Browsing by Author "Chen, Shih-Ann"

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A Novel and Simple Algorithm Using Surface Electrocardiogram That Localizes Accessory Conduction Pathway in Wolff-Parkinson-White Syndrome in Pediatric Patients
(2019-09-01)
Li, Hsing-Yuan
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Chang, Shih-Lin
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Chuang, Chi-Hsi
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Lin, Ming-Chih
;
Lin, Yenn-Jiang
Background: The location of the accessory pathway (AP) can be precisely identified on surface electrocardiography (ECG) in adults with Wolff-Parkinson-White (WPW) syndrome. However, current algorithms to locate the AP in pediatric patients with WPW syndrome are limited. Objective: To propose an optimal algorithm that localizes the AP in pediatric patients with WPW syndrome. Methods: From 1992 to 2016, 180 consecutive patients aged below 18 years with symptomatic WPW syndrome were included. After the exclusion of patients with non-descriptive electrocardiography (ECG), multiple APs, congenital heart diseases, non-inducible tachycardia, and those who received a second ablation, 104 patients were analyzed retrospectively. Surface ECG was obtained before ablation and evaluated by using previously documented algorithms, from which a new pediatric algorithm was developed. Results: Previous algorithms were not highly accurate when used in pediatric patients with WPW syndrome. In the new algorithm, the R/S ratio of V1 and the polarity of the delta wave in lead I could distinguish right from the left side AP with 100% accuracy. The polarity of the delta wave of lead V1 could distinguish free wall AP from septal AP with an accuracy of 100% in left-side AP, compared to 88.6% in leads III and V1 for right-side AP. The overall accuracy was 92.3%. Conclusions: This simple, novel algorithm could differentiate left from right AP and septal from free wall AP in pediatric patients with WPW syndrome.
Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia
(2015-06-15)
Tsai, Wen-Chin
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Lu, Yen-Yu
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Chen, Yao-Chang
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Chang, Chien-Jung
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Kao, Yu-Hsun
Background: Sex hormones and calcium (Ca2+) regulation play roles in the pathophysiology of ventricular tachycardia from right ventricular outflow tract (RVOT). The purpose of this study was to evaluate whether androgen receptor knockout (ARKO) can increase RVOT arrhythmogenesis through modulating RVOT electrophysiology and Ca2+ homeostasis. Methods: Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10 months) before and after caffeine (1 mM), isoproterenol (1 mu M), adenosine (10 mu M) and flecainide (5 mu M) administration. The Fluo-3 fluorescence Ca2+ imaging with confocal microscopy and western blots were used to investigate intracellular Ca2+ (Ca-i(2+)) transients, Ca2+ sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. Results: We found that ARKO RVOTs (n = 13) had longer AP duration, faster burst firing (5.4 +/- 0.7 vs. 3.4 +/- 0.7 Hz, P < 0.05), and higher incidence of early afterdepolarizations (82% vs. 8%, P < 0.001) than WT RVOTs (n = 11). Adenosine and flecainide can suppress caffeine-or isoproterenol-induced spontaneous rates and burst firing in WT RVOTs, but not in ARKO RVOTs. ARKO RVOT myocytes had a higher frequency (7.7 +/- 2.8 vs. 1.3 +/- 0.4 spark/mm/s, P < 0.05) and incidence (89% vs. 47%, P < 0.05) of Ca2+ sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO andWT RVOT myocytes exhibit similar Ca-i(2+) transients and SR Ca2+ content, and less expression of calsequestrin. Conclusions: ARKO changes RVOT electrophysiology and Ca2+ homeostasis with increased ventricular arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Effects of long-term exercise on arrhythmogenesis in aged hypertensive rats
(2018-11-01)
Sung, Yen-Ling
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Wu, Chih-En
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Syu, Jhen-Yang
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Kuo, Terry B. J.
