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Hsiao, Ya-Wen, Tsai, Yung-Nan, Huang, Yu-Ting, Liu, Shuen-Hsin, Lin, Yenn-Jiang, Lo, Li-Wei, Hu, Yu-Feng, Chung, Fa-Po, Lin, Shien-Fong, Chang, Shih-Lin, Higa, Satoshi, and Chen, Shih-Ann
- Cardiovascular Drugs and Therapy. 35(5):889-900
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Liu, Chih-Min, Liu, Chien-Liang, Hu, Kai-Wen, Tseng, Vincent S., Chang, Shih-Lin, Lin, Yenn-Jiang, Lo, Li-Wei, Chung, Fa-Po, Chao, Tze-Fan, Tuan, Ta-Chuan, Liao, Jo-Nan, Lin, Chin-Yu, Chang, Ting-Yung, Shen-Jang Fann, Cathy, Higa, Satoshi, Yagi, Nobumori, Hu, Yu-Feng, and Chen, Shih-Ann
- Canadian journal of cardiology. 38(2):152-159
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Liu, Chih-Min, Lin, Feng-Zhi, Chen, Yao-Chang, Lin, Yung-Kuo, Lu, Yen-Yu, Wu, Cheng-I, Higa, Satoshi, Chen, Shih-Ann, and Chen, Yi-Jen
- Pflügers Archiv - European Journal of Physiology. 472(12):1783-1791
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4. Mechanism of angiotensin receptor-neprilysin inhibitor in suppression of ventricular arrhythmia [2021]
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Tsai, Yung-Nan, Cheng, Wen-Han, Chang, Yao-Ting, Hsiao, Ya-Wen, Chang, Ting-Yung, Hsieh, Yu-Cheng, Lin, Yenn-Jiang, Lo, Li-Wei, Chao, Tze-Fan, Kuo, Ming-Jen, Higa, Satoshi, Chang, Shih-Lin, and Chen, Shih-Ann
- Journal of cardiology. 78(4):275-284
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5. Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy [2023]
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Ting-I Lee, Nguyen Ngoc Trang, Ting-Wei Lee, Satoshi Higa, Yu-Hsun Kao, Yao-Chang Chen, and Yi-Jen Chen
- International Journal of Molecular Sciences, Vol 24, Iss 22, p 16142 (2023)
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arrhythmias, calcium homeostasis, diabetic cardiomyopathy, electrophysiology, ketogenic diet, Biology (General), QH301-705.5, Chemistry, and QD1-999
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A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.
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Yung-Nan Tsai, Ya-Wen Hsiao, Shien-Fong Lin, Yi-Hsin Chan, Yu-Cheng Hsieh, Wei-Hua Tang, An-Sheng Lee, Yu-Ting Huang, Hsing-Yuan Li, Tze-Fan Chao, Satoshi Higa, Tsu-Juey Wu, Shih-Lin Chang, and Shih-Ann Chen
- Frontiers in Cardiovascular Medicine, Vol 8 (2021)
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alternans, the maximum calcium transient, IL-17 neutralizer, IL-17, ventricular arrhythmias, Diseases of the circulatory (Cardiovascular) system, and RC666-701
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Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.
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Yu-Hsun Kao, Yi-Jen Chen, Satoshi Higa, Nipon Chattipakorn, and Gaetano Santulli
- Frontiers in Physiology, Vol 14 (2023)
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cardiovascular medicine, induced pluripotent stem cell (iPSC), LMNA, ZFHX3, bioengineering, cardiac arrhythmia, Physiology, and QP1-981
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8. Mechanism of angiotensin receptor-neprilysin inhibitor in suppression of ventricular arrhythmia [2021]
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Wen Han Cheng, Shih Lin Chang, Yao Ting Chang, Li Wei Lo, Yung Nan Tsai, Shih Ann Chen, Yu Cheng Hsieh, Tze Fan Chao, Ting Yung Chang, Ming Jen Kuo, Yenn Jiang Lin, Satoshi Higa, and Ya Wen Hsiao
- Journal of Cardiology. 78:275-284
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medicine.medical_specialty, Angiotensin receptor, Diastole, Tetrazoles, Angiotensin-Converting Enzyme Inhibitors, Context (language use), 030204 cardiovascular system & hematology, Sacubitril, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, cardiovascular diseases, 030212 general & internal medicine, Systole, Heart Failure, Receptors, Angiotensin, Ejection fraction, business.industry, Arrhythmias, Cardiac, Stroke Volume, medicine.disease, Treatment Outcome, Valsartan, Heart failure, cardiovascular system, Cardiology, Neprilysin, Rabbits, Cardiology and Cardiovascular Medicine, business, and medicine.drug
- Abstract
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Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.
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Chin-Yu Lin, Ting-Yung Chang, Chih Min Liu, Tze-Fan Chao, Fa Po Chung, Kai-Wen Hu, Ta-Chuan Tuan, Jo-Nan Liao, Cathy S.J. Fann, Satoshi Higa, Chien-Liang Liu, Yenn Jiang Lin, Yu-Feng Hu, Vincent S. Tseng, Li-Wei Lo, Shih Lin Chang, Nobumori Yagi, and Shih Ann Chen
- Canadian Journal of Cardiology. 38:152-159
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Adult, Male, medicine.medical_specialty, Adolescent, Taiwan, Sudden cardiac death, Electrocardiography, Young Adult, Deep Learning, Rare Diseases, Cohen's kappa, Internal medicine, medicine, Humans, Diagnosis, Computer-Assisted, cardiovascular diseases, Medical diagnosis, Brugada Syndrome, Retrospective Studies, Brugada syndrome, business.industry, Incidence, Deep learning, Middle Aged, Right bundle branch block, medicine.disease, Feature (computer vision), Cohort, Cardiology, Female, Artificial intelligence, Cardiology and Cardiovascular Medicine, business, and Follow-Up Studies
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Background Brugada syndrome is a major cause of sudden cardiac death in young people with a distinctive electrocardiogram (ECG) feature. We aimed to develop a deep learning-enabled ECG model for automatic screening Brugada syndrome to identify these patients at an early time, thus allowing for life-saving therapy. Methods A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was further validated in the independent ECG dataset, collected from the hospitals in Taiwan and Japan. Results The diagnoses by the deep learning model (AUC: 0.96, sensitivity: 88.4%, specificity: 89.1%) were highly consistent with the standard diagnoses (Kappa coefficient: 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity: 86.0%, specificity: 90.0%). Conclusions We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivaling trained physicians.
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Ya Wen Hsiao, Shuen Hsin Liu, Yenn Jiang Lin, Fa Po Chung, Shih Lin Chang, Shih Ann Chen, Yu Feng Hu, Satoshi Higa, Yung Nan Tsai, Yu Ting Huang, Li Wei Lo, and Shien-Fong Lin
- Cardiovascular Drugs and Therapy. 35:889-900
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0301 basic medicine, MAPK/ERK pathway, MAP Kinase Signaling System, p38 mitogen-activated protein kinases, Anti-Inflammatory Agents, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, Electrocardiography, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Phenols, Fibrosis, NLR Family, Pyrin Domain-Containing 3 Protein, Rhodiola, Animals, Medicine, Pharmacology (medical), RNA, Messenger, Chemokine CCL20, Dose-Response Relationship, Drug, biology, business.industry, Interleukin-17, Salidroside, Arrhythmias, Cardiac, General Medicine, medicine.disease, biology.organism_classification, CD4 Lymphocyte Count, Disease Models, Animal, Drug Combinations, 030104 developmental biology, chemistry, Apoptosis, Rabbits, Interleukin 17, Inflammation Mediators, Cardiology and Cardiovascular Medicine, business, and Signal Transduction
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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. 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. 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. 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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Cheng I. Wu, Feng Zhi Lin, Chih Min Liu, Yung Kuo Lin, Yao Chang Chen, Yen Yu Lu, Shih Ann Chen, Satoshi Higa, and Yi Jen Chen
- Pflügers Archiv - European Journal of Physiology. 472:1783-1791
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0301 basic medicine, medicine.medical_specialty, Physiology, Clinical Biochemistry, Pilsicainide, Contractility, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sodium channel blocker, Physiology (medical), Internal medicine, medicine, Repolarization, Receptor, Pacing - action, business.industry, 030104 developmental biology, chemistry, Pinacidil, cardiovascular system, Cardiology, Potassium channel opener, business, 030217 neurology & neurosurgery, and medicine.drug
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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 (ΔAPD90, p 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD90 < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na+-Ca2+ 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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Wu, Cheng-I, Lu, Yen-Yu, Chen, Yao-Chang, Lin, Feng-Zhi, Huang, Jen-Hung, Lin, Yung-Kuo, Higa, Satoshi, Chan, Chao-Shun, Liu, Chih-Min, Chen, Shih-Ann, and Chen, Yi-Jen
- European Journal of Clinical Investigation. June 2020, Vol. 50 Issue 6, pn/a, 9 p.
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Lin, Yenn-Jiang, Higa, Satoshi, Tai, Ching-Tai, Chang, Shih-Lin, Lee, Kun-Tai, Lo, Li-Wei, Ishigaki, Sugako, Tuan, Ta-Chuan, Wongcharoen, Wanwarang, Hu, Yu-Feng, Hsieh, Min-Hsiung, Tsao, Hsuan-Ming, and Chen, Shih-Ann
- In
Heart Rhythm 2009 6(5):592-598
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Chih-Min, Liu, Feng-Zhi, Lin, Yao-Chang, Chen, Yung-Kuo, Lin, Yen-Yu, Lu, Cheng-I, Wu, Satoshi, Higa, Shih-Ann, Chen, and Yi-Jen, Chen
- Pflugers Archiv : European journal of physiology. 472(12)
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Male, Phenylurea Compounds, Pinacidil, Action Potentials, Lidocaine, Tetrazoles, Heart, Myocardial Contraction, Heart Rate, Tachycardia, Ventricular, Animals, Rabbits, Anti-Arrhythmia Agents, and Sodium Channel Blockers
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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
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Chih-Min Liu, Chien-Liang Liu, Kai-Wen Hu, Vincent S. Tseng, Shih-Lin Chang, Yenn-Jiang Lin, Li-Wei Lo, Fa-Po Chung, Tze-Fan Chao, Ta-Chuan Tuan, Jo-Nan Liao, Chin-Yu Lin, Ting-Yung Chang, Cathy Shen-Jang Fann, Satoshi Higa, Nobumori Yagi, Yu-Feng Hu, and Shih-Ann Chen
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education and cardiovascular diseases
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BACKGROUND Brugada syndrome is a rare inherited arrhythmia with a unique electrocardiogram (ECG) pattern (type 1 Brugada ECG pattern), which is a major cause of sudden cardiac death in young people. Automatic screening for the ECG pattern of Brugada syndrome by a deep learning model gives us the chance to identify these patients at an early time, thus allowing them to receive life-saving therapy. OBJECTIVE To develop a deep learning-enabled ECG model for diagnosing Brugada syndrome. METHODS A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. We first trained the network to identify right bundle branch block (RBBB) pattern, and then, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was also validated by the independent international data of ECGs. RESULTS The AUC (area under the curve) of the deep learning model in diagnosing the type 1 Brugada ECG pattern was 0.96 (sensitivity: 88.4%, specificity: 89.1%). The sensitivity and specificity of the cardiologists for the diagnosis of the type 1 Brugada ECG pattern were 62.7±17.8%, and 98.5±3.0%, respectively. The diagnoses by the deep learning model were highly consistent with the standard diagnoses (Kappa coefficient: 0.78, McNemar test, P = .86). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.60, McNemar test, P = 2.35x10-22). For the international validation, the AUC of the deep learning model for diagnosing the type 1 Brugada ECG pattern was 0.99 (sensitivity: 85.7%, specificity: 100.0%). CONCLUSIONS We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which is a robust screening tool with better diagnostic sensitivity than that of cardiologists. CLINICALTRIAL
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Yen-Yu Lu, Fong-Jhih Lin, Yao-Chang Chen, Yu-Hsun Kao, Satoshi Higa, Shih-Ann Chen, and Yi-Jen Chen
- International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 10993
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Pulmonary Arterial Hypertension, Monocrotaline, Endothelin-1, Organic Chemistry, Arrhythmias, Cardiac, General Medicine, Pulmonary Artery, Catalysis, Computer Science Applications, Inorganic Chemistry, Disease Models, Animal, Connexin 43, Animals, Familial Primary Pulmonary Hypertension, pulmonary arterial hypertension, atrial arrhythmogenesis, Rabbits, Physical and Theoretical Chemistry, Molecular Biology, Proto-Oncogene Proteins c-akt, and Spectroscopy
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Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.
