameter of less than 45 mm. The favorable effect of termination decreased when the LA diameter was >or= 45 mm.
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http://dx.doi.org/10.1111/j.1540-8167.2009.01546.xDOI Listing
November 2009

Gender differences of electrophysiological characteristics in focal atrial tachycardia.

Am J Cardiol 2009 Jul 3;104(1):97-100. Epub 2009 May 3.

Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.

Gender differences of supraventricular tachycardias such as atrioventricular nodal re-entry, atrioventricular re-entry, and atrial fibrillation have been reported. There is little evidence of the effect of gender on focal atrial tachycardia (FAT). The study consisted of 298 patients who were referred to this institution for radiofrequency catheter ablation of FAT from October 1992 to April 2008 and included 156 men (52%) and 142 women (48%). Men were significantly older than women (57.9 +/- 18.2 vs 47.2 +/- 19.0 years old, p <0.001). Women had more associated arrhythmias (17.0% vs 28.9%, p = 0.01), mostly due to an increased incidence of atrioventricular nodal re-entrant tachycardia. Men had more cardiovascular co-morbidities (19.9% vs 9.9%, p = 0.02), a mechanism of increased automaticity (19.1% vs 8.1%, p = 0.01), and nonparoxysmal tachycardia (14.7% vs 4.4%, p = 0.01). No gender differences were noted among FAT number, left atrial involvement, shortest tachycardia cycle, success rate of catheter ablation, or recurrence rate of FAT. Mean duration of follow-up was 63.2 +/- 47.5 months. Premenopausal women had a lesser cardiovascular co-morbidity (15.3% vs 4.3%, p = 0.04) and a greater incidence of a mechanism of increased automaticity (13.4% vs 2.9%, p = 0.03). In conclusion, gender differences in electrophysiologic characteristics were noted in FAT.
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http://dx.doi.org/10.1016/j.amjcard.2009.02.050DOI Listing
July 2009