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Li, Jai-Yi
Chronic hypertension is a multifactorial disease that is highly associated with cardiovascular disorders. Physical activity, such as long-term exercise, is advocated as a treatment for hypertension, but the responses of different age groups to long-term exercise are unknown. We used aged spontaneous hypertensive rats (SHRs, 80 weeks old) to test the hypothesis that long-term exercise compensated for deficient autonomic control and reduced susceptibility to ventricular tachycardia (VT) and ventricular fibrillation (VF) in this animal model. The aged SHRs were divided into control and voluntary exercise groups. Ambulatory electrocardiography was recorded for the heart rate variability (HRV) analysis. Programmed stimulation was applied to exposed hearts to induce ventricular arrhythmia in situ. Then, the hearts were isolated for an optical mapping study. The results showed that increased HRV indices were broadly related to vagal dominance in the high-intensity exercise group. Exercise altered the electrical propagation dynamic properties, such as the action potential duration restitution (APDR). Furthermore, the VF inducibility decreased with increased exercise intensity. Taken together, our results suggest that long-term exercise reduces the risk of arrhythmogenesis in aged SHRs through enhanced vagal control and stabilized electrical dynamics.
Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure
(2018-09-01)
Chang, Shih-Lin
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Hsiao, Ya-Wen
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Tsai, Yung-Nan
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Lin, Shien-Fong
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Liu, Shuen-Hsin
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.
Large-scale Classification of 12-lead ECG with Deep Learning
(2019-01-01)
Chen, Yu-Jhen
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Liu, Chien-Liang
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Tseng, Vincent S.
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Hu, Yu-Feng
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Chen, Shih-Ann
The 12-lead Electrocardiography(ECG) is the gold standard in diagnosing cardiovascular diseases, but most previous studies focused on 1-lead or 2-lead ECG. This work uses a large data set, comprising 7,704 12-lead ECG samples, as the data source, and the goal is to develop a classification model for six common types of urgent arrhythmias. We consider the characteristics of multivariate time-series data to design a novel deep learning model, combining convolutional neural network (CNN) and long short-term memory (LSTM) to learn feature representations as well as the temporal relationship between the latent features. The experimental results indicate that the proposed model achieves promising results and outperforms the other alternatives. We also provide brief analysis about the proposed model.
Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia
(2016-12-14)
Weng, Ching-Hui
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Chung, Fa-Po
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Chen, Yao-Chang
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Lin, Shien-Fong
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Huang, Po-Hsun
Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage.
Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis
(2015-04-01)
Chang, Chien-Jung
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Cheng, Chen-Chuan
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Yang, Ten-Fang
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Chen, Yao-Chang
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Lin, Yung-Kuo
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. Methods: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. Results: Celecoxib (0.3, 1, and 3 mu M) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p < 0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 mu M) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 mu M) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 mu M) suppressed celecoxib (3 mu M)-induced PV burst firings in 6 (86%, p < 0.05) of 7 PVs. KB-R7943 (10 mu M) suppressed celecoxib (3 mu M)-induced PV burst firings in 5 (71%, p < 0.05) of 7 PVs. Conclusions: Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium
(2014-01-01)
Chang, Chien-Jung
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Yang, Ten-Fang
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Lee, Tin-I
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Chen, Yao-Chang
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Kao, Yu-Hsun
Background:The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. Methods: Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. Results: WKY (n = 5), SHR (n =7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptintreated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptintreated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. Conclusions: Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension.
Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia
(2020-02-21)
Hsieh, Yu-Cheng
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Hsieh, Wan-Hsin
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Li, Cheng-Hung
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Liao, Ying-Chieh
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Lin, Jiunn-Cherng
Introduction High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. Method and results Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30 degrees C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13 +/- 0.10 at TH to 0.09 +/- 0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59 +/- 0.73 at TH to 0.30 +/- 0.49 (p = 0.036). VF inducibility decreased, from 48 +/- 31% at TH to 22 +/- 32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). Conclusion Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH.