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INTRODUCTION: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes. METHODS AND ANALYSIS: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results. ETHICS AND DISSEMINATION: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000047023.

DOI： 10.1136/bmjopen-2022-068894

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BACKGROUND: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. METHODS: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. FINDINGS: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. INTERPRETATION: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. FUNDING: None.

DOI： 10.1016/j.ebiom.2022.104388

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Long QT syndrome (LQTS) is one of the most common inherited arrhythmias and multiple genes have been reported as causative. Presently, genetic diagnosis for LQTS patients is becoming widespread and contributing to implementation of therapies. However, causative genetic mutations cannot be detected in about 20% of patients. To elucidate additional genetic mutations in LQTS, we performed deep-sequencing of previously reported 15 causative and 85 candidate genes for this disorder in 556 Japanese LQTS patients. We performed in-silico filtering of the sequencing data and found 48 novel variants in 33 genes of 53 cases. These variants were predicted to be damaging to coding proteins or to alter the binding affinity of several transcription factors. Notably, we found that most of the LQTS-related variants in the RYR2 gene were in the large cytoplasmic domain of the N-terminus side. They might be useful for screening of LQTS patients who had no known genetic factors. In addition, when the mechanisms of these variants in the development of LQTS are revealed, it will be useful for early diagnosis, risk stratification, and selection of treatment.

DOI： 10.1371/journal.pone.0277242

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DOI： 10.3389/fped.2022.935167

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J waves may be observed during coronary angiography (CAG), but they have not been fully studied. We investigated the characteristics of J waves in 100 consecutive patients during CAG. The patients and their family members had no history of cardiac arrest. Approximately 60% of patients had ischemic heart disease, previous myocardial infarction, or angina pectoris, but at the time of this study, the right coronary artery was shown to be normal or patent after stenting. Electrocardiogram was serially recorded to monitor J waves and alteration of the QRS complex during CAG. In 12 patients (12%), J waves (0.249 ± 0.074 mV) newly appeared during right CAG, and in another 13 patients (13%), preexisting J waves increased from 0.155 ± 0.060 mV to 0.233 ± 0.133 mV during CAG. Left CAG induced no J waves or augmentation of J waves. Distinct alterations were observed in the QRS complex during CAG of both coronary arteries. Mechanistically, myocardial ischemia induced by contrast medium was considered to result in a local conduction delay, and when it occurred in the inferior wall, the site of the late activation of the ventricle, the conduction delay was manifested as J waves. In conclusion, J waves were confirmed to emerge or increase during angiography of the right but not the left coronary artery. Myocardial ischemia induced by contrast medium caused a local conduction delay that was manifested as J waves in the inferior wall, the site of the late activation of the ventricle.

DOI： 10.1016/j.amjcard.2021.09.035

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BACKGROUND: Two major forms of inherited J-wave syndrome (JWS) are recognized: early repolarization syndrome (ERS) and Brugada syndrome (BrS). OBJECTIVES: This study sought to assess the distinct features between patients with ERS and BrS carrying pathogenic variants in SCN5A. METHODS: Clinical evaluation and next-generation sequencing were performed in 262 probands with BrS and 104 with ERS. Nav1.5 and Kv4.3 channels were studied with the use of patch-clamp techniques. A computational model was used to investigate the protein structure. RESULTS: The SCN5A+ yield in ERS was significantly lower than in BrS (9.62% vs 22.90%; P = 0.004). Patients diagnosed with ERS displayed shorter QRS and QTc than patients with BrS. More than 2 pathogenic SCN5A variants were found in 5 probands. These patients displayed longer PR intervals and QRS duration and experienced more major arrhythmia events (MAE) compared with those carrying only a single pathogenic variant. SCN5A-L1412F, detected in a fever-induced ERS patient, led to total loss of function, destabilized the Nav1.5 structure, and showed a dominant-negative effect, which was accentuated during a febrile state. ERS-related SCN5A-G452C did not alter the inward sodium current (INa) when SCN5A was expressed alone, but when coexpressed with KCND3 it reduced peak INa by 44.52% and increased the transient outward potassium current (Ito) by 106.81%. CONCLUSIONS: These findings point to SCN5A as a major susceptibility gene in ERS as much as it is in BrS, whereas the lower SCN5A+ ratio in ERS indicates the difference in underlying electrophysiology. These findings also identify the first case of fever-induced ERS and demonstrate a critical role of Ito in JWS and a higher risk for MAE in JWS probands carrying multiple pathogenic variants in SCN5A.

DOI： 10.1016/j.jacc.2021.08.024

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Leadless pacemaker is indicated in patients with symptomatic bradycardia as an alternative therapy when transvenous pacemaker implantation is considered difficult or at high risk. The experience of implanting leadless pacemaker in patients with dextrocardia and situs inversus is limited. A 94-year-old male was transferred to our hospital due to advanced atrio-ventricular block with episode of syncope. Chest radiograph and computed tomography revealed dextrocardia with situs inversus. Emergency cardiac catheterization was performed and a temporary pacemaker was inserted, but the patient removed it due to delirium. So, a leadless pacemaker was implanted to him. Shorter time of bed-rest after the implantation and shorter hospital stay would be beneficial of implanting a leadless pacemaker. Precise anatomical evaluation would be important to perform implantation efficiently and safely.

DOI： 10.7759/cureus.17858

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AIMS: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability. METHODS AND RESULTS: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves. CONCLUSION: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.

DOI： 10.1093/eurheartj/ehab254

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DOI： 10.2169/internalmedicine.7675-21

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BACKGROUND: Pneumothorax is an extrapulmonary air accumulation within the pleural space between the lung and chest wall. Once pneumothorax acquires tension physiology, it turns into a potentially lethal condition requiring prompt surgical intervention. Common symptoms are chest pain and dyspnea; hence an electrocardiogram (ECG) is often performed in emergent settings. However, early diagnosis of pneumothorax remains challenging since chest pain and dyspnea are common symptomatology in various life-threatening emergencies, often leading to overlooked or delayed diagnosis. While the majority of left-sided pneumothorax-related ECG abnormalities have been reported, right-sided pneumothorax-related ECG abnormalities remain elucidated. CASE PRESENTATION: A 51-year-old man presented to the emergency department with acute-onset chest pain and dyspnea. Upon initial examination, the patient had a blood pressure of 98/68 mmHg, tachycardia of 100 beats/min, tachypnea of 28 breaths/min, and oxygen saturation of 94% on ambient air. Chest auscultation revealed decreased breath sounds on the right side. ECG revealed sinus tachycardia, phasic voltage variation of QRS complexes in V4-6, P-pulmonale, and vertical P-wave axis. Chest radiographs and computed tomography (CT) scans confirmed a large right-sided pneumothorax. The patient's symptoms, all the ECG abnormalities, and increased heart rate on the initial presentation resolved following an emergent tube thoracostomy. Moreover, we found that these ECG abnormalities consisted of two independent factors: respiratory components and the diaphragm level. Besides, CT scans demonstrated the large bullae with a maximum diameter of 46 × 49 mm in the right lung apex. Finally, the patient showed complete recovery with a thoracoscopic bullectomy. CONCLUSIONS: Herein, we describe a case of a large right-sided primary spontaneous pneumothorax with characteristic ECG findings that resolved following re-expansion of the lung. Our case may shed new light on the mechanisms underlying ECG abnormalities associated with a large right-sided pneumothorax. Moreover, ECG manifestations may provide useful information to suspect a large pneumothorax or tension pneumothorax in emergent settings where ECGs are performed on patients with acute chest pain and dyspnea.

DOI： 10.1186/s12890-021-01470-1

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Atrial fibrillation (AF) is known to aggregate within family and might be associated with a lower quality-of-life (QoL). We evaluated the association between a family history (FHx) of AF and patient-reported symptom burden and perception towards treatment. We performed a retrospective analysis in a cohort of 1285 newly diagnosed patients with AF. Patients completed the atrial fibrillation effect on quality of life (AFEQT) questionnaire at the time of registration and at the 1-year follow-up. Patients who had a first-degree relative with AF were classified into the FHx group. Baseline characteristics and AFEQT scores were compared between groups, and a multivariate analysis was used to evaluate the independent association between FHx and QoL. Overall, 15.9% of patients (n = 204) had a positive AF FHx. Compared to the non-FHx group, the FHx group had an earlier onset of AF (60.2 ± 12.0 years vs. 64.5 ± 12.1 years; P < 0.05) and lower AFEQT overall summary (AFEQT-OS) score at baseline (73.9 ± 17.8 vs. 77.0 ± 16.8; P < 0.05). After adjustment for clinical background, a positive FHx was independently associated with a worse QoL (changes in AFEQT-OS score = - 3.18; 95% confidence interval: - 5.67 to - 0.69; P = 0.012). No between-group difference in AFEQT-OS scores was noted at the 1-year follow-up. An FHx of AF was associated with a lower QoL, which could be improved by therapeutic intervention in patients with AF. Recognizing the presence of an FHx of AF is important to predict patient's symptom load and treatment acceptance.

DOI： 10.1007/s00380-020-01687-w

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Thyroid hormones (THs) are synthesized in the thyroid gland, and they circulate in the blood to regulate cells, tissues, and organs in the body. In particular, they exert several effects on the cardiovascular system. It is well known that THs raise the heart rate and cardiac contractility, improve the systolic and diastolic function of the heart, and decrease systemic vascular resistance. In the past 30 years, some researchers have studied the molecular pathways that mediate the role of TH in the cardiovascular system, to better understand its mechanisms of action. Two types of mechanisms, which are genomic and non-genomic pathways, underlie the effects of THs on cardiomyocytes. In this review, we summarize the current knowledge of the action of THs in the cardiac function, the clinical manifestation and parameters of their hemodynamics, and treatment principles for patients with hyperthyroid- or hypothyroid-associated heart disease. We also describe the cardiovascular drugs that induce thyroid dysfunction and explain the mechanism underlying the thyroid toxicity of amiodarone, which is considered the most effective antiarrhythmic agent. Finally, we discuss the recent reports on the involvement of thyroid hormones in the regulation of myocardial regeneration and metabolism in the adult heart.

DOI： 10.3389/fphys.2021.606931

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OBJECTIVES: This study sought to isolate arrhythmogenic Marshall bundles (MBs) by radiofrequency (RF) catheter ablation. BACKGROUND: The vein of Marshall (VOM) is surrounded by a muscular bundle called the MB. The MB is 1 of the arrhythmogenic sources of atrial fibrillation (AF) and electrically connects to either the left atrial (LA) myocardium or coronary sinus (CS) musculature. By eliminating such electric connections using RF catheter ablation, the MB might be electrically isolated. METHODS: This retrospective study included 20 patients (64 ± 10 years old, 5 women) who underwent an MB isolation for nonparoxysmal AF. After pulmonary vein isolation, we performed venography of the VOM and inserted a 2-F electrode catheter into the VOM. RF applications were delivered to eliminate the MB electrograms from both the LA and CS when the MB was considered arrhythmogenic. RESULTS: MB isolation was achieved in 14 patients (70%). Of them, complete or partial MB isolation was accomplished in 7 patients (35%) each. The average number of RF applications in the LA (35 W, 30 s) and CS (25 W, 30 s) was 15 ± 14 and 4 ± 3, respectively. No severe adverse events were observed. During a follow-up of 23 ± 11 months, 18 patients (90%) maintained sinus rhythm. CONCLUSIONS: RF applications targeting recordings from an electrode catheter in the VOM were feasible, and the MB could be electrically isolated. Elimination of the MB potentials would be a clear endpoint for patients with an arrhythmogenic MB.

DOI： 10.1016/j.jacep.2020.06.025

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DOI： 10.2169/internalmedicine.6150-20

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Our aim was to investigate the variability in physician recognition of atrial fibrillation (AF)-related symptoms, which greatly contributes to the management of AF patients. METHODS AND RESULTS: A total of 1493 newly-referredAF patients (67 ± 11 y/o, 1057 men) consecutively registered in an outpatient-based Japanese multicenter database (KiCS-AF) from September 2012 to December 2016 were analyzed. Self-reportedAF symptom burden was assessed via symptom and daily activities domains within the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire. Physician symptom under-recognition (UR) was defined as no subjective complaints recorded in the medical records despite AFEQT score of <80; and physician's apparent over-recognition (OvR) was defined as documentation of subjective complaints despite total AFEQT score of ≥80. There was poor agreement between patient-reported and physicians-estimated symptom burden (kappa 0.28, 95% CI 0.23 to 0.33). In the logistic regression analysis, age> 75 (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.62), male sex (OR, 1.82; 95% CI, 1.22-2.74), and persistent/permanent AF (OR 2.54/3.36; CI, 1.63-3.99/1.91-5.89, respectively) were predictors of UR. Conversely, heart failure (OR, 2.46; 95% CI, 1.44-4.25) and treatment in an ablation facility (OR, 1.43; 95% CI, 1.02-2.02) were associated with greater odds of OvR in addition to age, sex, and type of AF. CONCLUSIONS: Discordance in recognition of AF symptom burden by physicians was frequent in AF patients seen in outpatient management and involved both patient- and physician-related factors.

DOI： 10.1016/j.ahj.2020.03.024

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A 23-year-old female had been suffering from recurrent syncopal episodes during sleep since her childhood. She had a family history of sudden death and her QTc interval was remarkably prolonged to 537 ms A Holter ECG revealed torsade de pointes, corresponding to syncope. She was started on mexiletine and her QTc interval shortened. Her symptoms were controlled after β-blockers and Ca-blockers were added. A genetic analysis with a next generation sequencer identified a frameshift mutation at the C terminus of the KCNH2 gene. Here we present a type 2 long QT syndrome case in which mexiletine was effective.

DOI： 10.1002/joa3.12300

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Some patients with hypertrophic cardiomyopathy (HCM) develop systolic dysfunction, called the dilated phase of HCM (d-HCM), which is associated with increased morbidity and mortality. We conducted a retrospective study using an HCM database to clarify the incidence, clinical characteristics, and long-term outcomes of d-HCM. We analyzed an HCM cohort consisting of 434 patients (273 with apical HCM and 161 with non-apical HCM; 18 had obstructive HCM, 16 had dilated HCM, and 127 had other HCM) diagnosed by echocardiography in our hospital between 1991 and 2010. The follow-up period was 8.4 ± 6.7 years. The mean age at final follow-up was 67 ± 14 years, and 304 patients (70%) were men. The mean age of the 16 d-HCM patients at the initial visit was 45 ± 17 years, the age at final follow-up was 59 ± 18 years, and 13 were men. Thirteen d-HCM patients developed atrial fibrillation and six patients developed ischemic stroke. Twelve d-HCM patients were implanted with cardiac devices: one pacemaker, nine implantable cardioverter-defibrillators, and two cardiac resynchronization therapy with defibrillator. Five patients died of progressive heart failure at the age of 61 ± 23 years. The age at the initial visit and final follow-up were lower and the NYHA class, brain natriuretic peptide levels, and left ventricular function at initial evaluation were worse in the d-HCM group. Univariate analysis demonstrated that a lower age at the initial visit was associated with d-HCM (hazard ratio 0.955/1 year increase; 95% CI 0.920-0.991, P = 0.015). In our HCM cohort, the incidence of d-HCM was 4%. A high prevalence of atrial fibrillation and cerebral infarction and poor prognosis were noted in this group, despite patients undergoing medication and device implantation.

DOI： 10.2302/kjm.2018-0004-OA

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DOI： 10.1002/joa3.12247

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INTRODUCTION: Restoration of sinus rhythm (SR) by catheter ablation (CA) of atrial fibrillation (AF) improves exercise tolerance. However, it is still unclear what characteristics of patients are contributing to an improvement in exercise tolerance after CA of AF without heart failure. METHODS AND RESULTS: This study consisted of 51 consecutive patients with persistent or long-standing persistent AF without heart failure who were restored to SR for over 6 months by a successful CA. Exercise tolerance was evaluated by cardiopulmonary exercise testing before and 3 and 6 months after CA. The clinical characteristics contributing to an improvement in exercise tolerance was elucidated. The peak oxygen uptake (VO2 )% significantly increased from 101.4 ± 20.3% to 110.9 ± 19.9% 3 months after the CA (P < .001). The improvement rate in the peak VO2 % exhibited a positive correlation to the baseline brain natriuretic peptide (BNP; ρ = 0.39, P < .01), but not to the age, AF duration, left ventricular ejection fraction, or left atrial size. The linear regression analysis revealed that the baseline BNP was an independent predictor of an improvement in the peak VO2 % (coefficients = 0.32; 95% confidence interval = 0.08, 0.54; P = .01). The peak VO2 % improved significantly in the patients whose baseline BNP level was greater than 100 pg/mL, compared to the others (P < .01). These favorable findings were also observed 6 months after the CA. CONCLUSION: Elimination of persistent AF by CA was associated with an improvement in exercise tolerance. This was particularly true in patients with high BNP values at baseline.

DOI： 10.1111/jce.14149

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BACKGROUND: A lower cut-off of the oesophageal temperature (ET) during catheter ablation of atrial fibrillation (AF) should be safer, but its durability may become in question. We evaluated an ET cut-off of 38°C with an output of 25W on the posterior wall. METHODS: In 636 consecutive patients (age: 60±10years, male: 542, paroxysmal AF: 405, CHADS2 score: 0.7±0.9), an ET probe was utilised in 303 patients (259 pulmonary vein isolations [PVIs] and 44 simultaneous isolations of the posterior wall and all PVs box isolations [BOXIs]). When the ET increased to >38°C, the radiofrequency delivery was switched off and the ablation point was tagged as an "EsoTag" by the CARTO™ system (Biosense Webster, Irvine, CA, USA). We analysed the characteristics of the ablation lesions at the EsoTags with respect to the dormant conduction, gaps in the redo-session, and ablation outcome. RESULTS: EsoTags were identified in 94.6% of the left PVIs and all BOXIs, and dormant conduction at the EsoTags was identified in 12.0% and 6.8%, respectively. In 10,796 ablation points, the ablation at the EsoTags that were associated with dormant conduction had a significantly shorter duration, smaller force-time integral, and smaller Δimpedance. The duration of an ET of >38°C was significantly and positively correlated with the body mass index and negatively with the left atrial appendage flow velocity. During the redo-sessions in a 10.5±6.0months of follow-up (PVI: 14.7%, BOXI: 11.4%), reconnections at the EsoTags with dormant conduction were observed only in two patients after the PVI. The AF survival rate did not significantly differ in the presence of dormant conduction at the EsoTags (83.1% vs. 75.0%, p=0.696). There were no patients hospitalised for gastroparesis. CONCLUSIONS: Atrial fibrillation ablation utilising an oesophageal temperature cut-off of 38°C might be safe and durable.

DOI： 10.1016/j.hlc.2018.05.197

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BACKGROUND: Epicardiac conduction via the vein of Marshall (VOM) can bypass the mitral isthmus (MI) line, making MI ablation difficult. This study aimed to assess the contribution of the VOM in achieving MI conduction block. METHODS: This study included 143 consecutive patients with nonparoxysmal atrial fibrillation who underwent initial MI ablation. They were retrospectively classified into two groups, a VOM-guided group (n = 28) and a conventional group (n = 115), according to the use of a 2-Fr electrode catheter inserted in the VOM. The acute success rate of achieving MI block and the ablation data were assessed. When the bidirectional block was verified exclusively in the VOM or coronary sinus (CS) electrodes, we defined it as a pseudo MI block. In the VOM-guided group, we ascertained the complete MI block, verified both in the VOM and CS electrodes. RESULTS: In the VOM-guided group, the pseudoblock was observed in 33.3% of the patients during MI ablation. With significantly less radiofrequency energy (19 322.6 ± 11 352.8 vs 25 389.3 ± 19 951.9, P = 0.04), we achieved a similar level of success rate in MI ablation in the VOM-guided group (96.4% vs 91.3%, P = 0.36). Notably, after achieving complete MI block, atrial burst pacing induced two perimitral flutters in the VOM-guided group, which were successfully terminated by the additional radiofrequency application. CONCLUSIONS: Assessment of electrical conduction through the VOM could clarify the existence of a pseudo MI conduction block. However, the existence of a slow conduction through the MI could be detected only after induction of perimitral atrial tachycardia with atrial programmed stimulation.

DOI： 10.1111/pace.13640

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Importance: The clinical characteristics and outcomes of women and men with atrial fibrillation (AF) are reported to be different. However, whether sex-related differences extend to patients' symptom burden and perceived quality of life (QOL) or the management pattern of AF has been rarely studied, particularly in Asian countries. Objective: To assess the differences in symptoms, treatment, and QOL between Japanese female and male patients with AF. Design, Setting, and Participants: Retrospective cohort study using data from the multicenter outpatient registry Keio Interhospital Cardiovascular Studies-Atrial Fibrillation (KiCS-AF), which collects information regarding health status and the treatment of patients with newly diagnosed or referred AF. One-year follow-up data were available for 1534 patients at 11 referral centers in the Tokyo, Japan, area who were enrolled between September 2012 and December 2015. All data available up to the 1-year follow-up examination through July 31, 2017, were included. Main Outcomes and Measures: Sex, symptoms, AF treatment, and QOL as determined by Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaires at their initial visit and 1 year later. Results: Of 1534 patients, 1076 (70.1%) were men. Compared with men, women were more likely to be older (median age, 73 years [interquartile range {IQR}, 65-78 years] vs 65 years [IQR, 57-73 years], P < .001) and have higher median brain-type natriuretic peptide levels (102.8 pg/mL [IQR, 47.3-235.5 pg/mL] vs 74.1 pg/mL [IQR, 28.5-150.5 pg/mL], P < .001). Women also had lower median AFEQT overall summary scores than men (75 [IQR, 61-85] vs 80 [IQR, 69-90]; P < .001) but similar treatment satisfaction at baseline. During follow-up, women were less likely to be treated with a rhythm control strategy (48.1% [n = 214] vs 58.0% [n = 621], P < .001), including catheter ablation of AF (adjusted hazard ratio, 0.77 [95% CI, 0.62-0.95]; P = .02). At 1-year follow-up, women and men had improved QOL scores, regardless of their baseline characteristics (eg, age or brain-type natriuretic peptide levels) or treatment strategies, yet the sex gap persisted and grew (adjusted change in AFEQT overall summary score during 12 months, 5.89 [95% CI, 2.24-9.54] in women vs 8.94 [95% CI, 5.59-12.30] in men; P = .02). Conclusions and Relevance: In contemporary Japanese clinical practice among unselected patients with AF, women were initially seen with greater QOL impairment, and the sex gap grew 1 year after presentation. The present study underscores the need for focused efforts to better understand and close this observed sex gap over the initial year of treatment for patients with AF.

DOI： 10.1001/jamanetworkopen.2019.1145

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Importance: Long QT syndrome (LQTS) is caused by several ion channel genes, yet risk of arrhythmic events is not determined solely by the responsible gene pathogenic variants. Female sex after adolescence is associated with a higher risk of arrhythmic events in individuals with congenital LQTS, but the association between sex and genotype-based risk of LQTS is still unclear. Objective: To examine the association between sex and location of the LQTS-related pathogenic variant as it pertains to the risk of life-threatening arrhythmias. Design, Setting, and Participants: This retrospective observational study enrolled 1124 genotype-positive patients from 11 Japanese institutions from March 1, 2006, to February 28, 2013. Patients had LQTS type 1 (LQT1), type 2 (LQT2), and type 3 (LQT3) (616 probands and 508 family members), with KCNQ1 (n = 521), KCNH2 (n = 487) and SCN5A (n = 116) genes. Clinical characteristics such as age at the time of diagnosis, sex, family history, cardiac events, and several electrocardiographic measures were collected. Statistical analysis was conducted from January 18 to October 10, 2018. Main Outcomes and Measures: Sex difference in the genotype-specific risk of congenital LQTS. Results: Among the 1124 patients (663 females and 461 males; mean [SD] age, 20 [15] years) no sex difference was observed in risk for arrhythmic events among those younger than 15 years; in contrast, female sex was associated with a higher risk for LQT1 and LQT2 among those older than 15 years. In patients with LQT1, the pathogenic variant of the membrane-spanning site was associated with higher risk of arrhythmic events than was the pathogenic variant of the C-terminus of KCNQ1 (HR, 1.60; 95% CI, 1.19-2.17; P = .002), although this site-specific difference in the incidence of arrhythmic events was observed in female patients only. In patients with LQT2, those with S5-pore-S6 pathogenic variants in KCNH2 had a higher risk of arrhythmic events than did those with others (HR, 1.88; 95% CI, 1.44-2.44; P < .001). This site-specific difference in incidence, however, was observed in both sexes. Regardless of the QTc interval, however, female sex itself was associated with a significantly higher risk of arrhythmic events in patients with LQT2 after puberty (106 of 192 [55.2%] vs 19 of 94 [20.2%]; P < .001). In patients with LQT3, pathogenic variants in the S5-pore-S6 segment of the Nav1.5 channel were associated with lethal arrhythmic events compared with others (HR, 4.2; 95% CI, 2.09-8.36; P < .001), but no sex difference was seen. Conclusions and Relevance: In this retrospective analysis, pathogenic variants in the pore areas of the channels were associated with higher risk of arrhythmic events than were other variants in each genotype, while sex-associated differences were observed in patients with LQT1 and LQT2 but not in those with LQT3. The findings of this study suggest that risk for cardiac events in LQTS varies according to genotype, variant site, age, and sex.

DOI： 10.1001/jamacardio.2018.4925

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Language：English   Publisher：(一社)日本循環器学会  

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Language：English   Publisher：(一社)日本循環器学会  

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DOI： 10.1016/j.amjcard.2019.01.015

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BACKGROUND: J waves develop during hypothermia, but the dynamicity of hypothermia-induced J waves is poorly understood. OBJECTIVE: The purpose of this study was to investigate the mechanism of the rate-dependent change in the amplitude of hypothermia-induced J waves. METHODS: Nineteen patients with severe hypothermia were included (mean age 70 ± 12 years; 16 men [84.2%]). The rectal temperature at the time of admission was 27.8° ± 2.5°C. In addition to prolonged PR, QRS complex, and corrected QT intervals, the distribution of prominent J waves was widespread in all 19 patients. RESULTS: Nine patients showed changes in RR intervals. When the RR interval shortened from 1353 ± 472 to 740 ± 391 ms (P = .0002), the J-wave amplitude increased from 0.50 ± 0.29 to 0.61 ±0.27 mV (P = .0075). The J-wave amplitude increased in 7 patients (77.8%) and decreased in 2 patients (22.2%) after short RR intervals. The augmentation of J waves at short RR intervals was associated with a significant prolongation of ventricular activation time (35 ± 5 ms vs 46 ± 5 ms; P = .0020), suggesting accentuated conduction delay. Increased conduction delay at short RR intervals was suggested to accentuate the phase 1 notch of the action potential and J waves in hypothermia. None developed ventricular fibrillation, and in 2 of 9 patients with atrial fibrillation, atrial fibrillation persisted after rewarming to normothermia. CONCLUSION: J waves in severe hypothermia were augmented after short RR intervals in 7 patients as expected for depolarization abnormality, whereas 2 patients showed a bradycardia-dependent augmentation as expected for transient outward current-mediated J waves. Increased conduction delay at short RR intervals can be responsible for the accentuation of the transient outward current and J waves during severe hypothermia.

DOI： 10.1016/j.hrthm.2018.07.024

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A 62-year-old female had suffered from recurrent syncopal episodes triggered by physical and emotional stress since childhood. She had no family history of sudden death. An intensive examination could not detect any structural disease, and exercise stress testing provoked polymorphic ventricular ectopy followed by polymorphic ventricular tachycardia accompanied with syncope leading to a diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). A genetic analysis with a next generation sequencer identified a homozygous W361X mutation in the CASQ2 gene. Careful history taking disclosed that her parents had a consanguineous marriage. Here we present a Japanese patient with a recessive form of CPVT.

DOI： 10.1155/2019/9056596

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OBJECTIVES: This randomized study compared uninterrupted rivaroxaban therapy with warfarin therapy as prophylaxis against catheter ablation (CA)-induced asymptomatic cerebral infarction (ACI) and identified the risk factors of rivaroxaban. BACKGROUND: The reported incidence of ACI during CA for atrial fibrillation (AF) remains at 10% to 30%, and periprocedural oral anticoagulation could affect this incidence. METHODS: Patients with nonvalvular AF undergoing radiofrequency CA were randomly assigned to receive either uninterrupted rivaroxaban or warfarin as periprocedural anticoagulation therapy. CA was performed after at least 1 month of adequate anticoagulation. Cerebral magnetic resonance imaging (MRI) was performed within 2 weeks before and 1 day after CA to detect ACI. RESULTS: A total 132 patients were enrolled; 127 (median: 60.0 years of age; 83.5% males; 64.6% incidence of paroxysmal AF) complied with the study protocol and were analyzed; 64 patients received rivaroxaban, and 63 patients received warfarin. The rates of CA-induced ACI in the rivaroxaban group (15.6% [10 of 64 patients]) were similar to those in the warfarin group (15.9% [10 of 63 patients]; p = 1.000). No thromboembolic events developed; no differences in major or nonmajor bleeding rates were observed between the 2 drug groups (3.1% vs. 1.6%, respectively, or 18.8% vs. 19.0%, respectively). Multiple regression analysis indicated that the presence of deep and subcortical white matter hyperintensity (p = 0.002; odds ratio [OR]: 5.323) and the frequency of cardioversions (p = 0.016; OR: 1.250) were associated with the incidence of ACI. CONCLUSIONS: No notable differences were found between the incidence of CA-induced ACI in the rivaroxaban group and that in the warfarin group in this randomized study.

DOI： 10.1016/j.jacep.2018.08.003

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DOI： 10.1016/j.ijcard.2018.06.049

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Background Brugada syndrome ( BS ) is known to be 9 times more prevalent in males than females. However, little is known about the development of sick sinus syndrome in female members with familial BS . Methods and Results Familial BS patients and family members, both from our institutions and collaborating sites that specialize in clinical care of BS , participated in this study. We collected information on their clinical and genetic background, along with the inheritance patterns of BS . Detailed information on each case with familial BS is described. A total of 7 families, including 25 BS patients (12 females and 13 males), were included. Seven were probands and 18 were family members. Ten out of the 12 female patients and none of the 13 male patients developed sick sinus syndrome. Sudden death or spontaneous ventricular fibrillation occurred in 7 out of 13 male patients and 2 out of 12 female patients. Conclusions Familial BS existed in which female patients developed sick sinus syndrome but male patients did not. Some of those female patients with sick sinus syndrome had unrecognized BS . Information should be collected not only regarding a family history of sudden death or BS , but also whether a pacemaker was implanted in female members.

DOI： 10.1161/JAHA.118.009387

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.hrtlng.2018.08.010

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A 50-year-old woman visited the emergency department with a high fever due to pneumonia. Incessant monomorphic ventricular tachycardia occurred and was terminated by intravenous lidocaine. Her ECG during sinus rhythm demonstrated ST segment elevation suggestive of Brugada syndrome (BS). An intensive examination could not detect any structural disease, and typical coved-type ST elevation was unmasked by a pilsicainide injection leading to a diagnosis of BS. An ICD was implanted for secondary prevention of ventricular arrhythmia. The patient has been free from any recurrences of arrhythmia for 3 years.

DOI： 10.1002/joa3.12068

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INTRODUCTION: We aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. METHODS: Before catheter ablation, 197 consecutive AF patients (age: 60 ± 9 years, body mass index; 25.0 ± 3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. RESULTS: The mean apnea-hypopnea index (AHI) was 17.7 ± 11.9, with 135 AF patients having an AHI ≥10 (68.5%). Patients with an AHI ≥10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI ≥10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, P = 0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. CONCLUSIONS: The prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.

DOI： 10.1016/j.ijcard.2018.01.103

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

Aims To confirm the presence of tachycardia-induced slur or notch in the terminal portion of the QRS complexes in a general patient population. Methods and results A tachycardia-induced J wave was defined as a slur or notch in the terminal portion of the QRS complexes newly induced at short RR intervals during atrial premature contractions (APCs) or atrial electrical stimulation in the electrophysiological study (EPS). Twenty-three out of 2000 patients with general diseases were involved. All patients with aborted sudden cardiac death, ventricular fibrillation or a family history of sudden cardiac death were excluded. The mean age was 72 ± 9 years, and 11 patients were male (47.8%). When the RR interval was shortened from 821 ± 142 ms to 464 ± 52 ms in the conducted APCs (P &lt
0.0001), J waves became diagnostic (0.02 ± 0.03 mV to 0.20 ± 0.07 mV, P &lt
0.0001). J waves were confined to the inferior leads in 22 (95.7%) patients and were notched in 11 (47.8%) and slurred in 12 (52.2%) patients. The induction of J waves was accompanied by visible changes of the QRS morphology. When the post-APC RR interval was prolonged to 992 ± 305 ms (P = 0.0154 vs. baseline), the J waves were similar to baseline levels. During the EPS, J wave induction was confirmed during atrial stimulation. There were no characteristic clinical or ECG features in the patients with tachycardia-induced J waves. Conclusions J waves can be newly induced by short RR intervals in a general patient population, and a conduction delay is the likely mechanism causing such J waves.

DOI： 10.1093/europace/eux062

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Background: Balloon pulmonary angioplasty (BPA) is a treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results: In 60 patients with CTEPH, we examined the hemodynamic data before and after BPA. In addition, the sequential ECG findings for right ventricular hypertrophy (RVH) were assessed. The mean pulmonary arterial pressure (mPAP) decreased from 38 ± 11 to 20 ± 4 mm Hg (p < 0.05). The ROC analysis showed that the S waves in V5, R waves in V1 + S waves in V5, S waves in I, and QRS axis were significant predictors of an mPAP ≧ 30 mm Hg (AUC > 0.75, p < 0.01). The predictive values for the mPAP before the BPA were the S and R waves in lead V6, and P waves in lead II (33.417 + 0.078 × P in II - 0.10 × R in V6 + 0.012 × S in V6). The change in the mPAP (ΔmPAP) correlated with the change in the amplitudes of the ECGs: ΔS wave in lead I (R = 0.544, p < 0.001), ΔR in V1 + S in V5 (R = 0.476, p < 0.001), and ΔP wave in II (R = 0.511, p < 0.001). At 6 months of follow-up, the improvement in an R in V1 + S in V5 of ≧10 mm implied a better functional status. Conclusion: BPA therapy reduced the pulmonary arterial pressure in patients with CTEPH and was associated with an improvement in the ECG findings related to RVH.

DOI： 10.1016/j.ijcha.2018.05.003

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DOI： 10.1161/CIRCINTERVENTIONS.117.006244

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BACKGROUND: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). METHODS AND RESULTS: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P>0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P>0.05). CONCLUSIONS: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

DOI： 10.1161/JAHA.117.006612

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1161/CIRCINTERVENTIONS.117.005812

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Background: For perimitral atrial flutter (PMFL) developing after catheter ablation of atrial fibrillation (AF), to create a complete conduction block at the mitral isthmus (MI) is mandatory to terminate it, however, it is still challenging.
Methods: This study consisted of 80 patients (74 male, 61 +/- 8.1 years) undergoing MI ablation. After a circular mapping catheter was positioned at the neck of the left atrial appendage (LAA), the MI ablation was performed on the MI line just below the LAA neck targeting the earliest activation recording site of the LAA catheter during pacing from the coronary sinus (CS). When ablation during CS pacing was not successful, an RF delivery during LAA pacing was applied targeting the earliest activation site just below the MI line. If the endocardial approach failed, an RF application inside the CS was attempted.
Results: With the endocardial approach, acute success was achieved in 51/80 patients (64%). Additional epicardial ablation from the CS was performed in 26/29 (90%) endocardially unsuccessful patients and conduction block at the MI was achieved in 21/26 (81%). Overall, complete conduction block at the MI was achieved in 72/80 patients (90%). At a mean follow-up of 16 +/- 6 months, 20 patients (25%) had recurrence of atrial arrhythmias (AT: 12, AF: 8), and 10 (AT: 7, AF : 3) underwent a second procedure in which an LMI block line was completed in 3 (33%). PMFL was diagnosed in 6 out of 7 AT patients. No complications were observed.
Conclusions: Creating linear lesions just beneath the neck of the LAA was highly successful under the guidance of a circular mapping catheter in the LAA using a steerable sheath. An RF application from the CS was needed in less than half of the cases.

DOI： 10.18632/oncotarget.17092

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

Performance measures (PMs) are used to accelerate translation of scientific evidence into clinical practice. However, it remains unknown how they are applied in the real world and whether the compliance to these metrics will lead to improved patient's outcome in atrial fibrillation (AF). Within the Japanese multicenter AF registry (n = 1,874), adherence of the AF PMs (based on 2016 American Heart Association/American College of Cardiology criteria) and its association with quality of life scaling and clinical outcomes was evaluated. The patient was deemed "adherent" when all applicable components of the PMs for outpatient settings (CHA(2)DS(2)-VASc risk score documentation [PM-4], anticoagulation prescribed [PM-5], and monthly international normalized ratio (INR) for warfarin treatment [PM-6]) were satisfied. The Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire was assessed at baseline and 1 year. About a half of patients (46.1%) were adherent to the AF PMs. PMs were more frequently achieved in patients managed with rhythm control compared with rate control. The achievement rate for each component was 53.9% for PM-4, 85.6% for PM-5, and 90.3% for PM-6, respectively. Although AFEQT global scores at baseline were similar (median 79.2 [interquartile ranges 66.7 to 88.5] vs 77.1 [64.8 to 88.0], p = 0.227), AFEQT global scores at 1-year follow-up were significantly greater in adherence group than those in nonadherence group (89.2 [78.5 to 96.6] vs 86.7 [76.7 to 95.0], p = 0.021). This tendency was consistent regardless of therapeutic strategies. There remains an important opportunity to improve the quality of care in patients with AF. Adherence to the AF PMs might lead to the improvement of patient's quality of life. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2017.05.029

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Language：English   Publisher：WILEY  

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a useful option for patients with a single ventricle (SV) in which transvenous leads are contraindicated because of intracardiac shunts. We report a case in which a right parasternal lead placement was indicated for an S-ICD in a resuscitated patient with an SV. There were significant changes in the magnitude of R to T waves ratio in the right compared to the left parasternal lead position. Screening in the right parasternal position is effective for selecting appropriate patients with congenital heart disease for S-ICD implantations.

DOI： 10.1111/pace.13046

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background- To know the underlying mechanisms of J waves, the response to atrial pacing was studied in patients with idiopathic ventricular fibrillation (IVF) and patients with non-IVF.
Methods and Results- In 8 patients with IVF, the J- wave amplitude was measured before, during, and after atrial pacing. All patients had episodes of ventricular fibrillation without structural heart disease. The responses of J waves were compared with those of the 17 non-IVF control subjects who revealed J waves but no history of cardiac arrest and underwent electrophysiological study. The IVF patients were younger than the non-IVF patients (28 +/- 10 versus 52 +/- 14 years, respectively; P= 0.002) and had larger J waves with more extensive distribution. J waves decreased from 0.35 +/- 0.26 to 0.22 +/- 0.23 mV (P= 0.025) when the RR intervals were shortened from 782 +/- 88 to 573 +/- 162 ms (P= 0.001). A decrease (= 0.05 mV) in the J-wave amplitude was observed in 6 of the 8 patients. In addition, 1 patient showed a distinct reduction of J waves in the unipolar epicardial leads. In contrast, J waves were augmented in the 17 non-IVF subjects from 0.27 +/- 0.09 to 0.38 +/- 0.10 mV (P&lt; 0.001): augmented in 9 and unchanged in the 8 subjects. The different response patterns of J waves to rapid pacing suggest different mechanisms: early repolarization in IVF patients and conduction delay in non-IVF patients.
Conclusions- The response to atrial pacing was different between the IVF and non- IVF patients, which suggests the presence of different mechanisms for the genesis of J waves.

DOI： 10.1161/CIRCEP.117.005214

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DOI： 10.1016/j.jacep.2016.12.013

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DOI： 10.1016/j.hrcr.2017.03.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

A 16-year-old boy with long QT syndrome type 3 (LQT3) was admitted for decompensated heart failure resulting from dilated cardiomyopathy (DCM). His brother was also diagnosed with LQT3 and DCM. A comprehensive genetic analysis identified a novel SCN5A missense mutation-p.Q371E-in these 2 affected living family members. It might be important to suspect the coexistence of DCM and LQT3 (which is rare according to previous articles) in cases with this novel SCN5A missense mutation.

DOI： 10.1016/j.cjca.2016.10.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Differences in the methodologies for evaluating atrial fibrillation (AF) ablation outcomes should be evaluated. In the present study, we compared the AF ablation outcomes among periodic clinic electrocardiography (ECG), 24-h Holter ECG, and telemonitoring ECG to evaluate the differences among these methods. In addition, we evaluated the AF-free survival rate for each method with different durations of the blanking period. A total of 30 AF patients were followed up for 6 months after initial catheter ablation, with clinic ECG on every clinic visit, monthly 24-h Holter ECG, and telemonitoring ECG twice daily and upon symptoms. AF relapse was defined as AF or atrial tachycardia detected with any of the methods. Two patients dropped out of the study, and 28 patients were followed up for 8.8 +/- 2.7 months. Patients underwent 3.6 +/- 0.8 clinic ECG, 5.1 +/- 0.8 Holter ECG, and 273 +/- 68 telemonitoring ECG examinations. During the first, second, third, fourth, fifth, and sixth months of follow-up, Holter ECG detected relapses in 11.1, 8.3, 11.5, 15.4, 4.2, and 4.8 % of patients and telemonitoring ECG detected relapses in 32.1, 25.0, 25.0, 17.9, 28.6, and 17.9 % of patients, respectively. When no duration was set for the blanking period, the AF-free survival rate was significantly lower with telemonitoring ECG (46.4 %) than with Holter ECG (78.6 %, P = 0.013) or clinic ECG (85.7 %, P = 0.002). In addition, when the duration of the blanking period was set to 3 months, the AF-free survival rate was significantly lower with telemonitoring ECG than with clinic ECG (92.9 vs. 71.4 %, P = 0.041). The AF ablation outcomes with twice-daily telemonitoring ECG might differ from those with clinic ECG when the duration of the blanking period is 0-3 months. A follow-up based solely on clinic ECG might underestimate AF recurrence.

DOI： 10.1007/s00380-016-0866-2

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Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed somatic cells from three ATS patients to generate induced pluripotent stem cells (iPSCs). Multi-electrode arrays (MEAs) were used to record extracellular electrograms of iPSC-derived cardiomyocytes, revealing strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Ca2+ imaging of cells loaded with the Ca2+ indicator Fluo-4 enabled us to examine intracellular Ca2+ handling properties, and we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes than in control-iPSC-derived cardiomyocytes. Drug testing using ATS-iPSC-derived cardiomyocytes further revealed that antiarrhythmic agent, flecainide, but not the sodium channel blocker, pilsicainide, significantly suppressed these irregular Ca2+ release and arrhythmic events, suggesting that flecainide's effect in these cardiac cells was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig cardiac ventricular myocytes confirmed that flecainide could directly affect the NCX current (INCX). ATS-iPSC-derived cardiomyocytes recapitulate abnormal electrophysiological phenotypes and flecainide suppresses the arrhythmic events through the modulation of INCX.

DOI： 10.1016/j.bbrep.2017.01.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.hrcr.2016.08.008

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2016.11.052

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Background: We aimed to clarify the cost-effectiveness of an expensive combination therapy for atrial fibrillation (AF) using both catheter ablation and dabigatran compared with warfarin at each CHADS(2) score for patients in Japan.
Methods: A Marlcov model was constructed to analyze costs and quality-adjusted life years associated with AF therapeutic options with a time horizon of 10 years. The target population was 60-year-old patients with paroxysmal AF. The indication for anticoagulation was determined according to the Japanese guideline. Anticoagulation-related data were derived from the RE-LY study and the AF recurrence rate was set at 2.7% per month during the first 12 months and at 0.40% per month afterwards. Stroke risk was determined according to AF recurrence, anticoagulation, and CHADS(2) score. The risks for stroke recurrence' and stroke death were also considered. Costs were calculated from the healthcare payer's perspective, and only direct medical costs were included.
Results: Warfarin was the most preferred option for patients with a CHADS(2) score of 0 from a health economics aspect. Ablation under warfarin was preferred for a CHADS(2) score of 1-3, while ablation under dabigatran was preferred for a CHADS(2) score &gt;= 4. The quality of life score for AF had the largest impact on the incremental cost-effectiveness ratios in the analysis between the anticoagulation arm and the anticoagulation + ablation arm for a CHADS(2) score of 2. Within the range of the Japanese willingness to-pay threshold ((sic)5,000,000), the ablation + warfarin arm became the best option with its probability of 81.7% for a CHADS(2) score of 2; the dabigatran + ablation arm was the most preferred option with its probability of 56.1% for a CHADS(2) score of 4.
Conclusions: Ablation under dabigatran therapy is an expensive therapeutic option, but it might benefit patients with a low quality of life and a high CHADS(2) score. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2016.01.008

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Background: Atrioventricular conduction disturbances can develop after transcatherter aortic valve implantations (TAVIs) with balloon-expandable valves because the conduction system exists adjacent to the aortic valve. However, the clinical consequence of patients with new onset conduction disturbances is not clear.
Objective: This study aimed to assess the incidence and progress of new-onset conduction disturbances following TAVIs and the cardiac function evaluated by echocardiography. Methods: This study consisted of 90 consecutive patients that underwent TAVIs with Edwards SAPIEN XT valves in a single center. Atrioventricular conduction system disturbances were assessed by electrocardiography and echocardiography up to 6 months post TAVI
Results: Twenty patients (22%) developed new onset complete left bundle branch block (CLBBB) or received pacemaker implantations (PMIs) during the follow-up. At 6 months after the procedure, 4 patients underwent PMIs for complete AV block (CAVB), and 4 patients had persistent CLBBB. Those that developed CLBBB and AVB had a higher morbidity from hypertension and lower estimated glomerular filtration rate (eGFR). The ECG, TTE, and CT parameters did not differ between the two groups. The ratio of the valve and LVOT area was significantly associated with a higher cumulative risk of events (HR, 3.005; 95% Cl, 1.034-8.736; P &lt; 0.05).
Conclusions: Up to 20% of patients developed new CLBBB or CAVB and more than half were expected to recover. However, it required attention because approximately 40% were persistent. The ratio of the valve to LVOT area was an independent predictor. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2016.11.063

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BACKGROUND: The monitoring of the effects of direct oral anticoagulants may be beneficial during emergencies and adverse events. We aimed to explore direct oral anticoagulant monitoring in "real-world" settings, in which monitoring methods are limited and loading time can be estimated based on only patient reports. METHODS: In 164 patients, plasma anti-Xa activity was assessed using a STA®-Liquid Anti-Xa reagent (Diagnostica Stago, Asnieres, France), and prothrombin time was measured using HemosIL® RecombiPlasTin 2G (Instrumentation Laboratory, Bedford, MA, USA). The loading time was calculated according to the previous dosing time reported by the patient. In the clinic setting, rivaroxaban and apixaban were administered to 103 patients with atrial fibrillation and a blood sample was tested once during a clinic visit. In the hospitalization setting, edoxaban was administered to 61 patients undergoing arthroplasty for prophylaxis of a venous thrombosis and blood samples were tested 3 and 18 h after the last intake. RESULTS: Plasma Xa activity in the clinical setting ranged widely (rivaroxaban: 1.1-424.4 ng/mL, apixaban: 15.4-469.2 ng/mL) during the 11.7 ± 7.0 h following the previous dose. The values varied over a wide range (up to a factor of 2) at the same loading time, especially around the peak period. The plasma anti-Xa activity of rivaroxaban and apixaban showed linear correlations with prothrombin time (R2 = 0.828 and 0.717, respectively). Edoxaban administration prolonged the prothrombin time by only 1.6 ± 1.1 s from the trough to the peak, to a degree that was negatively correlated with age, but not with plasma creatinine level, creatinine clearance, or body mass index. CONCLUSION: In real-world settings, plasma anti-Xa monitoring should be interpreted considering the wide variations in data, reflecting the variability in patient-reported loading time and interpatient variability.

DOI： 10.1177/2050312117734773

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DOI： 10.1016/j.ijcard.2016.08.013

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DOI： 10.1016/j.jcin.2016.07.028

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SCN5A is abundant in heart and has a major role in I-Na. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each beta-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that I-Na of mutated SCN5A is decreased and SCN3B augmented INa of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties.

DOI： 10.1038/srep34198

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In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

DOI： 10.1016/j.ijcha.2016.05.008

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With the new era of multi-tip radiofrequency or balloon ablation catheters replacing the point-to-point ablation strategy, we aimed to determine the feasibility of a ring-laser catheter ablation technology to electrically isolate the superior vena cava (SVC) by exploring the advantages of the limitless catheter tip size possibly with the photodynamic therapy (PDT)-mediated ablation.
We developed a first-generation prototype of a circular-laser-mapping catheter by fitting a 7 cm plastic optical fibre onto a circular variable-loop Lasso (TM) mapping catheter. Following SVC venography, both the laser catheter and another ring catheter for monitoring the SVC potentials were placed at the SVC. After the systemic infusion of a photosensitizer (talaporfin sodium), we initiated the irradiation with an output of 1 W in three canines and 0.3 W in four. The creation of electrical isolation as well as occurrence of phrenic nerve injury, sinus node injury, and SVC stenosis were evaluated before, immediately after, and 1 month after the procedure. A PDT-mediated SVC isolation was successfully performed in all seven canines. The isolation was completed with a laser irradiation of 70.4 +/- 71.4 J/cm under 30.9 +/- 5.0 A mu g/mL of a photosensitizer without any sinus node injury, phrenic nerve palsy, or SVC stenosis in both the acute and chronic evaluations. The minimum isolation time of 270 s was not correlated with the laser input power or the photosensitizer concentration.
The electrical SVC isolation was successfully and instantly achieved using the PDT laser-ring catheter without any complications.

DOI： 10.1093/europace/euv016

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The American Heart Association Scientific Sessions were held in Orlando on November 7-15, 2015. The meeting attracted more than 18,000 participants, including physicians, research scientists, students, and paramedical personnel, from more than 100 countries. Sessions over the 5 days included a comprehensive and unparalleled education delivered via more than 5,000 presentations, with 1,000 invited faculty members and 4,000 abstract presentations from the world leaders in cardiovascular disease. It also displayed the newest cardiovascular technology and resources by more than 200 exhibitors. There were 19 trials scheduled in 6 late-breaking clinical trial sessions. The Systolic Blood Pressure Intervention Trial (SPRINT) aimed to determine the most appropriate targets for the systolic blood pressure among persons without diabetes. A total of 9,361 persons with systolic blood pressure of &gt;= 130 mmHg and an increased cardiovascular risk, but without diabetes, were randomly assigned to a target systolic blood pressure of &lt;120 mmHg (intensive treatment) or a target of &lt;140 mmHg (standard treatment). A significantly lower rate of the primary composite outcome and all-cause mortality in the intensive-treatment group than in the standard-treatment group was observed. Summaries and overviews of the late-breaking trials, clinical science special report sessions, and sessions to which members of the Japanese Circulation Society contributed are presented.

DOI： 10.1253/circj.CJ-15-1272

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Background-Although automated external defibrillators (AEDs) have contributed to a better survival of out-of-hospital cardiac arrests, there have been reports of their malfunctioning. We investigated the diagnostic accuracy of commercially available AEDs using surface ECGs of ventricular fibrillation (VF), ventricular tachycardia (VT), and supraventricular tachycardia (SVT).
Methods and Results-ECGs(VF 31, VT 48, SVT 97) were stored during electrophysiological studies and transmitted to 4 AEDs, the LifePak CR Plus (CR Plus), HeartStart FR3 (FR3), and CardioLife AED-2150 (CL2150) and -9231 (CL9231), through the pad electrode cables. For VF, the CL2150 and CL9231 advised shocks in all cases, and the CR Plus and FR3 advised shocks in all but one VF case. For VTs faster than 180 bpm, the ratios for advising shocks were 79%, 36%, 89%, and 96% for the CR Plus, FR3, CL2150, and CL9231, respectively. The FR3 and CR Plus did not advise shocks for narrow QRS SVTs, whereas the CL9231 tended to treat high-rate tachycardias faster than 180 bpm even with narrow QRS complexes. The characteristics of the shock advice for the FR3 differed from that for the CL9231 (kappa coefficient [kappa]=0.479, P&lt;0.001), and the CR Plus and CL2150 had characteristics somewhere between the 2 former AEDs (kappa=0.818, P&lt;0.001).
Conclusions-Commercially available AEDs diagnosed VF almost always correctly. For VT and SVT diagnoses, a discrepancy was evident among the 4 investigated AEDs. The differences in the arrhythmia diagnosis algorithms for differentiating SVT from VT were thought to account for these differences.

DOI： 10.1161/JAHA.115.002465

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Introduction: Lead failures (LFs) are one of the most common complications in patients implanted with cardiovascular implantable electronic devices. LFs often cause serious secondary complications such as inappropriate ICD shocks or asystole. This study aimed to identify the clinical factors associated with the occurrence of LFs.
Methods: A total of 735 consecutive device implantations (mean age 67 +/- 15 years, males 64%) performed at a single university hospital setting from 1997 to 2014 were included. The implanted devices consisted of 421 pacemakers, 250 implantable cardioverter defibrillators (ICD), 9 cardiac resynchronization therapy pacemakers (CRT-P), and 55 CRT defibrillators (CRT-D). The primary endpoint was the development of an LF.
Results: During a mean duration of 5.8 +/- 4.3 years, 38 LFs developed in 31 patients (mean age 56 +/- 14 years). LFs included 32 ICD (7 Sprint Fidelis, 2 Riata), and 6 pacing leads. Nine patients received inappropriate ICD shocks and 1 had syncope due to an LF. All patients underwent lead reinsertions with device replacements. Eight patients required opposite site implantations due to venous occlusions. The predictive factors of LFs were the age, male sex, taller body length, ICD vs. pacemaker, lesser lead number, extra-thoracic puncture of the axillary vein vs. a cut-down of the cephalic vein, use of recalled leads and patients with idiopathic ventricular fibrillation (IVF) and Brugada syndrome (BrS).
Conclusion: LFs occurred mainly with ICD leads. A lesser age, the puncture method, lead model, and diagnosis of IVF/BrS were associated with the development of LFs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2015.07.055

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Aims Accumulating data show the efficacy of catheter ablation (CA) for atrial fibrillation (AF); however, postoperative recurrence is not uncommon. The aim of this study was to identify predictors of AF recurrence in patients undergoing CA.
Methods and results We studied 100 patients with symptomatic paroxysmal (68) or persistent (32) AF who underwent CA preceded by transthoracic echocardiographic examination. Of these, 50 had sinus rhythm during echocardiography (Group NSR) and 50 had AF rhythm (Group AF). The left atrial (LA) strain was measured by two-dimensional speckle tracking echocardiography. Echocardiographic parameters were compared between the patients with AF recurrence and no recurrence. During 12 months of follow-up, 26 of 100 patients (11 in Group NSR and 15 in Group AF) had AF recurrence; these patients had significantly longer AF duration, a lower LA global strain (LA-GS), lower LA lateral total strain (LA-LS), and larger maximum LA volume index (LAVI(max)) than those who maintained sinus rhythm. Multivariate logistic regression identified basal LA-LS and LAVImax as independent predictors of AF recurrence. Furthermore, receiver operating characteristic analyses revealed that basal LA-LS was the most useful parameter for predicting AF recurrence [area under the curve (AUC): 0.84 vs. 0.74 in LAVI(max)]. Subanalyses showed that LAVI(max) was another independent predictor of AF recurrence in Group AF, but not in Group NSR, while basal LA-LS was a significant predictor in both groups.
Conclusion LA myocardial function assessed by basal LA-LS could predict AF recurrence after CA. Notably, such an assessment could be applicable even during AF rhythm, suggesting its convenience in the clinical setting without defibrillation before analysis.

DOI： 10.1093/ehjci/jev028

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Aims Photodynamic therapy (PDT) is based on non-thermal injury mediated by singlet oxygen species and is used clinically in cancer therapy. In our continuing efforts to apply this technology to cardiac catheter ablation, we clarified the optimal condition for creating PDT-mediated lesions using a laser catheter.
Methods and results In a total of 35 canines, we applied a laser directly to the epicardium of the beating heart during open-chest surgery at 15 min after administration of a photosensitizer, talaporfin sodium. We evaluated the lesion size (depth and width) using hematoxylin-eosin staining under varying conditions as follows: laser output (5, 10, 20 W/cm(2)), irradiation time (0-60 s), photosensitizer concentration (0, 2.5, 5 mg/kg), blood oxygen concentration (103.5 +/- 2.1 vs. 548.0 +/- 18.4 torr), and contact force applied during irradiations (low: &lt;20 g, high: &gt;20 g). A laser irradiation at 20 W/cm(2) for 60 s under 5 mu g/kg (29 mu g/mL) of photosensitizer induced a lesion 8.7 +/- 0.8 mm deep and 5.2 +/- 0.2 mm wide. The lesion size was thus positively correlated to the laser power, irradiation time, and photosensitizer concentration, and was independent of the applied contact force and oxygen concentration. In addition, the concentration of the photosensitizer strongly correlated with the changes in the pulse oximetry data and fluorescence of the backscattering laser, suggesting that a clinically appropriate condition could be estimated in real time.
Conclusion Photodynamic therapy-mediated cardiac lesions might be controllable by regulating the photosensitizer concentration, laser output, and irradiation time.

DOI： 10.1093/europace/euu335

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DOI： 10.1093/europace/euv029

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Background: The mechanism underlying the associations of sleep-disordered breathing (SDB) with stroke and atrial fibrillation (AF) is not well established. We explored the relationship between nocturnal intermittent hypoxia, a marker of SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients.
Methods: We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 +/- 9.4 years; body mass index [BMI], 24.8 +/- 3.2; Congestive Heart Failure, Hypertension, Age (&gt;= 75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA(2)DS(2)-VASc) score, 1.2 +/- 1.1, paroxysmal AF, n = 83) using nocturnal pulse oximetry, a noninvasive screening method for nocturnal intermittent hypoxia. Based on 3% oxygen desaturation index (3% ODI), patients were divided into nocturnal intermittent hypoxia (3% ODI &gt; 15; n = 32) and control groups (3% ODI &lt;= 15; n = 102).
Results: The nocturnal intermittent hypoxia group demonstrated significantly higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS(2)) and CHA(2)DS(2)-VASc scores, serum hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and prevalence of hypertension, vascular disease, and sick sinus syndrome. Echocardiographically, nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple regression analysis adjusted for type of AF, CHA(2)DS(2)-VASc score, BMI, plasma brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed that 3% ODI was a factor independently associated with LAA flow velocity (beta = -0.184; 95% confidence interval, -0.818 to -0.006).
Conclusions: Nocturnal intermittent hypoxia was an independent determinant for low LAA flow velocity in patients with AF, suggesting that the connection between SDB and LAA function might underlie the association of AF with stroke.

DOI： 10.1016/j.cjca.2014.12.032

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.

DOI： 10.1161/CIRCRESAHA.116.304679

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Aims The left atrial appendage (LAA) represents the major source of cardiac thrombus formation in patients with atrial fibrillation (AF). Phased-array intracardiac echocardiography (ICE) has become available and frequently used during catheter ablation of AF. We attempted to study the feasibility of using ICE for the visualization and evaluation of the LAA from the pulmonary artery (PA) in patients with AF.
Methods and Results Eighty patients with AF undergoing catheter ablation (70 males, 57.5 +/- 9.1 years) were included. Transoesophageal echocardiography was performed on the prior day before the catheter ablation, and ICE was performed just before the transseptal puncture during the catheter ablation. The ICE catheter was advanced up into the PA from the femoral vein, where the LAA was clearly and entirely visualized by manipulating the ICE catheter. We compared the degree of spontaneous echo contrast, and the correlationwas obtained between the ICE and TEE (kappa = 0.534, P &lt; 0.001). Furthermore, the LAA flow velocity (LAA emptying and filling velocities) measured by ICE had a good correlation to that measured by TEE (R = 0.872, P &lt; 0.01 and R = 0.753, P &lt; 0.01, respectively). No patients developed any complications.
Conclusion The utilization of ICE in the PA is feasible for the observation and evaluation of the LAA.

DOI： 10.1093/europace/euu383

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BACKGROUND 3 waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood.
OBJECTIVE The purpose of this study was to examine the 3-wave dynamicity in a general patient population.
METHODS The responses of 3 waves (&gt;0.1 mV above the isoelectric line in 2 contiguous Leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The 3-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals.
RESULTS Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 +/- 0.06 mV at the baseline RR interval of 853 +/- 152 ms, 0.25 +/- 0.11 mV at the RR interval in the conducted APB of 545 +/- 133 ms (P = .0018), and 0.19 +/- 0.08 mV at the RR interval of 1146 +/- 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 +/- 0.12 mV vs 0.42 +/- 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (&gt;0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality.
CONCLUSION 3 waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this.

DOI： 10.1016/j.hrthm.2014.11.010

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DOI： 10.1016/j.ijcard.2014.10.157

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There exist circadian patterns in the occurrence of sudden cardiac death. The suprachiasmatic nuclei is the 'master clock' in mammalian bodies. Furthermore, several circadian genes have been successfully isolated in basic studies and a huge variety of key players form the human circadian rhythm. Obvious circadian patterns are present in the occurrence of critical events, but those characteristics differ greatly according to each disease. In this review we summarized the current understanding of the basic mechanism and association with specific cardiovascular diseases that demonstrate a circadian onset of fatal events. We also summarized the recent deep understanding of sleep-disordered breathing. The close relationship between sleep-disordered breathing and cardiovascular diseases may provide us with the possibility of a novel intervention against sudden cardiac death.

DOI： 10.2174/1381612821666150706104857

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

Aims Accumulating data show the efficacy of catheter ablation (CA) for atrial fibrillation (AF)
however, postoperative recurrence is not uncommon. The aim of this study was to identify predictors of AF recurrence in patients undergoing CA. Methods and results We studied 100 patients with symptomatic paroxysmal (68) or persistent (32)AFwhounderwentCApreceded by transthoracic echocardiographic examination. Of these, 50 had sinus rhythm during echocardiography (Group NSR) and 50 had AF rhythm (Group AF). The left atrial (LA) strain was measured by two-dimensional speckle tracking echocardiography. Echocardiographic parameters were compared between the patients with AF recurrence and no recurrence. During 12 months of follow-up, 26 of 100 patients (11 in Group NSR and 15 in Group AF) had AF recurrence
these patients had significantly longer AF duration, a lower LA global strain (LA-GS), lower LA lateral total strain (LA-LS), and larger maximumLAvolume index (LAVImax) than thosewhomaintained sinus rhythm. Multivariate logistic regression identified basal LA-LS and LAVImax as independent predictors of AF recurrence. Furthermore, receiver operating characteristic analyses revealed that basal LA-LS was the most useful parameter for predicting AF recurrence [area under the curve (AUC): 0.84 vs. 0.74 in LAVImax]. Subanalyses showed that LAVImax was another independent predictor of AF recurrence in Group AF, but not in Group NSR, while basal LA-LS was a significant predictor in both groups. Conclusion LA myocardial function assessed by basal LA-LS could predict AF recurrence after CA. Notably, such an assessment could be applicable even during AF rhythm, suggesting its convenience in the clinical setting without defibrillation before analysis.

DOI： 10.1093/ehjci/jev028

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Background-Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model.
Methods and Results-We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously.
Conclusions-Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.

DOI： 10.1161/CIRCINTERVENTIONS.114.001610

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Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of similar to 2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 x 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNPrs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 x 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role ofsodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.

DOI： 10.1093/hmg/ddu375

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Background-Electrical storms (ESs) in patients with Brugada syndrome (BrS) are rare though potentially lethal.
Methods and Results-We studied 22 men with BrS and ES, defined as &gt;= 3 episodes/d of ventricular fibrillation (VF) and compared their characteristics with those of 110 age-matched, control men with BrS without ES. BrS was diagnosed by a spontaneous or drug-induced type 1 pattern on the ECG in the absence of structural heart disease. Early repolarization (ER) was diagnosed by J waves, ie, &gt;0.1 mV notches or slurs of the terminal portion of the QRS complex. The BrS ECG pattern was provoked with pilsicainide. A spontaneous type I ECG pattern, J waves, and horizontal/descending ST elevation were found, respectively, in 77%, 36%, and 88% of patients with ES, versus 28% (P&lt;0.0001), 9% (P=0.003), and 60% (P=0.06) of controls. The J-wave amplitude was significantly higher in patients with than without ES (P=0.03). VF occurred during undisturbed sinus rhythm in 14 of 19 patients (74%), and ES were controlled by isoproterenol administration. All patients with ES received an implantable cardioverter defibrillator and over a 6.0 +/- 5.4 years follow-up, the prognosis of patients with ES was significantly worse than that of patients without ES. Bepridil was effective in preventing VF in 6 patients.
Conclusions-A high prevalence of ER was found in a subgroup of patients with BrS associated with ES. ES appeared to be suppressed by isoproterenol or quinidine, whereas bepridil and quinidine were effective in the long-term prevention of VF in the highest-risk patients.

DOI： 10.1161/CIRCEP.114.001806

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BACKGROUND The circadian pattern of ventricular fibrillation (VF) episodes in patients with idiopathic ventricular fibrillation (IVF) is poorly understood. OBJECTIVE The purpose of this study was to assess the circadian pattern of VF occurrence in patients with IVF.
METHODS Excluding Brugada syndrome and other primary electrical diseases, the circadian pattern of VF occurrence was determined in 64 patients with IVF. The clinical and electrocardiographic characteristics were compared among patients with nocturnal (midnight to 6:00 AM) VF and nonnocturnal VF in relation to 3 waves. A 3 wave was defined as either notching or a slur at the QRS terminal &gt;0.1 mV above the isoelectric line in contiguous leads.
RESULTS The overall distribution pattern of VF occurrence showed 2 peaks at approximately 6:00 AM and around 8:00 PM, Nocturnal VF was observed in 20 patients (31.3%), and J waves were present in 14 of these 20 individuals (70.0%), whereas 3 waves were less frequent in the 44 nonnocturnal patients with VF: 16 (36.4%) (P = .0117). Among patients with J waves, nocturnal VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was Less common in patients without 3 waves, occurring in only 17.6% (P = .0124). Both the type and Location of J waves and the pattern of the ST segment were similar between the nocturnal and nonnocturnal VF groups. 3 waves were associated with a VF storm and Long-term arrhythmia recurrence.
CONCLUSION In IVF, the presence of J waves may characterize a higher nocturnal incidence of VF and a higher acute and chronic risk of recurrence.

DOI： 10.1016/j.hrthm.2014.08.022

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Background: We performed contact force (CF) monitoring during pulmonary vein (PV) isolation to evaluate CF according to sheath type, catheter position, and inadequate ablation.
Methods: Thirty consecutive patients (paroxysmal atrial fibrillation, 23; CHADS(2) score, 0.5 +/- 0.7; age, 56 +/- 10 years) who underwent PV isolation using a CF-sensing catheter were included. Data for operator-blinded CF, impedance, and duration of the "first touch" (first round of ablation in each PV) was collected. We compared the CF, maximum CF, force-time integral, average impedance, and impedance drop (Delta impedance) between different sheaths (Swartz(TM) vs. Agilis(TM) in 12 different catheter positions, and in inadequate first touches requiring additional ablation.
Results: A total of 1283 ablation points (Swartz(TM), 620 points; Agilis(TM), 663 points) were evaluated. The average CF was significantly higher in the Agilis(TM) group (17.8 +/- 13.0 g) than the Swartz(TM) group (15.0 +/- 12.4 g; P &lt; 0.001), especially in the anterior, inferior-anterior, and inferior-posterior sections of the right PV, and the top of the roof, and calina of the left PV. The Delta impedance showed a mildly significant negative relationship with the average CF (r = -0.206; P &lt; 0.001) and with the force-time integral (r = -0.279; P &lt; 0.001). Compared to first touches, the average CF and Delta impedance were significantly smaller in inadequate first touches in the Swartz(TM) group, but not in the Agilis(TM) group.
Conclusions: CF for PV isolation was significantly different depending on the position of the catheter and the type of sheath. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2014.09.189

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Ras-related small G-protein Rad plays a critical role in generating arrhythmias via regulation of the L-type Ca2+ channel (LTCC). The aim was to demonstrate the role of Rad in intracellular calcium homeostasis by cardiac-Specific dominant-negative suppression of Rad. Transgenic (TG) mice overexpressing dominantnegative mutant Rad (S105N Rad TG) were generated. To measure intracellular Ca2+ concentration ([Ca2+](i)), we recorded [Ca2+](i) transients and Ca2+ sparks from isolated cardiomyocytes using confocal microscopy. The mean [Ca2+](i) transient amplitude was significantly increased in S105N Rad TG cardiomyocytes, compared with control littermate mouse cells. The frequency of Ca2+ sparks was also significantly higher in TG cells than in control cells, although there were no significant differences in amplitude. The sarcoplasmic reticulum Ca2+ content was not altered in the S105N Rad TG cells, as assessed by measuring caffeine-induced [Ca2+](i) transient. In contrast, phosphorylation of Ser(2809) on the cardiac ryanodine receptor (RyR2) was significantly enhanced in TG mouse hearts compared with controls. Additionally, the Rad-mediated RyR2 phosphorylation was regulated via a direct interaction of Rad with protein kinase A (PKA). (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2014.08.126

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Background: Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.
Methods and Results: Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR-0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.156x(1-RR) for Fukuda Denshi and QTc = QT+0.152x(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was similar to 10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.
Conclusions: We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.

DOI： 10.1371/journal.pone.0106947

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DOI： 10.1016/j.ijcard.2014.04.159

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Background We investigated various serum inflammatory markers to predict ablation responders who have no atrial fibrillation (AF) relapse after the initial ablation.
Methods Forty-four consecutive AF patients (age: 59 +/- 8 years, paroxysmal: 31, CHADS(2): 1.1 +/- 1.1) who underwent an initial pulmonary vein isolation were investigated. Various serum inflammatory markers, such as adiponectin, ANP, BNP, 1CTP, F1+2, hs-CRP, IL-6, intact P1NP, MDA-LDL, MMP-2, TGF-beta, TIMP-2, and TNF-alpha, were evaluated prior to ablation. AF relapse was defined as AF documented in telemonitoring electrocardiograms twice a day during 9.7 +/- 2.4 months of follow-up with three months of a blanking-period.
Results A total of 29 patients (paroxysmal: 21) maintained sinus rhythm after the initial catheter ablation. These ablation responders had significantly lower MMP-2 (Sinus vs. Relapsed: 748 +/- 132.7 vs. 841.2 +/- 152.4 ng/mL, P=0.042) and TNF-alpha (1.1 +/- 0.4 vs. 1.8 +/- 1.7 pg/mL, P=0.046) levels prior to ablation. A BNP-adjusted Cox multivariate regression analysis revealed that the independent predictive factor for AF recurrence was high MMP-2 levels (&gt;766 ng/mL) accompanied by high TNF-a levels (&gt;1.2 pg/mL).
Conclusions The levels of MMP-2 and TNF-a might be useful for predicting initial AF catheter ablation responders.

DOI： 10.1016/j.hlc.2014.02.003

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DOI： 10.1016/j.ijcard.2014.04.032

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DOI： 10.1016/j.cjca.2014.01.008

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DOI： 10.1016/j.ijcard.2014.01.067

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DOI： 10.1007/s00059-013-3784-4

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A 79 year-old male without structural heart disease suffered from drug refractory ventricular tachycardia (VT). VTs and premature ventricular complexes (PVCs) with the same morphology occurred incessantly with a concordant R pattern in chest leads and a tall R in Lead II, III, and aVF. The origin was expected to be near the left epicardial ventricular outflow tract (LVOT), which was termed the left ventricular summit area. Pace-mapping from the LVOT and the left coronary cusp (LCC) did not match well with the QRS morphology of the PVC. A good match was obtained from the distal great cardiac vein (GCV), and radiofrequency (RF) delivery eliminated the PVC and VT. However, the PVC recurred four times upon cessation of RF delivery. By placing an ablation catheter at the LCC, we obtained pace-mapping showing two different types of QRS morphologies; one was an rS pattern in V1, and the other was an R pattern in V1 with a longer stimulus to QRS interval, which was a nearly perfect match to the PVC. RF application to the LCC permanently eliminated PVCs and VTs. Several VTs from the epicardial LVOT can be cured by RF application from both the distal GCV and the LCC.

DOI： 10.1016/j.hlc.2013.04.124

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Electrophysiological Properties of the Superior Vena Cava and Venoatrial Junction Background Although the superior vena cava (SVC) has been well known to be one of the important foci triggering atrial fibrillation (AF), its electrophysiological characteristics have received little research attention. The aim of this study was to investigate the electrophysiological properties of the SVC and venoatrial junction (VAJ). Methods Twenty-five consecutive AF patients without structural heart disease undergoing electrical SVC isolation were included in this study. After pulmonary vein isolation, a circular decapolar catheter and 2 multipolar catheters were emplaced in the VAJ, right atrial appendage (RAA), and SVC, respectively. Burst pacing and single extrastimulus were applied from the RAA and SVC. The atrial and caval potentials on the circular catheter in the VAJ were investigated. Results Intracaval conduction delay and various degrees of conduction block over the VAJ were observed with burst pacing from both the RAA and SVC. A single extrastimulus from the RAA and SVC with a basic cycle length of 600 milliseconds prolonged the conduction time via the VAJ by 81 +/- 49.7 milliseconds and 61 +/- 58.7 milliseconds, respectively. The atrial and caval electrograms at the VAJ, which were separated from each other by pacing applications, facilitated mapping of the earliest activation site at the VAJ. Conclusions Intracaval conduction delay and decremental conduction property via the VAJ were demonstrated using pacing maneuvers. Pacing applications from the RAA or SVC can help distinguish the atrial and caval potentials and can facilitate mapping of the optimal ablation sites to isolate the SVC.

DOI： 10.1111/jce.12271

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DOI： 10.1111/jce.12281

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Electrophysiological Properties of the Superior Vena Cava and Venoatrial Junction Background Although the superior vena cava (SVC) has been well known to be one of the important foci triggering atrial fibrillation (AF), its electrophysiological characteristics have received little research attention. The aim of this study was to investigate the electrophysiological properties of the SVC and venoatrial junction (VAJ). Methods Twenty-five consecutive AF patients without structural heart disease undergoing electrical SVC isolation were included in this study. After pulmonary vein isolation, a circular decapolar catheter and 2 multipolar catheters were emplaced in the VAJ, right atrial appendage (RAA), and SVC, respectively. Burst pacing and single extrastimulus were applied from the RAA and SVC. The atrial and caval potentials on the circular catheter in the VAJ were investigated. Results Intracaval conduction delay and various degrees of conduction block over the VAJ were observed with burst pacing from both the RAA and SVC. A single extrastimulus from the RAA and SVC with a basic cycle length of 600 milliseconds prolonged the conduction time via the VAJ by 81 ± 49.7 milliseconds and 61 ± 58.7 milliseconds, respectively. The atrial and caval electrograms at the VAJ, which were separated from each other by pacing applications, facilitated mapping of the earliest activation site at the VAJ. Conclusions Intracaval conduction delay and decremental conduction property via the VAJ were demonstrated using pacing maneuvers. Pacing applications from the RAA or SVC can help distinguish the atrial and caval potentials and can facilitate mapping of the optimal ablation sites to isolate the SVC. © 2014 Wiley Periodicals, Inc.

DOI： 10.1111/jce.12271

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DOI： 10.1016/j.ijcard.2013.03.182

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DOI： 10.1016/j.ijcard.2013.07.187

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We present a patient with ventricular fibrillation (VF) associated with J-wave manifestation following pericarditis after catheter ablation of paroxysmal atrial fibrillation (AF). The premature ventricular contraction induced VF with J-waves in the inferior leads 2 days after the procedure. The patient's juvenile onset of AF and a family history of sudden cardiac death strongly suggested an underlying hereditable channelopathy. The late gadolinium enhancement in the posterior wall, viewed by cardiac magnetic resonance imaging, matched the leads of the J-waves. VF might develop in juvenile onset of AF especially in individuals with a family history of sudden cardiac death. © 2013 Canadian Cardiovascular Society.

DOI： 10.1016/j.cjca.2013.05.006

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DOI： 10.1093/europace/eut219

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Objectives This study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms. Background Some IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known. Methods Ninety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves &gt
0.1 mV above the isoelectric line in contiguous leads. Results Fourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p &lt
0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs. Conclusions The VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.

DOI： 10.1016/j.jacc.2013.05.030

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Background
The characteristic ECG of Brugada syndrome (BS) can be masked by complete right bundle-branch block (CRBBB) and exposed by resolution of the block or pharmacological or pacing maneuvers.
Methods and Results
The study consisted of 11 patients who had BS and CRBBB. BS was diagnosed before the development of CRBBB, on the resolution of CRBBB, or from new characteristic ST-segment changes that could be attributable to BS. Structural heart diseases were excluded, and coronary spasm was excluded on the basis of a provocation test at catheterization. In 7 patients, BS was diagnosed before the development of CRBBB. BS was diagnosed when CRBBB resolved spontaneously (n=1) or by right ventricular pacing (n=3). The precipitating cause for the spontaneous resolution of CRBBB, however, was not apparent. On repeated ECGs, new additional upward-convex ST-segment elevation was found in V-2 or V-3 in 3 patients. In 2 patients, new ST-segment elevation was induced by class I-C drugs. The QRS duration was more prolonged in patients with BS and CRBBB compared with age- and sex-matched controls: 170 +/- 13 versus 145 +/- 15 milliseconds in V-1 and 144 +/- 19 versus 128 +/- 7 milliseconds in V-5 (both P&lt;0.0001). The amplitude of R in V-1 was larger in the BS patients than in the control subjects (P=0.0323), but that of R was similar (P=0.0560).
Conclusions
BS can coexist behind CRBBB, and CRBBB can completely mask BS. BS might be demonstrated by relief of CRBBB or by spontaneous or drug-induced ST-segment elevation. The prevalence, mechanism, and clinical significance of a combination of CRBBB and BS are yet to be determined.

DOI： 10.1161/CIRCULATIONAHA.113.003472

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BACKGROUND A substantial number of patients with idiopathic ventricular fibrillation (IVF) present with no specific electrocardiographic (ECG) findings.
OBJECTIVE To evaluate complete right bundle branch block (RBBB) in patients with IVF.
METHODS Patients with IVF showing complete RBBB were included in the present study. Structural and primary electrical diseases were excluded, and provocation tests were performed to exclude the presence of spastic angina or Brugada syndrome (BrS). The prevalence of complete RBBB and the clinical and ECG parameters were compared either in patients with IVF who did not show RBBB or in the general population and age and sex comparable controls with RBBB.
RESULTS Of 96 patients with IVF, 9 patients were excluded for the presence of BrS. Of 87 patients studied, 10 (11.5%) patients showed complete RBBB. None had structural heart diseases, BrS, or coronary spasms. The mean age was 44 +/- 15 years, and 8 of 10 patients were men. Among the ECG parameters, only the QRS duration was different from that of the other patients with IVF who did not show complete RBBB. Ventricular fibrillation recurred in 3:2 in the form of storms, which were well suppressed by isoproterenol. Complete RBBB was found less often in control subjects (1.37%; P &lt;.0001), and the QRS duration was more prolonged in patients with IVF: 139 +/- 10 ms vs 150 +/- 14 ms (P = .0061).
CONCLUSIONS Complete RBBB exists more often in patients with IVF than in controls. A prolonged (IRS complex suggests a conduction abnormality. Our findings warrant further investigation of the role of RBBB in the development of arrhythmias in patients with IVF.

DOI： 10.1016/j.hrthm.2013.03.013

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AimsPhrenic nerves (PNs) can be damaged during interventional cardiovascular therapy because of the nerves' proximity to the heart. This study aimed to analyse the anatomy of the PN by performing three-dimensional (3-D) imaging and pace mapping.Methods and resultsForty consecutive patients with atrial fibrillation referred for catheter ablation were enrolled in this study and underwent preoperative cardiovascular computed tomography (CT). In 10 patients with sinus rhythm during tomography, 3-D images of the right and left pericardiophrenic bundles (PBs), consisting of the ipsilateral PN and accompanying vessels, were reconstructed from the CT data. During the electrophysiological study, PN pace mapping was performed from both atria. The course of the PBs generated by CT imaging and the PN pace map generated by the 3-D mapping system were compared. By electrical pacing, the PNs were captured in 40 individuals (100%) from the superior vena cava and the right atrium, and in 17 patients (43%) from the left atrial appendage. Clear 3-D images of PBs were reconstructed in all cases in which CT-reconstruction was performed. The distance between the locations of the right PB generated by CT imaging and those of the right PN-capture sites in the right-sided heart on the mapping system was 8.7 ± 5.8 mm.ConclusionsThe 3-D routes of the bilateral PNs passing near the heart were verified by pace mapping. The preoperatively reconstructed 3-D course of the PB succeeded in locating the PN, which may facilitate the comprehension of PN anatomy to avoid its injury during interventional cardiovascular therapy. © 2013 The Author.

DOI： 10.1093/europace/eus439

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Ridge-Related Reentry Introduction The ridge between the left pulmonary veins (PV) and the left atrial appendage composes part of the lateral mitral isthmus (LMI). Following circumferential PV isolation and LMI linear ablation for the treatment of atrial fibrillation (AF), a critical pathway might develop over the ridge leading to a ridge-related reentry (RRR).
Methods and Results Out of 61 patients who underwent circumferential PV isolation appended by LMI ablation, 5 patients developed RRR. The diagnosis of RRR was based on (1) macro-reentrant atrial tachycardia involving the septum, anterior and inferior wall of the left atrium; (2) slow conduction along the ridge; (3) wide-split double potentials in the ventricular aspect of the LMI were identified with the coronary sinus (CS) electrodes. RRR was investigated with electroanatomical mapping and entrainment mapping and catheter ablation was carried out in all patients. The mean cycle length (CL) of RRR was 312 +/- 82 milliseconds and the PPIs at the left atrial septum, inferior and anterior wall during RRR were 10 +/- 6, 12 +/- 8, 9 +/- 5 milliseconds longer than the RRR CL. The interval of the double potentials recorded in the CS electrodes crossing the LMI was 164 +/- 38 milliseconds during RRR and the PPI on the LMI near the mitral annulus was 57 +/- 10 milliseconds longer than the RRR CL. Catheter ablation was performed anatomically by targeting the ridge and successfully terminated RRR.
Conclusion After circumferential PV isolation and ablation for LMI in patients with AF, RRR can develop by utilizing the surviving myocardial tissue of the ridge as a critical pathway.

DOI： 10.1111/jce.12120

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BACKGROUND&lt;bold&gt; &lt;/bold&gt;Strokes develop even in patients with low CHADS(2) scores, and the left atrial appendage (LAA) is the embolic source 90% of the time. We focused on the LAA morphology as a new predictor of strokes. &lt;bold&gt; &lt;/bold&gt;OBJECTIVE&lt;bold&gt; &lt;/bold&gt;To clarify the anatomical characteristics of the LAA for risk stratification of strokes in patients with nonvalvular atrial fibrillation (AF) who have low CHADS(2) scores. &lt;bold&gt; &lt;/bold&gt;METHODS&lt;bold&gt; &lt;/bold&gt;Among 80 patients who underwent catheter ablation of AF with contrast-enhanced computed tomography, the LAA characteristics were compared between 30 patients with histories of strokes and 50 age-matched controls. The LAA anatomy was classified into 4 types-"cactus," "cauliflower," "chicken wing," and "windsock"-discriminated by the computed tomography measurements of the length, angle, and number of lobes of the LAA. &lt;bold&gt; &lt;/bold&gt;RESULTS&lt;bold&gt; &lt;/bold&gt;The average CHADS2 score did not differ significantly between patients with stroke and controls (0.8 +/- 0.8 vs 0.6 +/- 0.7; P = .277). Eight (26.7%) patients with stroke had CHA(2)DS(2)-VASc scores of 0. The left atrial size, LAA flow velocity, left ventricular function, and serum brain natriuretic peptide level were also unable to predict strokes. However, a "cauliflower" LAA, defined as a main lobe of less than 4 cm long without forked lobes, was significantly more common in patients with stroke (odds ratio 3.857; 95% confidence interval 1.482-10.037; P = .005). The CHA(2)DS(2)-VASc score-adjusted logistic regression analysis revealed the cauliflower LAA as an independent predictor of a stroke (odds ratio 3.355; 95% confidence interval 1.243-9.055; P = .017). &lt;bold&gt; &lt;/bold&gt;CONCLUSIONS&lt;bold&gt; &lt;/bold&gt;The LAA anatomy might be useful for predicting strokes in patients with nonvalvular AF who have low CHADS2 scores.

DOI： 10.1016/j.hrthm.2013.01.036

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DOI： 10.1007/s00059-012-3666-1

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A 45-year-old male was admitted to our hospital after successful resuscitation of cardiac arrest. Ventricular fibrillation (VF) had occurred during breakfast and was defibrillated by an automated external defibrillator operated by emergency medical service staff. On admission, his ECG demonstrated complete right bundle branch block as the sole abnormality. Intensive examination could not detect any structural disease leading to a diagnosis of idiopathic VF and implantation of an ICD. VF storm occurred one month after hospital discharge and beta-blocker, amiodarone, and sedative administration had no effect on VF. Likewise, catheter ablation for triggering premature ventricular beats failed to control the VF storm. The VF storm then subsided in the following weeks and the patient was discharged on amiodarone. A half month later VF storm recurred and the patient was admitted again. This time, isoproterenol infusion was effective in suppressing VF, and thereafter the patient was administered bepridil and followed up without recurrence of VF for 1.5 years. From these beneficial effects, the VF of the patient was suggested to share common arrhythmogenic characteristics to those of Brugada syndrome or J-wave associated VF.

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Background: Phrenic nerve (PN) injury is a potential complication that can occur during superior vena cava (SVC) isolation to cure atrial fibrillation (AF). Avoiding radiofrequency (RF) energy delivery is the safer alternative but may result in failed isolation. High-output PN pacing above the ablation site (upstream PN pacing) to confirm whether the PN is intact is a promising technique to avoid PN injury. This study was conducted to elucidate the safety of delivering RF energy at the site of capture of the right PN using upstream high-output pacing during electrical SVC isolation. Methods: SVC isolation was conducted in 41 drug-resistant AF patients. When high-output pacing (25 mA) from the distal tip of the ablation catheter captured the PN at the right atrial-SVC junction, upstream PN pacing (cycle length: 10001500 ms) was applied during RF delivery. The application of RF energy was stopped upon the failure or weakness of diaphragmatic twitching. The feasibility of SVC isolation using upstream PN pacing was investigated. Results: In all 41 patients, SVC isolation was successfully achieved. RF energy was delivered at the PN capture site in 26 patients (154 +/- 138 second, 18 +/- 5 W), and upstream PN pacing was successfully applied in all of the patients. Out of 46 SVC isolations, including five repeated sessions, PN injury occurred in one patient, who recovered spontaneously within 2 weeks. Conclusions: Upstream PN pacing may be effective for the safe completion of SVC isolation and to reduce the severity of PN injury. (PACE 2012; 35:10531060)

DOI： 10.1111/j.1540-8159.2012.03465.x

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DOI： 10.1161/CIRCULATIONAHA.112.097527

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Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs).
We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells.
This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine.

DOI： 10.1093/cvr/cvs206

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DOI： 10.1016/j.ijcard.2011.11.008

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Objectives This study evaluated the pause-dependency of the J-wave to characterize this phenomenon in idiopathic ventricular fibrillation (VF).
Background The J-wave can be found in apparently healthy subjects and in patients at risk for sudden cardiac death, and risk stratification is therefore needed.
Methods Forty patients with J-wave-associated idiopathic VF were studied for J waves with special reference concerning pause-dependent augmentation. J waves were defined as those &gt;= 0.1 mV above the isoelectric line and were compared with 76 non-VF patients of comparable age and sex.
Results The J-wave was larger in patients with idiopathic VF than in the controls: 0.360 +/- 0.181 mV versus 0.192 +/- 0.064 mV (p = 0.0011). J waves were augmented during storms of VF (n +/- 9 [22.5%]), which was controlled by isoproterenol; they disappeared within weeks in 5 patients. In addition, sudden prolongation of the R-R interval was observed in 27 patients induced by benign arrhythmia, and 15 patients (55.6%) demonstrated pausedependent augmentation (from 0.391 +/- 0.126 mV to 0.549 +/- 0.220 mV; p +/- 0.0001). In the other 12 experimental subjects and in the 76 control subjects, J waves remained unchanged. Pause-dependent augmentation of J waves was detected in 55.6% (sensitivity) but was specific (100%) in the patients with idiopathic VF with high positive (100%) and negative (86.4%) predictive values.
Conclusions Pause-dependent augmentation of J waves was confirmed in about one-half of the patients with idiopathic VF after sudden R-R prolongation. Such dynamicity of J waves was specific to idiopathic VF and may be used for risk stratification. (J Am Coll Cardiol 2012; 59: 1948-53) c 2012 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2012.02.028

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

During therapeutic hypothermia, QT interval is prolonged. In patients with congenital long QT syndrome (LQTs), a longer QT interval was associated with significantly increased risk of cardiac arrest (CA). Therefore, therapeutic hypothermia may have proarrhythmic effects in survivors of CA due to congenital LQTs. A 27-year-old man was resuscitated from CA due to congenital LQTs type 3 and Brugada syndrome. Torsade de pointes (TdP) recurred spontaneously on admission (body temperature, 36.9 degrees C). During mild hypothermia therapy, QTc increased from 499 (36.9 degrees C) to 667 milliseconds (33.8 degrees C), although TdP was not induced. A 13-year-old boy with congenital LQTs type 1 underwent therapeutic hypothermia after resuscitation. Short-acting beta-blocker was administered intravenously during this treatment. The QTc increased from 534 (36.4 degrees C) to 626 milliseconds (34.3 degrees C). However, TdP did not recur during mild hypothermia therapy. In both patients, electrolyte abnormalities were checked frequently and corrected immediately. QT prolongation remained a couple of days after completion of rewarming. The withdrawal of sedative drugs and extubation were not pursued before QT shortening reached to a plateau. Both patients were fully recovered from neurologic damage. During therapeutic hypothermia, QT interval was extremely prolonged, although TdP did not recur in 2 patients with congenital LQTs. Therapeutic hypothermia may be beneficial for comatose survivors of CA due to LQTs.

DOI： 10.1016/j.ajem.2011.02.019

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

Background and Purpose: Some de- and re-polarization patterns can reflect an increased risk of ventricular tachyarrhythmias. We studied whether some electrocardiographic (ECG) patterns are able to predict the development of ventricular fibrillation (VF) during acute myocardial infarction (MI).
Methods: We compared the patterns of ST-T segment of 78 patients who developed VF during acute MI (patient with VF) vs 170 comparable patients with acute MI but with no VF complications.
Results: Of the VF group, 47 developed out-of-hospital VF and 31 developed VF after their admission to the hospital. A steep downsloping ST segment toward a negative T wave with or without a short, flat, or rising portion at the initial portion was observed in 69.2% of the 78 patients: 61.3% in patients with pre-VF and 74.5% in patients with post-VF, vs 9.4% of patients who did not develop VF (P &lt; .0001). In 90.6% of the latter, a typical upward-concave or convex "ischemic" pattern of the ST segment was observed. Thus, the characteristic ST-T patterns were highly associated with VF with a specificity greater than 90%.
Conclusions: A steep downsloping ST segment may characterize the ECGs of patients who develop VF during acute MI. (c) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jelectrocard.2011.11.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：URBAN & VOGEL  

A 58-year-old male was referred for catheter ablation for atrial fibrillation. He was incidentally diagnosed with cor triatriatum sinister by preoperative transesophageal echocardiography and cardiovascular computed tomography. The patient has since been free from atrial fibrillation for over 24 months following successful electrical pulmonary vein isolation. The rapidly soaring number of cases undergoing catheter ablation for atrial fibrillation and imaging investigation prior to the procedure may increase the incidental detection of asymptomatic congenital heart diseases.

DOI： 10.1007/s00059-011-3492-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: Hypertrophic cardiomyopathy (HCM), which is inherited as an autosomal dominant trait, is the most prevalent hereditary cardiac disease. Although there are several reports on the systematic screening of mutations in the disease-causing genes in European and American populations, only limited information is available for Asian populations, including Japanese.
Methods and Results: Genetic screening of disease-associated mutations in 8 genes for sarcomeric proteins, MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TPM1, and ACTC, was performed by direct sequencing in 112 unrelated Japanese proband patients with familial HCM; 37 different mutations, including 13 novel ones in 5 genes, MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, were identified in 49 (43.8%) patients. Among them, 3 carried compound heterozygous mutations in MYBPC3 or TNNT2. The frequency of patients carrying the MYBPC3, MYH7, and TNNT2 mutations were 19.6%, 10.7%, and 8.9%, respectively, and the most frequently affected genes in the northeastern and southwestern parts of Japan were MYBPC3 and MYH7, respectively. Several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations.
Conclusions: This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan. (Circ J 2012; 76: 453-461)

DOI： 10.1253/circj.CJ-11-0876

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Language：Japanese  

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Other Link： http://search.jamas.or.jp/link/ui/2012113161

Language：English   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.50.5354

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The presence of J wave is associated with a risk for the sudden death, and termed J wave syndrome. A 37-year-old male was referred to our hospital for an ICD implant for secondary prevention. He did not have a history of syncope or family history of sudden death but experienced an episode of cardiac arrest during deskwork at midnight. Ambulance was called and bystander CPR was performed by his wife while waiting for the arrival. A record of AED showed successful defibrillation of VF by multiple DC shocks. However, the prominent J wave was apparent post-VF. The J wave was augmented during mild hypothermia therapy after admission to the hospital but persisted during his hospital course. He recovered without any neurological deficit and the rest of his clinical course was uneventful. Intensive examination excluded structural heart diseases and VF was not induced by programmed electrical stimulation during EP study. Furthermore, an intravenous administration of pilsicainide did not disclose coved type ST elevation and signal averaged ECG was negative. He had an ICD implant and had no recurrence during 4-year follow up period. This is an interesting case of J wave syndrome whose J wave remained continuously but augmented during VF storm. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PE3_010

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Purpose: Discriminating the potentials of superior vena cava (SVC) from those of right atrium (RA) at the venoatrial junction is sometimes challenging in patients with atrial fibrillation (AF) during SVC isolation. We aimed to establish a technique to identify clear potentials of SVC and RA at venoatrial junction. Methods: Twenty-five AF patients with SVC ectopy undergoing Catheter ablation were included. After pulmonary vein isolation, a circular decapolar Catheter and two multipolar Catheters were placed in the venoatrial junction, RA appendage and SVC, respectively. Burst pacing and single extrastimulus were applied from both RA appendage and SVC. Intervals of the potentials of RA and SVC on the circular Catheter during pacing maneuvers were measured. Results: Decremental conduction property in both directions between the venoatrial junction was observed with pacing maneuvers. The more decremental property was identified in the direction from RA to SVC than in the inverse direction. Single extrastimulus showed more decremental property than burst pacing either from RA appendage or SVC. Single extrastimulus facilitated identification of the earliest activation site of the venoatrial junction by separating the potentials of RA and SVC. Conclusions: Conduction over venoatrial junction showed decremental property, which facilitates mapping of the optimal ablation sites during electrical SVC isolation. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PE4_016

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Backgrounds: During Catheter ablation for atrial fibrillation (AF), extensive application of radiofrequency energy can lead to clot formation. The external irrigation for the tip electrode might prevent clot formation, which remains to be clarified. Methods and Results: We retrospectively studied the incidence of the clot formation during ablation for AF in our facility using irrigation Catheter, in which irrigation flow rate was set at 17ml/min (=or&lt
30W) or 30ml/min (&gt
30W) and the RF generator would be automatically switched off when the temperature rose to 43degrees Celsius or at the impedance rise. Out of 331 cases who underwent AF ablation using irrigation Catheter, 20 clot formations in 17 cases (15 males, 59±9y) were observed. The activated clotting time was kept over 300sec by intravenous heparin administration during left atrial Catheterization. All of clot formations were found at the proximal edge of irrigation tip electrode, which developed at 32.2±4.0W, 42.8±2.9degrees Celsius accompanied byimpedance rise with 34.6±24.2ohm. Clot formation was likely to occur around the right pulmonary vein (PV) (65%) than around the left PV (20%). No strokes or thromboembolisms were found after ablation in every patient. Conclusions: Clot formation can occur during AF ablation even using open irrigation tip Catheter. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PE4_034

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Background: Strokes can develop in patients with atrial fibrillation (AF) having low CHADs2 score. We aimed to clarify the characteristics of left atrial appendages (LAAs) in non-valvular AF stroke patients with low CHADs2 score. Methods and Results: A total of 333 AF patients (paroxysmal : n=222) who underwent computed tomography (CT) and ablation were examined, out of whom 29 patients(8.7%) had strokes(22 males, 60±9yo, 22 paroxysmal). The average CHADs2 score at the onset of stroke was 0.6±0.6, the size of left atrium was 3.9±0.5cm and the blood flow velocity of LAA was 51 ±22cm/sec. LAA anatomy was classified into 4 types of morphologies: “Cauliflower”, “Windsock”, “Cactus”, and “Chickenwing”, and the distribution was compared with 51 age and sex matched control. Comparing stroke group vs. control group, Cauliflower was 69% vs. 31%, Windsock was 19% vs. 31%, Chickenwing was 4% vs. 22% and Cactus was 4% vs. 31%, respectively. Regarding the position of the LAA, lower position of LAA orifice than the left superior pulmonary veins were more common in stroke patients (stroke vs. control
12 (80%) vs. 16 (31%), respectively. Conclusion: AF patients with low CHADs2 score and strokes had well-lobulated and lower positioned LAA. The anatomy of LAAs might be helpful to identify risks for strokes. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PE4_030

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Introduction: Inappropriate shocks(IAS) were associated with increased risk of mortality and deterioration of QOL in pts with ICD. To investigate the efficacy of remote monitoring systems (RM) for reducing IAS. Methods: We retrospectively reviewed consecutive 202pts who had been implanted ICDs from 2005. Incidence of IAS and device-related problems were reviewed in 101pts under RM (CareLink (n=95)/HomeMonitoring (n=6)) during ≤2yrs and in 101control-pts(C) who underwent conventional scheduled-checks during ≤2yrs after ICD implantation. Results: Age, gender, AF, single-chamber ICD, Fidelis-lead, VF detection rate, treatment with amiodarone and β blockers were not significantly different between RM and C groups, except for idiopathic VF (26vs.18%
p&lt
.05) and LVEF (48vs.42%
p&lt
.05). Kaplan-Meier survival curve revealed significant reduction of IAS under RM compared to C group (p=0.032). A total of 10/15 device-related problems were detected in C/RM groups. Device problems were more often confirmed just after IAS in C than RM group (80vs.27%
p&lt
.01). In RM group, 73% of problems had been managed 2±2 days after data detection and did not cause IAS. Multiple regression analysis showed that RM (OR
0.29, 95%CI
0.110.78, p&lt
.05) and age (OR
0.97, 95%CI
0.94-0.996, p&lt
.05) were independently associated with IAS. Conclusions: Incidence of IAS may be reduced under RM which enables us to detect device-related problems before the delivery of IAS from ICD. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP06_4

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Background: Phrenic nerve (PN) injury is a potential complication during superior vena cava (SVC) isolation to cure atrial fibrillation (AF). Avoiding radiofrequency (RF) energy delivery is safer but may lead to a failed isolation. High-output PN pacing above the ablation site, upstream PN pacing, is a promising technique to avoid PN injury. This study was conducted to elucidate the safety of delivering RF energy at the site where high-output pacing captures PN. Methods and Results: SVC isolation was carried out in 41 drug-resistant AF patients. When high-output pacing (25 mA) from the ablation catheter captured PN, upstream PN pacing (cycle length: 1000-1500msec) was applied during RF delivery. RF energy was ceased upon the failure or weakness of diaphragmatic twitching. The feasibility of SVC isolation using upstream PN pacing was investigated. In all 41 patients, SVC isolation was successfully achieved. RF energy was delivered at the PN capture site in 26 patients (154± 138 sec, 18± 5 W), and upstream PN pacing was successfully applied in all patients. Out of 46 SVC isolations, including 5 redo sessions, PN injury occurred in 2 patients, who recovered spontaneously within 2 weeks. Conclusions: Upstream PN pacing is effective in completing SVC isolation safely and reducing the severity of PN injury. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP40_3

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Experience of radiofrequency catheter ablation (RFCA) in patients with dextrocardia and sinus invertus is limited for its extremely rare incidence. A 21-year-old male with recurrent episodes of supraventricular tachycardia was referred to our hospital for the electrophysiological study (EPS). He had received operation for double outlet right ventricle with ventricular septal defect at his age of 9 months. Twelve lead ECG, echocardiography and computed tomography showed dextrocardia with situs invertus. At EPS, electrode catheters were positioned at the right atrial appendage, His bundle - right ventricular apex and the coronary sinus as completely mirror image. Programmed electrical stimulation induced typical atrioventricular nodal reentrant tachycardia (AVNRT). A 3.5 mm tip sarine-irrigated ablation catheter was required to successful ablation of slow pathway (SP), which was not located at usual Koch's triangle region but at rightward position, and the tachycardia became non-inducible. This suggests SP might have located at the right side of atrial septum, despite completely mirror image. The CARTO-XP (Biosense Webster) was useful for determine the intracardiac orientation. This is a unique case of AVNRT in a patient with mirror-image dextrocardia. We could successfully treated AVNRT by sarine-irrigated RFCA. Exact anatomical evaluation using electro-anatomical mapping is critical in such a case with cardiac anomaly. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PE4_098

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Language：English   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

DOI： 10.1111/j.1540-8167.2009.01636.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: The J-RHYTHM (Japanese Rhythm Management Trial for Atrial Fibrillation) study demonstrated the benefit of rhythm-control compared with rate-control in Japanese patients with paroxysmal atrial fibrillation (AF), according to AF-specific quality of life scores. However, detailed information on prescribed antiarrhythmic agents remains unclear.
Methods and Results: Data for 419 patients enrolled in the rhythm-control arm of J-RHYTHM were analyzed. The primary endpoint was defined as a composite of total mortality, cerebral infarction, embolism, bleeding, heart failure, and physical/psychological disability. The secondary endpoint was recurrence of AF. The clinical outcome according to choice of initial antiarrhythmic agent (AA) was assessed by Kaplan-Meier survival curve, and further adjusted by Cox-regression hazard model. The primary endpoint occurred in 16.9%, 6.7%, 15.8% and 23.3% of patients assigned to class Ia, Ib, Ic and III agents (P=0.359). The rate of AF recurrence was significantly higher in patients taking a class III drug (Ia, Ib, Ic, 111=20.3, 23.3, 29.1, 50.0%; P=0.002). However, after adjustment for other clinical variables, the choice of AA was not associated with recurrence of AF (class I vs III, P=0.15).
Conclusions: The incidence of each endpoint did not differ according to the choice of AA. The class III drugs seemed to lower the sinus rhythm maintenance rate, which might be confounded by other comorbid conditions. (Circ J 2010; 74: 71-76)

DOI： 10.1253/circj.CJ-09-0367

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Rhythm control therapy by sodium channel blockers is widely performed for the treatment of paroxysmal atrial fibrillation. Here, we present a case of acquired Brugada syndrome by pill-in-the-pocket treatment using pilsicainide. It is important that this therapy should be applied only after confirming the drug safety to the patients. © 2010 Aizawa et al, publisher and licensee Dove Medical Press Ltd.

DOI： 10.2147/DHPS.S12491

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Long QT syndrome (LQTS) is a hereditary arrhythmia caused by mutations in genes for cardiac ion channels, including a potassium channel, KvLQT1. Inheritance of LQTS is usually autosomal-dominant, but autosomal-recessive inheritance can be observed in patients with LQTS accompanied by hearing loss. In this study, we investigated the functional alterations caused by KCNQ1 mutations, a deletion (delV595) and a frameshift (P631fs/19), which were identified in compound heterozygous state in two patients with autosomal-recessive LQTS not accompanied by hearing loss. Functional analyses showed that both mutations impaired cell surface expression due to trafficking defects. The mutations severely affected outward potassium currents without apparent dominant negative effects. It was found that delV595 impaired subunit binding, whereas P631fs/19 was retained in endoplasmic reticulum due to the newly added 19-amino acid sequence containing two retention motifs (R(633)GR and R(646)LR). This is the first report of novel mechanisms for trafficking abnormality of cardiac ion channels, providing us new insights into the molecular mechanisms of LQTS.

DOI： 10.1074/jbc.M109.017293

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I(f) channel produced by HCN4 in a computer simulation model and found that the I(f) channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I(f) channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.

