Shih-Ann Chen

National Yang Ming University, T’ai-pei, Taipei, Taiwan

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Publications (449)1714.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is associated with cognitive decline and may contribute to an increased risk of dementia. The goal of the present study was to investigate whether statin use prevented non-vascular dementia in subjects with AF. Data from the National Health Insurance Research Database of Taiwan were used in this study. The study group comprised 51,253 AF subjects aged ≥60years who had received statin treatment. For each study patient, four age- and sex-matched AF subjects without statin exposure were selected as the control group (n=205,012). The risk of non-vascular dementia was compared between the statin and control groups. During the follow-up period, 17,201 patients experienced non-vascular dementia. The annual incidence of non-vascular dementia was lower in the statin group than in the control group (1.89% vs. 2.20%; p<0.001). Statin use exhibited a protective effect on the occurrence of non-vascular dementia, with an adjusted hazard ratio (HR) of 0.832 (95% confidence interval=0.801-0.864). Among statin types, the use of rosuvastatin was associated with the largest risk reduction (adjusted HR=0.661). Statin exposure duration was related inversely to the risk of non-vascular dementia. In this large-scale nationwide cohort study, statin use was associated with a lower risk of non-vascular dementia in AF. Use of more potent statin and longer exposure time may be associated with greater benefits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 10/2015; 196. DOI:10.1016/j.ijcard.2015.05.159 · 6.18 Impact Factor
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    ABSTRACT: Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. This study compared electrophysiological characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein isolation (PVI) in paroxysmal AF and additional substrate modification in non-paroxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3±0.4 vs. 1.0±0.2, P<0.01) and higher prevalence of non-PV foci (42% vs. 23%, P<0.01). Ectopic foci from ligament of Marshall (LOM) were demonstrated more often in hyperthyroid patients (7.1% vs. 1.6%, P<0.01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio=2.07, 95% confidence interval=1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and without hyperthyroid history. Patients with hyperthyroid history had significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci comparing to euthyroid patients which resulted in the higher AF recurrence rate after single procedure. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 06/2015; DOI:10.1016/j.hrthm.2015.06.004 · 4.92 Impact Factor
  • Tze-Fan Chao, Li-Wei Lo, Shih-Ann Chen
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    ABSTRACT: Although the CHA2DS2-VASc score is recommended by both American and European guidelines for stroke risk stratification in atrial fibrillation (AF), the treatment recommendations for a CHA2DS2-VASc score of 1 are less clear. The authors used the “Taiwan National Health Insurance Research Database” to investigate the risk of ischemic stroke in patients with a single additional stroke risk factor (ie. CHA2DS2-VASc score = 1 (males) or 2 (females)). Among 12935 male AF patients with a CHA2DS2-VASc score of 1, 1858 patients (14.4%) experienced ischemic stroke with an annual stroke rate of 2.75%. The risk of ischemic stroke ranged from 1.96%/year for AF patients with vascular disease to 3.50%/year for those aged 65-74 years. For AF females with a CHA2DS2-VASc score of 2, 14.9% of them experienced ischemic stroke with an annual stroke rate of 2.55%. The risk of ischemic stroke increased from 1.91%/year for patients with hypertension to 3.34%/year for those aged 65-74 years.This article is protected by copyright. All rights reserved
    Journal of Cardiovascular Electrophysiology 06/2015; 26(6):703-704. DOI:10.1111/jce.12679 · 2.88 Impact Factor
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    ABSTRACT: Orthostatic hypotension (OH) is a common condition encountered in the elderly. The present study aimed to examine the relationship between OH and adverse events in Asians. We used the "National Health Insurance Research Database" in Taiwan. A total of 1226 patients with OH and without previous history of ischemic stroke and myocardial infarction were identified as the study group. For each study patient, ten age-, sex- and comorbidity-matched subjects without OH were selected to constitute the control group (n=12,260). The clinical endpoints were ischemic stroke, myocardial infarction and all-cause mortality. The mean age of the study population was 54.8±19.0years and males accounted for 47% of the patients. During the follow-up of 4.5±2.9years, 704 (5.2%) patients developed ischemic stroke, 190 (1.4%) patients developed myocardial infarction, and 733 (5.4%) patients died. In the multivariable Cox regression analyses which were adjusted for age, gender and differences in medication usages, OH was significantly associated with an increased risk of ischemic stroke (hazard ratio [HR]=1.40, 95% confidence interval (CI)=1.09-1.81, p=0.009), all-cause mortality (HR=1.35; 95% CI=1.05-1.73, p=0.018) and adverse events (ischemic stroke, myocardial infarction or mortality) (HR=1.41; 95% CI=1.18-1.68, p<0.001). OH is an independent factor associated with ischemic stroke and mortality in Asians. Whether aggressive managements for stroke prevention could improve the outcome for OH patients deserves further study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 05/2015; 195. DOI:10.1016/j.ijcard.2015.05.060 · 6.18 Impact Factor
  • Tze-Fan Chao, Chia-Jen Liu, Shih-Ann Chen
    Journal of the American College of Cardiology 04/2015; 65(15):1603-4. DOI:10.1016/j.jacc.2014.12.065 · 15.34 Impact Factor
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    ABSTRACT: Ventricular arrhythmia (VA) can occur during propafenone therapy in atrial fibrillation (AF) patients with structurally normal heart. This study was designed to evaluate the incidence and characteristics of propafenone associated VAs in AF patients with structurally normal heart. First, we studied and compared the risk of new-onset VAs between AF patients with structurally normal heart taking and not taking propafenone in a nationwide longitudinal cohort in Taiwan (n = 127197, since 2000). Then, we investigated the association between propafenone and VA in AF patients with structurally normal heart in a single-center database (n = 396). In the nationwide cohort, 102 patients (0.008% per patient-year) developed ventricular tachycardia (VT)/ ventricular fibrillation (VF) during a follow-up period of 9.8 ± 3.5 years. After multivariate Cox regression analysis, propafenone treatment was a significant risk factor for new-onset VT/VF with a hazard ratio (HR) of 3.59 (95% confidence interval (CI)= 1.30-9.89, p value = 0.0136). Propafenone treatment offered protection against ischemic stroke with HR 0.649 (95% CI =0.55-0.77, p value <0.001).In the single center study using ECG and medical records, presence of inferior J wave, wider QRS, and old age were independent risk factors for VA after adjustment of clinical, biochemical and echocardiographic variables. Albeit low incidence, propafenone therapy for AF was associated new-onset VA in the nationwide longitudinal cohort study in Taiwan. Old age, presence of inferior lead J wave, and wider QRS in ECG were significant risk factors in our single center study. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 04/2015; 12(7). DOI:10.1016/j.hrthm.2015.04.018 · 4.92 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0123116. DOI:10.1371/journal.pone.0123116 · 3.53 Impact Factor
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    ABSTRACT: Sex hormones and calcium (Ca(2+)) 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 Ca(2+) homeostasis. Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10months) before and after caffeine (1mM), isoproterenol (1μM), adenosine (10μM) and flecainide (5μM) administration. The Fluo-3 fluorescence Ca(2+) imaging with confocal microscopy and western blots were used to investigate intracellular Ca(2+) (Ca(2+)i) transients, Ca(2+) sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. We found that ARKO RVOTs (n=13) had longer AP duration, faster burst firing (5.4±0.7 vs. 3.4±0.7Hz, 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±0.4spark/mm/s, P<0.05) and incidence (89% vs. 47%, P<0.05) of Ca(2+) sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO and WT RVOT myocytes exhibit similar Ca(2+)i transients and SR Ca(2+) content, and less expression of calsequestrin. ARKO changes RVOT electrophysiology and Ca(2+) homeostasis with increased ventricular arrhythmogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 04/2015; 189:172-181. DOI:10.1016/j.ijcard.2015.04.080 · 6.18 Impact Factor
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    ABSTRACT: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited genetic disease caused by defective desmosomal proteins, and it has typical histopathological features characterized by predominantly progressive fibro-fatty infiltration of the right ventricle. Clinical presentations of ARVD/C vary from syncope, progressive heart failure (HF), ventricular tachyarrhythmias, and sudden cardiac death (SCD). The 2010 modified Task Force criteria were established to facilitate the recognition and diagnosis of ARVD/C. An implantable cardiac defibrillator (ICD) remains to be the cornerstone in prevention of SCD in patients fulfilling the diagnosis of definite ARVD/C, especially among ARVD/C patients with syncope, hemodynamically unstable ventricular tachycardia (VT), ventricular fibrillation, and aborted SCD. Further risk stratification is clinically valuable in the management of patients with borderline or possible ARVD/C and mutation carriers of family members. However, given the entity of heterogeneous penetrance and non-uniform phenotypes, the standardization of clinical practice guidelines for at-risk individuals will be the next frontier to breakthrough.
    Journal of Cardiology 03/2015; 65(6). DOI:10.1016/j.jjcc.2014.12.023 · 2.57 Impact Factor
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    ABSTRACT: 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. 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. Celecoxib (0.3, 1, and 3μM) 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 10μM) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3μM) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10μM) suppressed celecoxib (3μM)-induced PV burst firings in 6 (86%, p<0.05) of 7 PVs. KB-R7943 (10μM) suppressed celecoxib (3μM)-induced PV burst firings in 5 (71%, p<0.05) of 7 PVs. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 03/2015; 184:559-567. DOI:10.1016/j.ijcard.2015.03.066 · 6.18 Impact Factor
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    ABSTRACT: Although the CHA2DS2-VASc (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female) score is recommended by both American and European guidelines for stroke risk stratification in atrial fibrillation (AF), the treatment recommendations for a CHA2DS2-VASc score of 1 are less clear. This study aimed to investigate the risk of ischemic stroke in patients with a single additional stroke risk factor (i.e., CHA2DS2-VASc score = 1 [males] or 2 [females]) and the impact of different component risk factors. We used the National Health Insurance Research Database in Taiwan. Among 186,570 AF patients not on antiplatelet or anticoagulant therapy, we evaluated males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2. The clinical endpoint was the occurrence of ischemic stroke. Among 12,935 male AF patients with a CHA2DS2-VASc score of 1, 1,858 patients (14.4%) experienced ischemic stroke during follow-up (5.2 ± 4.3 years), with an annual stroke rate of 2.75%. Ischemic stroke risk ranged from 1.96%/year for men with vascular disease to 3.50%/year for those 65 to 74 years of age. For 7,900 females with AF and a CHA2DS2-VASc score of 2, 14.9% experienced ischemic stroke for an annual stroke rate of 2.55%. Ischemic stroke risk increased from 1.91%/year for women with hypertension to 3.34%/year for those 65 to 74 years of age. Not all risk factors in CHA2DS2-VASc score carry an equal risk, with age 65 to 74 years associated with the highest stroke rate. Oral anticoagulation should be considered for AF patients with 1 additional stroke risk factor given their high risk of ischemic stroke. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 02/2015; 65(7):635-642. DOI:10.1016/j.jacc.2014.11.046 · 15.34 Impact Factor
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    ABSTRACT: Ablations of atrial fibrillation (AF) have become more widely performed, and the strategy about long-term usage of oral anticoagulants (OACs) after catheter ablation is an important issue, especially for patients without obvious evidences of recurrences. The annual rate of thromboembolic (TE) event after catheter ablation was less than 1%. CHADS2 and CHA2DS2-VASc scores could be used to identify patients at the risk of TE events after ablations who should continue OACs regardless of the status of recurrence. Despite the improvement in understanding of AF and advancement of technology in catheter ablation, the long-term successful rates of paroxysmal and non-paroxysmal AF are around 50% and 30%, respectively. Patients with a high CHADS2 score are at a high risk of recurrence which could continuously occur after the catheter ablation without reaching a plateau. Among the patients with a CHADS2 score of ≥3, 26.9% of the recurrences happened 2 years post catheter ablation. Compared to the episodes of AF before catheter ablation, the AF episodes after ablation procedures are less symptomatic and shorter in duration. Therefore, it may not be safe to stop OACs for patients with a high risk score since the AF episodes are difficult to be detected after ablation procedures, but remain dangerous. In conclusion, the decision about the long-term strategy of OACs should be based on patients' baseline clinical risk scores, such as CHADS2 and CHA2DS2-VASc scores, rather than the status of recurrence.
    02/2015; 7(2):172-7. DOI:10.3978/j.issn.2072-1439.2015.01.18
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    ABSTRACT: Resveratrol has shown benefits in reducing ventricular remodeling and arrhythmias. This study aimed to assess the therapeutic efficacy of resveratrol in reducing atrial fibrillation (AF) in a heart failure (HF) model and explore underlying mechanisms. HF rabbits were created 4 weeks after undergoing coronary ligation. Group 1 (n = 6) included (a) normal; (b) HF sham; (c) HF rabbits treated for 1 week with intraperitoneal injections of resveratrol; (d) resveratrol + wortmannin, and (e) resveratrol + diphenyleneiodonium chloride (DPI). All rabbits underwent epicardial catheter stimulation. Collagen content, mRNA and protein expression in ionic channels, and PI3K/AKT/eNOS signaling pathways were studied in left atrial appendage (LAA) preparations. To investigate acute drug effects on left atrial (LA) electrophysiology, Groups 2 a-e (n = 6) were subjected to Langendorff perfusion. Higher AF inducibility was found in the HF group and groups that were administered PI3K and eNOS inhibitors than in the normal and resveratrol-treated groups (P < 0.001). Histological analysis of LAA revealed a decrease in fibrosis in resveratrol-treated groups compared with the HF group (8.95% ± 1.53% vs. 26.62% ± 2.19%, P < 0.001). In real-time PCR analysis, ionic channels including Kv1.4, Kv1.5, KvLQT1, Kir2.1, Nav1.5, Cav1.2, NCX, SERCA2a, and PLB were upregulated by resveratrol. PI3K, AKT, and eNOS mRNA and protein expressions were upregulated by resveratrol but were inhibited by the co-administration of wortmannin and DPI. Resveratrol decreases LA fibrosis and regulates variation in ionic channels to reduce AF through the PI3K/AKT/eNOS signaling pathway. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2015; 12(5). DOI:10.1016/j.hrthm.2015.01.044 · 4.92 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is the most common cardiac arrhythmia. However, the development of preventative therapies for AF has been disappointing. The infiltration of immune cells and proteins that mediate the inflammatory response in cardiac tissue and circulatory processes is associated with AF. Furthermore, the presence of inflammation in the heart or systemic circulation can predict the onset of AF and recurrence in the general population, as well as in patients after cardiac surgery, cardioversion, and catheter ablation. Mediators of the inflammatory response can alter atrial electrophysiology and structural substrates, thereby leading to increased vulnerability to AF. Inflammation also modulates calcium homeostasis and connexins, which are associated with triggers of AF and heterogeneous atrial conduction. Myolysis, cardiomyocyte apoptosis, and the activation of fibrotic pathways via fibroblasts, transforming growth factor-β and matrix metalloproteases are also mediated by inflammatory pathways, which can all contribute to structural remodelling of the atria. The development of thromboembolism, a detrimental complication of AF, is also associated with inflammatory activity. Understanding the complex pathophysiological processes and dynamic changes of AF-associated inflammation might help to identify specific anti-inflammatory strategies for the prevention of AF.
    Nature Reviews Cardiology 01/2015; 12(4). DOI:10.1038/nrcardio.2015.2 · 10.15 Impact Factor
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    ABSTRACT: Noncompliant patients might be at risk of thromboembolism because of the short half-life and rapid offset of dabigatran etexilate. The assessment and management of dabigatran noncompliance should be optimized. A total of 150 nonvalvular atrial fibrillation patients receiving dabigatran were prospectively enrolled and followed for drug compliance and persistence. Noncompliance was identified by questionnaires and interviews. The hemoclot thrombin inhibitor (HTI) assay was used for monitoring the plasma dabigatran levels. Sixteen patients were noncompliant (10.7%). None of the clinical characteristics were significantly relevant to noncompliance after multivariate analysis. The dabigatran plasma level based on HTI was the only independent predictor of noncompliance (odds ratio: 0.97 per ng/mL, P = 0.003). The prothrombin time (PT), international normalized ratio of PT (INR [PT]), and activated partial thromboplastin time did not differ between compliant and noncompliant patients. During the follow-up, the persistent prescription of dabigatran was noted in 75% of noncompliant patients without improvement in compliance. The drug discontinuation rate was higher in the noncompliant than compliant patients (6.7% vs. 25%, P = 0.035). None of the patients in either group received warfarin after discontinuing dabigatran. The assessment and management of dabigatran noncompliance is generally ignored in clinical practice. The measurement of dabigatran plasma levels by HTI could be a reliable and simple method to identify noncompliant patients. ©2015 Wiley Periodicals, Inc.
    Pacing and Clinical Electrophysiology 01/2015; 38(4). DOI:10.1111/pace.12575 · 1.25 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients and negatively impacts patient outcomes. We explored the incidence and risk factors for new-onset AF among patients with ESRD undergoing renal replacement therapy, without a prior history of AF, retrieved from Taiwan's National Health Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one age- and gender-matched control and one similarly matched patient with chronic kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD. The study endpoint was the occurrence of new-onset AF and patients were followed an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per 1000 person-years for ESRD, CKD, and control patients, respectively. Among patients with ESRD, age, hypertension, heart failure, coronary artery disease, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease were significant risk factors for new-onset AF. Thus, patients with ESRD had a significantly higher risk of new-onset AF. The presence of multiple risk factors was associated with a higher possibility of AF occurrence.Kidney International advance online publication, 14 January 2015; doi:10.1038/ki.2014.393.
    Kidney International 01/2015; 87(6). DOI:10.1038/ki.2014.393 · 8.52 Impact Factor
  • 01/2015; 1(1):18-21. DOI:10.1016/j.hrcr.2014.10.003
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    ABSTRACT: Multiform premature ventricular complexes (PVCs) are common electrocardiographic abnormalities in patients with structurally normal hearts. However, the prognostic value of these complexes remains unclear. This study aimed to clarify the role of PVC polymorphism in predicting adverse outcomes. We examined the database for 24-hour electrocardiography monitoring between January 1, 2002 and December 31, 2004. We analyzed 3351 individuals with apparently normal hearts. Kaplan-Meier curves and multivariate Cox proportional hazards models were employed to estimate the effect of multiform PVC and uniform PVC on the number of incident adverse events. Average follow-up time was 10±1years. Patients with multiform PVC were older and had a higher prevalence of comorbidities. In multivariate analysis, patients with multiform PVC had an increased incidence of mortality (hazard ratio [HR]: 1.642, 95% confidence interval [CI]: 1.327-2.031), hospitalization (HR: 1.196, 95% CI: 1.059-1.350), cardiovascular hospitalization (HR: 1.289, 95% CI: 1.030-1.613), new-onset heart failure (HF; HR: 1.456, 95% CI: 1.062-1.997), transient ischemic accident (HR: 1.411, 95% CI 1.063-1.873), and new-onset atrial fibrillation (AF; HR: 1.546, 95% CI: 1.058-2.258) compared to the group without PVC. Patients with multiform PVC had a higher rate of mortality (HR: 1.231, 95% CI: 1.033-1.468) and all cause-hospitalization (HR: 1.147, 95% CI: 1.025-1.283) compared with patients with uniform PVC. The presence of multiform PVC was associated with a higher incidence of mortality, hospitalization, transient ischemic attack, new-onset AF, and new-onset HF independent of other clinical risk factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 11/2014; 180C:80-85. DOI:10.1016/j.ijcard.2014.11.110 · 6.18 Impact Factor
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    ABSTRACT: A new scoring system, the anticoagulation and risk factors in atrial fibrillation (ATRIA) score, was proposed for risk stratification in patients with atrial fibrillation (AF). Whether the ATRIA scheme can adequately identify patients who are at low risk of ischemic stroke remains unknown.
    Journal of the American College of Cardiology 10/2014; 64(16):1658-65. DOI:10.1016/j.jacc.2014.06.1203 · 15.34 Impact Factor
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    ABSTRACT: Pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation (AF). Histone deacetylases (HDACs) are vital to calcium homeostasis and AF genesis. However, the electrophysiological effects of HDAC inhibition were unclear. This study evaluated whether HDAC inhibition can regulate PV electrical activity through calcium modulation. Whole-cell patch-clamp, confocal microscopic with fluorescence, and Western blot were used to evaluate electrophysiological characteristics and Ca(2+) dynamics in isolated rabbit PV cardiomyocytes with and without MPT0E014 (a pan HDAC inhibitor), MS-275 (HDAC1 and 3 inhibitor), and MC-1568 (HDAC4 and 6 inhibitor) for 5~8h. Atrial electrical activity and induced-AF (rapid atrial pacing and acetylcholine infusion) were measured in rabbits with and without MPT0E014 (10mg/kg treated for 5hours) in vivo. MPT0E014 (1μM)-treated PV cardiomyocytes (n=12) had slower beating rates (2.1±0.2 vs. 2.8±0.1Hz, p<0.05) than control PV cardiomyocytes. However, control (n=11) and MPT0E014 (1μM)-treated (n=12) SAN cardiomyocytes had similar beating rates (3.2±0.2 vs. 2.9±0.3Hz). MS-275-treated PV cardiomyocytes (n=12, 2.3±0.2Hz), but not MC-1568-treated PV cardiomyocytes (n=14, 3.1±0.3Hz) had slower beating rates than control PV cardiomocytes. MPT0E014-treated PV cardiomyocytes (n=14) had a lower frequency (2.4±0.6 vs. 0.3±0.1 spark/mm/s, p<0.05) of Ca(2+) sparks than control PV (n=17) cardiomyocytes. As compared to control, MPT0E014-treated PV cardiomyocytes had reduced Ca(2+) transient amplitudes, sodium-calcium exchanger currents, and ryanodine receptor expressions. Moreover, MPT0E014-treated rabbits had less AF and shorter AF duration than control rabbits. In conclusions, HDAC inhibition reduced PV arrhythmogenesis and AF inducibility with modulation on calcium homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 10/2014; 177(3):982-989. DOI:10.1016/j.ijcard.2014.09.175 · 6.18 Impact Factor

Publication Stats

8k Citations
1,714.74 Total Impact Points

Institutions

  • 1993–2015
    • National Yang Ming University
      • School of Medicine
      T’ai-pei, Taipei, Taiwan
  • 1992–2015
    • Taipei Veterans General Hospital
      • Cardiology Division
      T’ai-pei, Taipei, Taiwan
  • 2012
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2011
    • Buddhist Tzu Chi General Hospital
      T’ai-pei, Taipei, Taiwan
    • National Defense Medical Center
      T’ai-pei, Taipei, Taiwan
  • 2009
    • University of the Ryukyus
      • Faculty of Medicine
      Okinawa, Okinawa, Japan
    • Chiang Mai University
      • Department of Internal Medicine
      Chiang Mai, Chiang Mai Province, Thailand
  • 2003–2008
    • Chung Shan Medical University
      • Institute of Medicine
      Taichung, Taiwan, Taiwan
  • 2000–2008
    • Shin Kong Wu Ho-Su Memorial Hospital
      T’ai-pei, Taipei, Taiwan
  • 2007
    • Taipei Medical University
      • Division of Cardiovascular Medicine
      T’ai-pei, Taipei, Taiwan
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
  • 2004–2005
    • Fu Jen Catholic University
      • School of Medicine
      T’ai-pei, Taipei, Taiwan
    • Kuang Tien General Hospital
      臺中市, Taiwan, Taiwan
    • Mackay Memorial Hospital
      • Department of Internal Medicine
      T’ai-pei, Taipei, Taiwan
  • 2002–2003
    • Wan Fang Hospital
      T’ai-pei, Taipei, Taiwan