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Yu-Hsun Kao, Shih-Yu Huang, Yao Chang Chen, Yi-Jen Chen, Shih Ann Chen, Yung-Kuo Lin, Yen-Yu Lu, and Satoshi Higa
- Journal of Cellular and Molecular Medicine
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medicine.medical_specialty, Patch-Clamp Techniques, Heart Ventricles, chemistry.chemical_element, Action Potentials, Calcium, Ventricular tachycardia, urologic and male genital diseases, Electrocardiography, right ventricular outflow tract, Internal medicine, medicine, Ventricular outflow tract, Myocyte, Animals, Humans, Myocytes, Cardiac, Patch clamp, Renal Insufficiency, Chronic, Calcium metabolism, calcium homeostasis, business.industry, Arrhythmias, Cardiac, Cell Biology, Original Articles, medicine.disease, Immunohistochemistry, Disease Models, Animal, Oxidative Stress, Sarcoplasmic Reticulum, chemistry, Heart Function Tests, Cardiology, Molecular Medicine, Original Article, ventricular tachycardia, Disease Susceptibility, Rabbits, business, chronic kidney disease, Biomarkers, Low sodium, and Kidney disease
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Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)‐induced sustained VT, and long duration of isoproterenol and tachypacing‐induced sustained and non‐sustained VT. Tachypacing‐induced sustained and non‐sustained VT in isoproterenol‐treated CKD RVOT tissues were attenuated by KB‐R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase‐positive neural density. The CKD RVOT myocytes exhibited large levels of I to, I Kr, NCX and L‐type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.
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Liu, Ching-Han, Chen, Yao-Chang, Lu, Yen-Yu, Lin, Yung-Kuo, Higa, Satoshi, Chen, Shih-Ann, and Chen, Yi-Jen
- Biomedicines; Nov2022, Vol. 10 Issue 11, p2727, 13p
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BUNDLE-branch block, VENTRICULAR tachycardia, VENTRICULAR arrhythmia, SODIUM, and INTRAVENOUS therapy
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Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia. [ABSTRACT FROM AUTHOR]
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Lu, Yen-Yu, Lin, Fong-Jhih, Chen, Yao-Chang, Kao, Yu-Hsun, Higa, Satoshi, Chen, Shih-Ann, and Chen, Yi-Jen
- International Journal of Molecular Sciences; Oct2022, Vol. 23 Issue 19, p10993, 13p
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PULMONARY arterial hypertension, ATRIAL arrhythmias, SINOATRIAL node, ENDOTHELIN receptors, PREPROENDOTHELIN, RIGHT heart atrium, CONNEXIN 43, and WESTERN immunoblotting
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Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias. [ABSTRACT FROM AUTHOR]
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Lkhagva, Baigalmaa, Lee, Ting-Wei, Lin, Yung-Kuo, Chen, Yao-Chang, Chung, Cheng-Chih, Higa, Satoshi, and Chen, Yi-Jen
- Cells (2073-4409); Sep2022, Vol. 11 Issue 18, pN.PAG-N.PAG, 22p
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HEART metabolism, DIABETES, ATRIAL fibrillation, ATRIAL arrhythmias, ENERGY metabolism, FATTY acid oxidation, and THERAPEUTICS
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Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF. [ABSTRACT FROM AUTHOR]
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LIN, YENN-JIANG, TAI, CHING-TAI, LIU, TU-YING, HIGA, SATOSHI, LEE, PI-CHANG, HUANG, JIN-LONG, YUNIADI, YOGA, HUANG, BIEN-HSIEN, LEE, KUN-TAI, LEE, SHIH-HUANG, UENG, KUANG-CHANG, HSIEH, MING-HSUNG, DING, YU-AN, and CHEN, SHIH-ANN
- Pacing and Clinical Electrophysiology. Sep 01, 2004 27(9):1231-1239
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CHANG, Shih-Lin, CHEN, Yao-Chang, HSU, Chiao-Po, KAO, Yu-Hsun, LIN, Yung-Kuo, LAI, Yu-Jun, YEH, Hung-I, HIGA, Satoshi, CHEN, Shih-Ann, and CHEN, Yi-Jen
- International journal of cardiology. 168(4):4019-4026
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Insuffisance cardiaque, oedème pulmonaire cardiogène, hypertrophie cardiaque, Heart failure, cardiogenic pulmonary edema, cardiac enlargement, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Electrodiagnostic, Electrodiagnosis, Electrodiagnóstico, Electrophysiologie, Electrophysiology, Electrofisiología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Cardiologie, Cardiology, Cardiología, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Insuffisance cardiaque, Heart failure, Insuficiencia cardíaca, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Potentiel action, Action potential, Potencial acción, Protéine choc thermique, Heat shock protein, Proteína choque térmico, Substrat, Substrate, Substrato, GGA, and Monophasic action potential
- Abstract
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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 Ca2+-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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Nobuo Shiode, Kazuyoshi Suenari, Shunsuke Tomomori, Shih Ann Chen, Takayuki Nakano, and Satoshi Higa
- Circulation Reports
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medicine.medical_specialty, Paroxysmal atrial fibrillation, business.industry, medicine.medical_treatment, Cardiac arrhythmia, Atrial fibrillation, Catheter ablation, Review, General Medicine, Cryoballoon, Ablation, medicine.disease, Balloon, Internal medicine, cardiovascular system, medicine, Cardiology, business, Stroke, and Cryoballoon ablation
- Abstract
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and induces cardiac dysfunction and stroke. The development of AF requires a trigger and also an electroanatomic substrate capable of both initiating and perpetuating AF. In the past decade, ectopic beats originating from the pulmonary veins (PV) have been identified as a source of paroxysmal AF. Thus, strategies that target the PV, including the PV antrum, are the cornerstone of most AF ablation procedures. Recently, alternative technologies to radiofrequency catheter ablation for paroxysmal AF such as balloon ablation modalities have been developed. The purpose of this review is to discuss cryoballoon ablation for paroxysmal AF.
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LIN, Yenn-Jiang, TAI, Ching-Tai, TSAI, Wen-Chin, CHANG, Chien-Jung, UENG, Kuo-Chang, HIGA, Satoshi, CHEN, Shih-Ann, KAO, Tsair, CHANG, Shih-Lin, LO, Li-Wei, TUAN, Ta-Chuan, UDYAVAR, Ameya R, WONGCHAROEN, Wanwarang, HU, Yu-Feng, and TSO, Han-Wen
- Circulation. Arrhythmia and electrophysiology. 2(3):233-241
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Genetique des eucaryotes. Evolution biologique et moleculaire, Genetics of eukaryotes. Biological and molecular evolution, Génétique classique, génétique quantitative, hybrides, Classical genetics, quantitative genetics, hybrids, Homme, Human, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Age, Edad, Analyse, Analysis, Análisis, Caractère dominant, Dominant character, Carácter dominante, Caractéristique, Characteristic, Característica, Caractéristiques, Characteristics, Características, Carte génétique, Genetic mapping, Mapa genético, Cartographie, Cartography, Cartografía, Cathéter, Catheter, Catéter, Complexe, Complexes, Complejo, Donnée, Data, Dato, Electrique, Electric, Eléctrico, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Fréquence, Frequency, Frecuencia, Homme, Human, Hombre, Intervalle, Interval, Intervalo, Isolement, Isolation, Aislamiento, Malade, Patient, Enfermo, Mécanisme, Mechanism, Mecanismo, Méthode, Method, Método, OMS, WHO, Oreillette gauche, Left atrium, Orejuela izquierda, Organisation, Organization, Organización, Résultat, Result, Resultado, Substrat, Substrate, Substrato, Système, System, Sistema, Technique, Técnica, Veine pulmonaire, Pulmonary vein, Vena pulmonar, atrial fibrillation, electrogram frequency analysis, and left atrium
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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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HU, Yu-Feng, HUANG, Jin-Long, CHANG, Chien-Jong, TSAI, Wen-Chin, LEE, Pi-Chang, TSAO, Hsuan-Ming, ISHIGAKI, Sugako, OYAKAWA, Asuka, CHEN, Shih-Ann, WU, Tsu-Juey, HIGA, Satoshi, SHIH, Chun-Ming, TAI, Ching-Tai, LIN, Yenn-Jiang, CHANG, Shih-Lin, LO, Li-Wei, and TA-CHUAN, Tuan
- The American journal of cardiology. 104(1):97-100
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Pathologie de l'appareil circulatoire, Cardiovascular disease, Aparato circulatorio patología, Trouble de l'excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble du rythme cardiaque, Arrhythmia, Arritmia, Appareil circulatoire, Circulatory system, Aparato circulatorio, Caractéristique, Characteristic, Característica, Caractéristiques, Characteristics, Características, Cardiologie, Cardiology, Cardiología, Etude comparative, Comparative study, Estudio comparativo, Sexe, Sex, Sexo, Tachycardie auriculaire, Atrial tachycardia, and Taquicardia auricular
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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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Ching-Han Liu, Yao-Chang Chen, Yen-Yu Lu, Yung-Kuo Lin, Satoshi Higa, Shih-Ann Chen, and Yi-Jen Chen
- Biomedicines, Vol 10, Iss 11, p 2727 (2022)
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Brugada syndrome, gender, lithium intoxication, sodium current dysregulation, right ventricular outflow tract, Biology (General), and QH301-705.5
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Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia.
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LIU, Tu-Ying, TAI, Ching-Tai, HUANG, Bien-Hsien, HIGA, Satoshi, LIN, Yenn-Jiang, HUANG, Jin-Long, YUNIADI, Yoga, LEE, Pi-Chang, DING, Yu-An, and CHEN, Shih-Ann
- Journal of the American College of Cardiology. 43(9):1639-1645
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Caractérisation, Characterization, Caracterización, Cardiopathie, Heart disease, Cardiopatía, Flutter auriculaire, Atrial flutter, Flutter auricular, Homme, Human, Hombre, Radiofréquence, Radiofrequency, and Radiofrecuencia
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OBJECTIVES The aim of the study was to investigate the conduction properties and anisotropy of the crista terminalis (CT) in patients with atrial flutter (AFL) using non-contact mapping. BACKGROUND The CT is a posterior barrier during typical AFL. However, the CT has transverse conduction capabilities in patients with upper loop re-entry (ULR). METHODS Twenty-two patients (16 males, 63 ± 15 years) with typical AFL and ULR were included. Non-contact mapping of the right atrium during AFL and pacing from coronary sinus (CS) and low anterolateral right atrium (LARA) was performed to evaluate transverse conduction across the CT. During ULR, the longitudinal (CVL) and transverse (CVT) conduction velocity along and across the CT were measured. The width of the CT conduction gap was evaluated to guide radiofrequency ablation (RFA). RESULTS No transverse CT gap conduction was found during typical AFL. Transverse CT gap conduction was found in three patients during CS pacing and in three patients during LARA pacing. During ULR, CVL was greater than CVT (1.28 ± 0.43 vs. 0.73 ± 0.30 m/s, p < 0.001). The CVL/CVT ratio was 1.95 ± 0.77, which was inversely related to the CT gap width (15.7 ± 6.8 mm) (p < 0.001). The RFA of the CT gap was successful in 18 patients. Four patients had recurrence of arrhythmias during the follow-up of 11 ± 3 months. CONCLUSIONS Most of the CT conduction gaps were functional and only appeared during ULR. The width of the CT gap was inversely related to the anisotropic ratio of the CT. The RFA of the CT gap was effective in eliminating ULR.
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JIN LONG HUANG, TAI, Ching-Tai, WONGCHAROEN, Wanwarang, TING, Chih-Tai, CHEN, Shih-Ann, LIN, Yenn-Jiang, HUANG, Bien-Hsien, LEE, Kun-Tai, HIGA, Satoshi, YUNIADI, Yoga, CHEN, Yi-Jen, CHANG, Shih-Lin, and LO, Li-Wei
- Journal of the American College of Cardiology. 48(3):492-498
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Appareil circulatoire, Circulatory system, Aparato circulatorio, Atypique, Atypical, Atípico, Cardiologie, Cardiology, Cardiología, Carte génétique, Genetic mapping, Mapa genético, Cartographie, Cartography, Cartografía, Conduction, Conducción, Endocarde, Endocardium, Endocardio, Flutter auriculaire, Atrial flutter, Flutter auricular, Homme, Human, Hombre, Oreillette droite, Right atrium, Orejuela derecha, Phlébologie, Phlebology, Flebología, Substrat, Substrate, and Substrato
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OBJECTIVES The purpose of this study was to investigate the relationship between the abnormal substrate and peak negative voltage (PNV) in the right atrium (RA) with atypical flutter. BACKGROUND The impact of a local abnormally low voltage electrogram on the local activation pattern and velocity of atrial flutter (AFL) remains unclear. METHODS Twelve patients with clinically documented AFL were included to undergo noncontact mapping of the RA. The atrial substrate was characterized by the: 1) activation mapping; 2) high-density voltage mapping; and 3) conduction velocity along the flutter re-entrant circuit. The normalized PNV (i.e., the relative ratio to the maximal PNV) in each virtual electrode recording was used to produce the voltage maps of the entire chamber. The protected isthmus was bordered by low voltage zones. RESULTS Atypical AFL of the RA was induced by atrial pacing in 12 patients, including 10 upper loop re-entry and 2 RA free wall re-entry flutter. These protected isthmuses were located near the crista terminalis. The mean width of the protected isthmus was 1.7 ± 0.3 cm and mean voltage at the isthmus was -0.91 ± 0.39 mV. The conduction velocities within these paths were significantly slower than outside the path (0.30 ± 0.18 m/s vs. 1.14 ± 0.41 m/s, respectively; p = 0.004). The ratiometric PNV of 37.6% of the maximal PNV had the best cut-off value to predict slow conduction, with a high sensitivity (92.3%) and specificity (85.7%). CONCLUSIONS Characterization of the RA substrate in terms of the unipolar PNV is an effective predictor of the slow conduction path within the critical isthmus of the re-entrant circuit.
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LIN, Yenn-Jiang, TAI, Ching-Tai, KAO, Tsair, TSO, Han-Wen, HIGA, Satoshi, TSAO, Hsuan-Ming, CHANG, Shih-Lin, HSIEH, Ming-Hsiung, CHEN, Shih-Ann, and MANSOUR, Moussa
- Journal of the American College of Cardiology. 47(7):1401-1409
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Analyse, Analysis, Análisis, Appareil circulatoire, Circulatory system, Aparato circulatorio, Cardiologie, Cardiology, Cardiología, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Fréquence, Frequency, Frecuencia, Phlébologie, Phlebology, Flebología, Type, and Tipo
- Abstract
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OBJECTIVES This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF). BACKGROUND A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF. METHODS Forty-four patients (age = 60 ± 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF). RESULTS In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 ± 3.3 Hz vs. 5.9 ± 1.1 Hz vs. 5.2 ± 0.85 Hz vs. 5.5 ± 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 ± 2.4 Hz vs. 5.9 ± 1.1 Hz vs. 5.9 ± 0.7 Hz vs. 5.8 ± 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035). CONCLUSIONS The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.
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LIN, Yenn-Jiang, TAI, Ching-Tai, HSIEH, Ming-Hsiung, CHEN, Shih-Ann, KAO, Tsair, TSO, Han-Wen, HUANG, Jin-Long, HIGA, Satoshi, YUNIADI, Yoga, HUANG, Bien-Hsien, LIU, Tu-Ying, and LEE, Pi-Chang
- Circulation (New York, N.Y.). 112(12):1692-1700
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Pharmacologie. Traitements medicamenteux, Pharmacology. Drug treatments, Système cardiovasculaire, Cardiovascular system, Vasodilatateurs périphériques. Vasorégulateurs cérébraux, Vasodilator agents. Cerebral vasodilators, Métabolisme général et cellulaire. Vitamines, General and cellular metabolism. Vitamins, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Vaisseaux sanguins et lymphatiques, Blood and lymphatic vessels, Maladies vasculaires des membres. Pathologie de la veine cave. Maladies vasculaires diverses, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cathéter, Catheter, Catéter, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Homme, Human, Hombre, Oreillette droite, Right atrium, Orejuela derecha, ablation, atrial fibrillation, and atrium
- Abstract
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Background-Catheter ablation of the right atrial (RA) substrate has had variable efficacy in curing paroxysmal atrial fibrillation (PAF), suggesting that RA substrate ablation can play an important role in the treatment of atrial fibrillation (AF) in some patients. The aim of this study was to investigate the electrophysiological characteristics and ablation strategy and its results in a specific group of patients with paroxysmal RA-AF. Methods and Results-The study population consisted of 13 patients (8 men; age, 64± 15 years) with drug-refractory (2± 1 drugs), frequent episodes of PAF. Provocation maneuvers did not reveal any ectopic beat-initiating AF. However, rapid atrial pacing easily induced AF. Activation mapping during sinus rhythm, atrial pacing, and AF was visualized by using a noncontact mapping system. Noncontact mapping revealed RA reentry (6 patients with single-loop circuits and 7 with double-loop circuits) with conduction through channels between lines of block, crista terminalis gaps, and the cavotricuspid isthmus, which could be identified during sinus rhythm and atrial pacing, resulting in fibrillatory conduction in other parts of the RA. The consistency of wavefront activation was confirmed by frequency analysis from equally distributed mapping sites in the RA. Short lines of ablation lesions were aimed at the conduction channels between the lines of block, crista terminalis gaps, and the cavotricuspid isthmus, resulting in bidirectional block. AF was eliminated in 11 (85%) of 13 patients, and those 11 patients with acute success were free of AF without any antiarrhythmic drugs during the long-term follow-up period (16±6 months). Conclusions-RA ablation still can cure selected patients with PAF. Linear ablation of the RA substrate guided by the electrophysiological characteristics of RA-AF is an effective approach for treating this specific group of patients with AF.
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TSAO, Hsuan-Ming, WU, Mei-Han, HIGA, Satoshi, LEE, Kun-Tai, TAI, Ching-Tai, HSU, Nai-Wei, CHANG, Cheng-Yen, and CHEN, Shih-Ann
- Chest. 128(4):2581-2587
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Anesthesia, intensive care, Anesthésie, réanimation, Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Pneumology, Pneumologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Pneumologie, Pneumology, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Anatomie, Anatomy, Anatomía, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Appareil respiratoire pathologie, Respiratory disease, Aparato respiratorio patología, Cathéter, Catheter, Catéter, Fibrillation auriculaire, Atrial fibrillation, Fibrilación auricular, Oesophage, Esophagus, Esófago, Oreillette gauche, Left atrium, Orejuela izquierda, ablation, esophagus, and left atrium
- Abstract
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Study objectives: Atrioesophageal fistulas have been reported to be a lethal complication following catheter ablation of atrial fibrillation (AF). The purpose of this study was to investigate the relationship between the esophagus and posterior left atrium (LA) and provide the anatomic information necessary to minimize the risk of esophageal injury during AF ablation. Methods and results: Forty-eight patients (43 men; mean ± SD age, 59 ± 12 years) with drug-refractory paroxysmal AF and 32 control subjects (26 men; mean age, 60 ± 9 years) were included. All underwent a CT scan for delineation of the relationship between the esophagus and posterior LA. In the paroxysmal AF group, two major types of esophageal routes were demonstrated. Type 1 routes were found in 42 patients with the lower portion of esophagus close to the ostium of the left inferior pulmonary vein (LIPV), including three subtypes of courses according to the proximity to the left superior pulmonary vein (PV) and LIPV. Type 2 routes were found in six patients with the lower portion of esophagus close to the ostium of the right inferior pulmonary vein (RIPV), including three subtypes of courses according to the proximity to the right superior PV and RIPVs. The mean shortest distance of the esophagus to the four individual PVs significantly differed between type 1 and type 2: 28.4 ± 6.1 mm vs 10.5 ± 5.7 mm (to the right superior), 19.6 ± 7.0 mm vs 3.7 ± 3.4 mm (to the right inferior), 10.1 ± 3.4 mm vs 22.8 ± 4.2 mm (to the left superior), and 2.8 ± 2.5 mm vs 18.7 ± 5.2 mm (to the left inferior), respectively (p < 0.001 for all). Contact of the esophagus and middle part of posterior LA was observed in each patient. However, direct contact of the aorta with the posterior LA wall was more frequent in type 2 than in type 1 (p = 0.001). The clinical characteristics, type of esophageal routes, distance from the esophagus to the four PVs, and diameter of the thoracic cage, LA, and aorta in the control group were similar to those in the AF group (p > 0.05 for all). Conclusion: Although the anatomic relationship between the esophagus and LA posterior wall varied widely, two major patterns of esophageal routes could be depicted. This information is important for deciding the location of the ablation lesions around the PV ostia and LA and for avoiding the potential risk of esophageal injury.
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YUNIADI, Yoga, TAI, Ching-Tai, LEE, Kun-Tai, HUANG, Bien-Hsien, LIN, Yenn-Jiang, HIGA, Satoshi, LIU, Tu-Ying, HUANG, Jin-Long, LEE, Pi-Chang, and CHEN, Shih-Ann
- Journal of the American College of Cardiology. 46(3):524-528
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Coeur, Heart, Trouble du rythme et de la conduction, Cardiac dysrhythmias, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cardiopathie, Heart disease, Cardiopatía, Electrodiagnostic, Electrodiagnosis, Electrodiagnóstico, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Algorithme, Algorithm, Algoritmo, Appareil circulatoire, Circulatory system, Aparato circulatorio, Cardiologie, Cardiology, Cardiología, Electrocardiographie, Electrocardiography, Electrocardiografía, Flutter auriculaire, Atrial flutter, Flutter auricular, Phlébologie, Phlebology, and Flebología
- Abstract
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OBJECTIVES This study was performed to differentiate upper loop re-entry (ULR) from reverse typical atrial flutter (AFL). BACKGROUND Right atrial ULR and reverse typical AFL have different mechanisms and ablation strategies, but similar electrocardiographic characteristics. METHODS This study included 26 patients with reverse typical AFL and 20 patients with ULR. The noncontact mapping system (EnSite-3000, Endocardial Solutions, St. Paul, Minnesota) was used to confirm diagnosis and guide successful radiofrequency ablation. Flutter wave polarity and amplitude in the 12-lead surface electrocardiogram were determined by two independent electrophysiologists. RESULTS The flutter wave polarity in leads I and aVL was significantly different between the reverse typical AFL and ULR groups (p £ 0.001). Voltage measurement revealed significant differences between reverse typical AFL and ULR in leads I, II, aVR, aVF, V1, and V2 (p < 0.001). A new diagnostic algorithm based on negative or isoelectric/flat flutter wave polarity and amplitude ≤0.07 mV in lead I was useful for diagnosis of ULR, with an accuracy of 90% to 97%, a sensitivity of 82% to 100%, and a specificity of 95%. CONCLUSIONS Polarity and voltage measurement of flutter wave in lead I can differentiate reverse typical AFL from ULR.
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HIGA, Satoshi, TAI, Ching-Tai, UENG, Kwo-Chang, DING, Yu-An, CHEN, Shih-Ann, LIN, Yenn-Jiang, LIU, Tu-Ying, LEE, Pi-Chang, HUANG, Jin-Long, HSIEH, Ming-Hsiung, YUNIADI, Yoga, HUANG, Bien-Hsien, and LEE, Shih-Huang
- Circulation (New York, N.Y.). 109(1):84-91
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Cardiology, blood circulation, phlebology, Cardiologie, appareil circulatoire, phlébologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Cardiologie. Appareil circulatoire, Cardiology. Vascular system, Vaisseaux sanguins et lymphatiques, Blood and lymphatic vessels, Maladies vasculaires des membres. Pathologie de la veine cave. Maladies vasculaires diverses, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Cardiopathie, Heart disease, Cardiopatía, Trouble excitabilité, Excitability disorder, Trastorno excitabilidad, Trouble rythme cardiaque, Arrhythmia, Arritmia, Ablation, Ablación, Appareil circulatoire pathologie, Cardiovascular disease, Aparato circulatorio patología, Cartographie, Cartography, Cartografía, Cathéter, Catheter, Catéter, Tachycardie auriculaire, Atrial tachycardia, and Taquicardia auricular
- Abstract
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Background-This study investigated the electrophysiologic characteristics, atrial activation pattern, and effects of radiofrequency (RF) catheter ablation guided by noncontact mapping system in patients with focal atrial tachycardia (AT). Methods and Results-In 13 patients with 14 focal ATs, noncontact mapping system was used to map and guide ablation of AT. AT origins were in the crista terminalis (n=8), right atrial (RA) free wall (n=3), Koch triangle (n=1), anterior portion of RA-inferior vena cava junction (n= 1), and superior portion of tricuspid annulus (n=1); breakout sites were in the crista terminalis (n=5), RA free wall (n=5), middle cavotricuspid isthmus (n=2), and RA-superior vena cava junction (n=2). ATs arose from the focal origins (11 ATs inside or at the border of low-voltage zone), with preferential conduction, breakout, and spread to the whole atrium. After applications of RF energy on the earliest activation site or the proximal portion of preferential conduction from AT origin, 13 ATs were eliminated without complication. During the follow-up period (8±5 months), 11 (91.7%) of the 12 patients with successful ablation were free of focal ATs. Conclusions-Focal AT originates from a small area and spreads out to the whole atrium through a preferential conduction. Application of RF energy guided by noncontact mapping system was effective and safe in eliminating focal AT.
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Jin Long Huang, Shih Ann Chen, Shih Huang Lee, Yenn Jiang Lin, Yoga Yuniadi, Pi Chang Lee, Yu An Ding, Kuang Chang Ueng, Satoshi Higa, Ming Hsung Hsieh, Bien Hsien Huang, Kun Tai Lee, Ching Tai Tai, and Tu Ying Liu
- Pacing and Clinical Electrophysiology. 27:1231-1239
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medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Atrial fibrillation, Catheter ablation, General Medicine, Propafenone, Anatomy, Reentry, Ablation, medicine.disease, medicine.anatomical_structure, Internal medicine, cardiovascular system, medicine, Cardiology, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Crista terminalis, business, Electrocardiography, Atrial flutter, and medicine.drug
- Abstract
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Paroxysmal atrial fibrillation (PAF) can be initiated by ectopic activation from the crista terminalis. The crista terminalis conduction gap is also a critical isthmus in atrial reentrant arrhythmias like upper and lower loop reentry. The aim of this study was to investigate the mechanism and results of catheter ablation for complex atrial arrhythmias originating from the crista terminalis using the noncontact mapping system (NCM). The study population consisted of six patients (5 men, 1 woman; 70 +/- 9 years) with drug refractory PAF and typical/atypical atrial flutter. NCM identified the earliest ectopic activation originating from the crista terminalis in these six patients. The reentry circuit of atypical atrial flutter propagated around the upper crista terminalis in five patients, and lower crista terminalis in one patient. The reentry circuit of atypical atrial flutter and the initial reentry circuit of AF conducted through the crista terminalis gap in all patients. Radiofrequency applications were delivered on the sites of ectopy, which initiated AF. Substrate modification was also performed over the crista terminalis gap (six patients) and cavotricuspid isthmus (three patients) responsible for the reentry. During a mean follow-up of 9 +/- 5 months (range 5-18 months), five patients were free of AF without antiarrhythmic drugs, and one patient did not have AF or atrial flutter using propafenone. NCM demonstrated the mechanism of crista terminalis ectopy-initiating AF and associated typical/atypical atrial flutter. Catheter ablation of crista terminalis ectopy and substrate for the reentry guided by NCM successfully eliminated these atrial arrhythmias.
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Yu-Feng Hu, Sugako Ishigaki, Shih Ann Chen, Ching Tai Tai, Min Hsiung Hsieh, Satoshi Higa, Li Wei Lo, Kun Tai Lee, Ta Chuan Tuan, Hsuan Ming Tsao, Yenn Jiang Lin, Shih Lin Chang, and Wanwarang Wongcharoen
- Heart rhythm. 6(5)
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Male, medicine.medical_specialty, medicine.medical_treatment, Catheter ablation, Heart Conduction System, Physiology (medical), Internal medicine, Atrial Fibrillation, Medicine, Humans, cardiovascular diseases, Heart Atria, business.industry, P wave, Body Surface Potential Mapping, Atrial fibrillation, Atrial arrhythmias, Middle Aged, medicine.disease, Ablation, Prognosis, medicine.anatomical_structure, Atrial Flutter, cardiovascular system, Cardiology, Catheter Ablation, Female, Electrical conduction system of the heart, Cardiology and Cardiovascular Medicine, business, Crista terminalis, Electrophysiologic Techniques, Cardiac, Atrial flutter, and Follow-Up Studies
- Abstract
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The regional distribution of the low-voltage zones (LVZs) may relate to the maintenance of atrial arrhythmias in the right atrium (RA).The purpose of this study was to investigate the RA substrate characteristics in different types of atrial arrhythmias originating from RA and left atrium (LA).Forty-five patients (35 men, age = 62 +/- 15 years) with RA atypical atrial flutter (n = 15, group 1), RA atrial fibrillation (AF; n = 15, no PV initiating foci, group 2), and LA AF (n = 1 5, no RA arrhythmias, group 3) referred for three-dimensional EnSite mapping were included. Voltage and activation maps were visualized.The mean voltage of the RA was lower in group 2, and compared with group 3, a voltage reduction during atrial pacing was evident in groups 1 and 2. The fixed LVZs (independent of the rhythm) were mostly located along the lower crista terminalis (CT). A functional extension of the LVZ was located on the CT in 84% of patients, sinus venosa in 18%, and free-wall region in 27%, forming the borders of the slow conduction isthmus for the reentrant circuits. The number of slow conduction isthmuses was 1.3 +/- 0.9, 2.2 +/- 1.0, and 0.87 +/- 0.74, for the groups 1-3 patients, respectively (P.05). Radiofrequency ablation connecting the LVZs successfully eliminated those isthmuses. The long-term follow-up revealed that 66% of the patients remained in sinus rhythm.Single and multiple slow conduction isthmuses bordered by the fixed and functional LVZs were critical for the reentrant circuits in the RA. The conduction isthmuses could be identified by their substrate characteristics and ablated successfully.
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Keita Tsukahara, Yasushi Oginosawa, Yoshihisa Fujino, Toshihiro Honda, Kan Kikuchi, Masatsugu Nozoe, Takayuki Uchida, Hitoshi Minamiguchi, Koichiro Sonoda, Masahiro Ogawa, Takeshi Ideguchi, Yoshihisa Kizaki, Toshihiro Nakamura, Kageyuki Oba, Satoshi Higa, Keiki Yoshida, Keishiro Yagyu, Taro Miyamoto, Yasunobu Yamagishi, Hisaharu Ohe, Ritsuko Kohno, Masaharu Kataoka, Yutaka Otsuji, and Haruhiko Abe
- Journal of Arrhythmia, Vol 37, Iss 4, Pp 1052-1060 (2021)
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anti‐tachycardia pacing therapy, implantable cardioverter defibrillator, RR interval variability, shock therapy, ventricular tachycardia, Diseases of the circulatory (Cardiovascular) system, and RC666-701
- Abstract
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Abstract Background An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability. Methods We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti‐tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated. Results Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively. Conclusions ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible.
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Li Wei Lo, Shien-Fong Lin, Shih Lin Chang, Yung Nan Tsai, Ya Wen Hsiao, Tze Fan Chao, Satoshi Higa, Yu Feng Hu, Fa Po Chung, Jo Nan Liao, Shih Ann Chen, Tsu Juey Wu, Ta Chuan Tuan, Shuen Hsin Liu, Yenn Jiang Lin, and Yu Cheng Hsieh
- Journal of molecular and cellular cardiology. 122
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0301 basic medicine, Myocardial Infarction, Gene Expression, Inflammation, Apoptosis, 030204 cardiovascular system & hematology, Pharmacology, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, In vivo, Medicine, Animals, RNA, Messenger, Ventricular remodeling, Molecular Biology, Heart Failure, Analysis of Variance, Ventricular Remodeling, business.industry, Myocardium, Interleukin-17, Interleukin, Arrhythmias, Cardiac, medicine.disease, Antibodies, Neutralizing, Fibrosis, Voltage-Sensitive Dye Imaging, CXCL1, Disease Models, Animal, 030104 developmental biology, Injections, Intravenous, Th17 Cells, Tumor necrosis factor alpha, Interleukin 17, Rabbits, medicine.symptom, Mitogen-Activated Protein Kinases, Cardiology and Cardiovascular Medicine, and business
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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 (CD4+IL-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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Tsukahara, Keita, Oginosawa, Yasushi, Fujino, Yoshihisa, Honda, Toshihiro, Kikuchi, Kan, Nozoe, Masatsugu, Uchida, Takayuki, Minamiguchi, Hitoshi, Sonoda, Koichiro, Ogawa, Masahiro, Ideguchi, Takeshi, Kizaki, Yoshihisa, Nakamura, Toshihiro, Oba, Kageyuki, Higa, Satoshi, Yoshida, Keiki, Yagyu, Keishiro, Miyamoto, Taro, Yamagishi, Yasunobu, Ohe, Hisaharu, Kohno, Ritsuko, Kataoka, Masaharu, Otsuji, Yutaka, and Abe, Haruhiko
- Journal of arrhythmia. 37(4):1052-1060
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46. Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure [2018]
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Ya Wen Hsiao, Shih Lin Chang, Satoshi Higa, Man Cai Fong, Yung Nan Tsai, Jo Nan Liao, Hsing Yuan Li, Yu Feng Hu, Tze Fan Chao, Yenn Jiang Lin, Fa Po Chung, Yao Ting Chang, Li Wei Lo, Shih Ann Chen, and Shinya Yamada
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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0301 basic medicine, Male, medicine.medical_specialty, Nitric Oxide Synthase Type III, Myocardial Infarction, Infarction, Action Potentials, Apoptosis, 030204 cardiovascular system & hematology, Arrhythmias, Kidney, Arrhythmogenic substrate, Ion Channels, atrial arrhythmogenic substrates, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Internal medicine, Atrial Fibrillation, Autonomic Denervation, Medicine, Animals, Arrhythmia and Electrophysiology, Atrial Appendage, renal denervation, Original Research, Denervation, Heart Failure, business.industry, Atrial fibrillation, Atrial Remodeling, medicine.disease, Fibrosis, Disease Models, Animal, 030104 developmental biology, PI3K/AKT/eNOS signaling, Heart failure, Cardiology, cardiovascular system, Atrial Function, Left, Rabbits, Phosphatidylinositol 3-Kinase, Cardiology and Cardiovascular Medicine, business, Proto-Oncogene Proteins c-akt, and Signal Transduction
- Abstract
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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, Kv LQT 1, 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%, P 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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Akira Maesato, Satoshi Higa, Ichiro Chinen, Sugako Ishigaki, Yenn-Jiang Lin, Machiko Yajima, Kazuhito Tatsu, Kotaro Obunai, Yoichi Uechi, Moriichi Sugama, Hiroaki Masuzaki, and Shih-Ann Chen
- Journal of Arrhythmia. 2011 27(suppl):377-377
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Yenn-Jiang, Lin, Ching-Tai, Tai, Tu-Ying, Liu, Satoshi, Higa, Pi-Chang, Lee, Jin-Long, Huang, Yoga, Yuniadi, Bien-Hsien, Huang, Kun-Tai, Lee, Shih-Huang, Lee, Kuang-Chang, Ueng, Ming-Hsung, Hsieh, Yu-An, Ding, and Shih-Ann, Chen
- Pacing and clinical electrophysiology : PACE. 27(9)
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Male, Electrocardiography, Atrial Flutter, Atrial Fibrillation, Body Surface Potential Mapping, Catheter Ablation, Humans, Female, Middle Aged, Electrophysiologic Techniques, Cardiac, Aged, and Follow-Up Studies
- Abstract
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Paroxysmal atrial fibrillation (PAF) can be initiated by ectopic activation from the crista terminalis. The crista terminalis conduction gap is also a critical isthmus in atrial reentrant arrhythmias like upper and lower loop reentry. The aim of this study was to investigate the mechanism and results of catheter ablation for complex atrial arrhythmias originating from the crista terminalis using the noncontact mapping system (NCM). The study population consisted of six patients (5 men, 1 woman; 70 +/- 9 years) with drug refractory PAF and typical/atypical atrial flutter. NCM identified the earliest ectopic activation originating from the crista terminalis in these six patients. The reentry circuit of atypical atrial flutter propagated around the upper crista terminalis in five patients, and lower crista terminalis in one patient. The reentry circuit of atypical atrial flutter and the initial reentry circuit of AF conducted through the crista terminalis gap in all patients. Radiofrequency applications were delivered on the sites of ectopy, which initiated AF. Substrate modification was also performed over the crista terminalis gap (six patients) and cavotricuspid isthmus (three patients) responsible for the reentry. During a mean follow-up of 9 +/- 5 months (range 5-18 months), five patients were free of AF without antiarrhythmic drugs, and one patient did not have AF or atrial flutter using propafenone. NCM demonstrated the mechanism of crista terminalis ectopy-initiating AF and associated typical/atypical atrial flutter. Catheter ablation of crista terminalis ectopy and substrate for the reentry guided by NCM successfully eliminated these atrial arrhythmias.
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Akira Maesato, Satoshi Higa, Ichiro Chinen, Sugako Ishigaki, Yenn-Jiang Lin, Machiko Yajima, Kazuhito Tatsu, Kotaro Obunai, Yoichi Uechi, Moriichi Sugama, Hiroaki Masuzaki, and Shih-Ann Chen
- Journal of Arrhythmia. 2011 27(suppl):377-377
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Baigalmaa Lkhagva, Ting-Wei Lee, Yung-Kuo Lin, Yao-Chang Chen, Cheng-Chih Chung, Satoshi Higa, and Yi-Jen Chen
- Cells, Vol 11, Iss 2915, p 2915 (2022)
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atrial arrhythmogenesis, mitochondria, energy metabolism, glucose oxidation, fatty acid oxidation, ketone body, Cytology, and QH573-671
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Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF.
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