DOI： 10.1038/jhg.2008.16

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The effect of the electrical charge or the size of tile amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K+ currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue 1313 K and 1313 E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the Site Was Substituted with the smallest neutral amino acid residue: 1313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. 1313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on tile electrical charge or the size of amino acid residue. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2008.11.076

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Mutation in the Selectivity Filter of the KCNQ1.
Introduction: Slowly activating delayed-rectifier potassium currents in the heart are produced by a complex protein with alpha and beta subunits composed of the potassium voltage-gated channel KQT-like subfamily, member 1 (KCNQ1) and the potassium voltage-gated channel Isk-related family, member 1 (KCNE1), respectively. Mutations in KCNQ1 underlie the most common type of hereditary long QT syndrome (LQTS). Like other potassium channels, KCNQ1 has six transmembrane domains and a highly conserved potassium selectivity filter in the pore helix called "the signature sequence." We aimed to investigate the functional consequences of a newly identified mutation within the signature sequence.
Methods and Results: Potassium channel genomic DNA from a family with clinical evidence of LQTS was amplified by polymerase chain reaction (PCR), and the resulting products were then sequenced. Three family members had a double-point mutation in KCNQ1 at nucleotides 938 (T-to-A) and 939 (C-to-A), resulting in an isoleucine-to-lysine change at amino acid position 313. These patients displayed prolonged QTc intervals (629, 508, and 500 ms(1/2,) respectively) and repetitive episodes of syncope, but no deafness. Three-dimensional structure modeling of KCNQ1 revealed that this mutation is located at the center of the channel pore. COS-7 cells displayed a lack of current when transfected with a plasmid expressing the mutant. In addition, the mutant displayed a dominant negative effect on current but appeared normal with respect to plasma membrane integration.
Conclusion: An I313K mutation within the selectivity filter of KCNQ1 results in a dominant-negative loss of channel function, leading to a long QT interval and subsequent syncope.

DOI： 10.1111/j.1540-8167.2007.01076.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

BACKGROUND Atria( fibrillation (AF) is the most common clinical arrhythmia and a major cause of cardiovascular morbidity and mortality. Among the gene defects previously associated with AF is a gain of function of the slowly activating delayed rectifier potassium current I,,, secondary to mutations in KCNQ1. Coexpression of KCNE5, the gene encoding the MiRP4 P-subunit, has been shown to reduce I-Ks.
OBJECTIVE The purpose of this study was to test the hypothesis that mutations in KCNE5 are associated with AF in a Large cohort of patients with AF.
METHODS One-hundred fifty-eight patients with AF were screened for mutations in the coding region of KCNE5.
RESULTS A missense mutation involving substitution of a phenylalanine for leucine at position 65 (L65F) was identified in one patient. This patient did not have a history of familial AF, and neither KCNQ1 nor KCNE2 mutations were found. Transient transfection of Chinese hamster ovary (CHO) cells expressing I-Ks (KCNQ1+KCNE1) with KCNE5 suppressed the developing and tail currents of I, in a concentration-dependent manner. Transient transfection with KCNE5-L65F failed to suppress I-Ks yielding a current indistinguishable from that recorded in the absence of KCNE5. Developing currents recorded during a test pulse to +60 mV and tail currents recorded upon repolarization to -40 mV both showed a significant concentration-dependent gain of function in I-Ks with expression of KCNE5-L65F vs KCNE5-WT.
CONCLUSION The results of this study suggest that a missense mutation in KCNE5 may be associated with nonfamilial or acquired forms of AF. The arrhythmogenic mechanism most likely is a gain of function of I-Ks.

DOI： 10.1016/j.hrthm.2007.12.019

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Language：English   Publisher：(一社)日本循環器学会  

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DOI： 10.1016/j.jacc.2007.07.037

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Novel Mutation in KCNQ1 as a Cause of LQT1.
Introduction: Long QT Syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and life-threatening polymorphic ventricular tachyarrhythmias. LQT1 caused by KCNQ1 mutations is the most common form of LQTS.
Methods and Results: Patients diagnosed with LQTS were screened for disease-associated mutations in KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, and SCN5A. A novel mutation was identified in KCNQ1 caused by a three-base deletion at the position 824-826, predicting a deletion of phenylalanine at codon 275 in segment 5 of KCNQ1 (Delta F275). Wild-type (WT) and Delta F275-KCNQ1 constructs were generated and transiently transfected together with a KCNE1 construct in CHO-K1 cells to characterize the properties of the slowly activating delayed rectifier current (IKs) using conventional whole-cell patch-clamp techniques. Cells transfected with WT-KCNQ1 and KCNE1 (1:1.3 molar ratio) produced slowly activating outward current with the characteristics of IKs. Tail current density measured at -40 mV following a two-second step to +60 mV was 381.3 +/- 62.6 pA/pF (n = 11). Cells transfected with Delta F275-KCNQ1 and KCNE1 exhibited essentially no current. (Tail current density: 0.8 +/- 2.1 pA/pF, n = 11, P = 0.00001 vs WT). Cotransfection of WT- and Delta F275- KCNQ1 (50/50), along with KCNE1, produced little to no current (tail current density: 10.3 +/- 3.5 pA/pF, n = 11, P = 0.00001 vs WT alone), suggesting a potent dominant negative effect. Immunohistochemistry showed normal membrane trafficking of Delta F275-KCNQ1.
Conclusion: Our data suggest that a Delta F275 mutation in KCNQ1 is associated with a very potent dominant negative effect leading to an almost complete loss of function of IKs and that this defect underlies a LQT1 form of LQTS.

DOI： 10.1111/j.1540-8167.2007.00889.x

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Language：English   Publisher：ELSEVIER IRELAND LTD  

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergic induced bidirectional or polymorphic ventricular tachycardias. Some of CPVT families were reported to be associated with cardiac ryanodine receptor gene (RyR2) mutations. However, association between RyR2 and other arrhythmogenic disorders is not clarified. In this study, we analyzed 83 Japanese patients including patients with long-QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, arrhythmogenic right ventricular caridiomyopalby and CPVT. Genetic screening of RyR2 revealed 3 distinct mutations among 4 families with CPVT (75% of incidence). However, no mutation was found in other groups. This is the first report to demonstrate prevalence of RyR2 mutations in various arrhythmogenic disorders in Japan. RyR2 mutations were detected frequently in CPVT but not in other diseases. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2006.02.024

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background - Cardiac ion channelopathies are responsible for an ever- increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST- segment elevation in the right precordial ECG leads, a shorter- than- normal QT interval, and a history of sudden cardiac death.
Methods and Results - Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b ( Ca-v beta 2b), CACNA2D1 ( Cav(alpha 2 delta 1)), and CACNA1C tagged with enhanced yellow fluorescent protein ( Ca(v)1.2). Whole- cell patch- clamp studies were performed after 48 to 72 hours. Three probands displaying ST- segment elevation and corrected QT intervals &lt;= 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss- of- function missense mutations in CACNA1C ( A39V and G490R) and CACNB2 ( S481L) encoding the alpha(1)- and beta(2b)- subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Cav1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca-v beta 2b-subunits.
Conclusions - This is the first report of loss- of- function mutations in genes encoding the cardiac L- type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter- than- normal QT intervals.

DOI： 10.1161/CIRCULATIONAHA.106.668392

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: Genetically abnormal action potential duration (APD) can be a cause of arrhythmias that include long and short QT interval syndrome.
Purpose: The aim of this study was to evaluate the arrhythmogenic effect of short QT syndrome induced by the over-expression of Kv1.5 in rat.
Methods: From Sprague-Dawley rats on fetal days 18-19, cardiomyocytes were excised and cultured with and without transfection with the Kv-1.5 gene using an adenovirus vector. The expression of Kv1.5 was proven by immunohistochemistry and Western blot analysis. In the culture dish and in the whole cells, the electrical activities were recorded using the whole-cell patch-clamp technique and the effects of 4-AP and verapamil were tested.,
Results: After transfection with Kvl.5 for 12 h, immunohistochemical staining and Western blot analysis were positive for Kvl.5 while they were negative in the control transfected with only Lac-Z. In the culture dish, the myocytes showed spontaneous beating at 115 beats/min (bpm) just prior to the transfection with Kvl.5 and increased to 367 bpm at 24 h. The control myocytes showed stable beating rates during culturing. 4-AP at 200 mu M slowed down the rate and verapamil abolished the beating. In the whole cells, the maximal resting membrane potential was slightly depolarized and APD was extremely abbreviated both at 50% and 90% of repolarization compared with those of the control. Rapid spontaneous activities were found in a single myocyte with Kv1.5 transfection and 4-AP slowed down the frequency of the activities with a reversal of the shortened APD.
Conclusion: The over-expression of Kv1.5 induced short APD and triggered activities in rat cardiomyocytes. This model can be used to study the arrhythmogenic substrate of short QT syndrome. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2006.05.030

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Background Suppression of implantable defibrillator discharges associated with ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed to investigate the efficacy of intravenous nifekalant hydrochloride in predicting the effects of oral sotalol.
Methods and Results The present study included 14 patients who had sustained VTA associated with structural heart disease. All patients also had inducible VTA. To compare the effects of nifekalant and sotalol, programmed electrical stimulation was performed, in the basal state, after nifekalant administration, and after sotalol administration. Nifekalant and sotalol similarly prolonged the corrected QT interval and ventricular effective refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5 patients whose VTA became non-inducible by nifekalant, subsequent treatment with sotalol also suppressed the inducible VTA. In all of the 9 patients non-responding to nifekalant, VTA remained inducible during sotalol treatment. Nifekalant accurately predicted the response to sotalol during electrophysiologic study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred in 3 non-responders during a follow-up of 46 +/- 11 months.
Conclusions Nifekalant and sotalol had similar effects on inducible VTA. The response of inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INTERNATIONAL HEART JOURNAL ASSOCIATION  

Although catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with fatal ventricular arrhythmias and sudden death, the ECG findings are not fully understood. In this paper, we report on alterations in the U-wave.
Seven patients from 6 families with CPVT in which bidirectional tachycardia and polymorphic VT were induced by exercise or isoproterenol infusion visited our hospitals. VT was not inducible by programmed electrical stimulation. A novel gene mutation of the ryanodine receptor 2 (RyR2) was confirmed in 2 families.
In one of these patients, U-wave alternans was observed following ventricular pacing at 160 beats/min. In the other patient, U-wave alternans was observed during the recovery phase after the exercise stress test, which was terminated because of polymorphic VT. In both cases, leads V-3-V-5 were the leads showing alternans most clearly. In the third patient, a negative U-wave became positive following a pause from sinus arrest and a change in T-wave was also noted.
Since such findings were not found in the other subjects who underwent electrophysiologic study, isoproterenot infusion or exercise stress testing, the phenomenon seems to be relevant to the underlying pathogenesis of CPVT. The genesis and significance of U-wave alteration need to be determined.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: The accumulation of cardiovascular risk factors can be seen in a single person but it needs to be determined if this occurs more frequently than might be explained by mere coincidence.
Methods: This study involved 119,412 adults: 41,8 19 males and 77,593 females, who were 40 years of age or older and who underwent an annual health examination. From the clinical and biochemical data, the actual prevalence of a combination of 3 or more factors: abnormal body mass index (&gt;= 25.0), hypertension, high triglyceride (&gt;= 150 mg/dl), low HDL cholesterol (&lt; 40 mg/dl) and abnormal fasting glucose metabolism (fasting blood sugar &gt;= 110 mg/dl or HbAlc. 5.5%) was determined. Then, the prevalence of a corresponding combination of 3-5 factors was predicted from the prevalence of each factor on the assumption that their combination occurs as a result of coincidence.
Results: The criteria of metabolic syndrome (1-3 risk factors) was met in 17,842 (14.9%) of the examinees. The actual prevalence of any combination of 3-5 factors of metabolic syndrome was more frequent than those expected to occur by coincidence (P &lt; 0.001). When compared with the prevalence of the total examinees, the prevalence of obesity and insulin resistance was 2.5 and 2.9 times higher in metabolic syndrome compared to that in the total examinees but it was 1.7 to 2.1 times higher in hypertension and high triglyceride. The former two were clustering more than hypertension or high triglyceride in metabolic syndrome. Abnormal levels of serum creatinine and total cholesterol were found more often in metabolic syndrome.
Conclusion: Combinations of risk factors of metabolic syndrome were found more frequently than coincidental phenomenon in the subjects from the general Population. These finding suggest that these risk factors do cluster and obesity and insulin resistance were suggested to be linked with metabolic syndrome more than hypertension or high triglyceride. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2005.06.007

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Language：English   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.45.1644

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publisher：ELSEVIER SCI IRELAND LTD  

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT. A 20-year-old male was referred to our hospital because of recurrent syncope after physical and emotional stress. Routine cardiac examinations including catheterization revealed no structural abnormality. Exercise on treadmill induced premature ventricular contraction in bigeminy and bidirectional ventricular tachycardia was induced during isoproterenol infusion. beta-Blocking drug was effective in suppressing the arrhythmias. We performed genetic screening by PCR-SSCP method followed by DNA sequencing, and a novel missense mutation R2401H in RyR2 located in FKBP12.6 binding region was identified. This mutation was not detected in 190 healthy controls. Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. This is the first report of RyR2 mutation in CPVT patient from Asia including Japan. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2003.11.050

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Language：English   Publisher：(一社)日本循環器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN HEART JOURNAL, SECOND DEPT OF INTERNAL MED  

Though Multiple risk factors are commonly observed in patients with ischemic heart disease and associated with an increased risk of developing IHD, it has not yet been proven that risk factors actually occur in combination more frequently than by chance alone.
We tested the hypothesis that if some risk factors occur ill combination, the actual incidences will be higher than the predicted ones which were Calculated oil the assumption that each risk factor Occurs independently and in combination as a result of coincidence.
One hundred consecutive atients were included in this Study. All had significant stenosis or Occlusion of a coronary artery. The ages ranged from 50 to 69 years and only males were studied. From the incidences of the well-established risk factors in IHD: hypertension, impaired glucose tolerance or diabetes mellitus, hypertriglyceridenlia, obesity and hypercholesterolemia, we determined the actual incidences of combinations of risk factors and compared these with the predicted incidences, which were the probability calculated from each risk factor.
Some of the combinations of 2 to 4 risk factors were found significantly more often than the predicted ones. Though not significant, the reverse was the case ill the actual incidence of patients having no risk factors.
Some combinations of well-known risk factors were found more often than the predicted risk factors from the probability and showed a tendency to cluster in coronary artery disease patients. Some linking factor must be involved in this type of occurrence of risk factors.

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We identified a novel mutation Ala178fs/105 missing S3-S6 and C-terminus portions of KCNQl channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1-S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

DOI： 10.1016/j.febslet.2004.08.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

The predictive values for long-term outcome in 127 consecutive patients with acute myocardial infarction (AMI) after successful primary percutaneous transluminal coronary angioplasty (PTCA) were prospectively investigated in the present study. The primary endpoint was a composite of cardiac death, nonfatal AMI, and recurrent angina. Follow-up angiography was performed in 120 patients to assess restenosis. The primary endpoint occurred in 21 patients during a follow-up period of 35+/-24 months. These patients had a higher lipoprotein(a) [Lp(a)] concentration (p=0.0105) and more prevalence of multivessel disease (p=0.0028) than the other patients. The subjects were divided into 2 groups at the 75th percentile Lp(a) value: group A had an Lp(a) concentration greater than or equal to47 mg/dl and group B &lt;47 mg/dl. Kaplan-Meier analysis showed a lower cardiac event-free survival rate in group A (p=0.0007) and in patients with multivessel disease (p=0.001). In Cox proportional hazards regression analysis, an Lp(a) level greater than or equal to47mg/dl (relative risk[RR] 5.5, 95% confidence interval [CI] 2.0-15.0, p=0.0007) and multivessel disease (RR 5.3, 95% CI 2.0-13.7, p=0.0006) were independent predictors of the primary endpoint. An elevated Lp(a) concentration on admission and multivessel disease are significant predictors for long-term adverse outcome in AMI patients treated by primary PTCA.

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Language：English   Publisher：(一社)日本循環器学会  

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Language：Japanese   Publisher：国際医療福祉大学学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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＜文献概要＞Point ・12誘導心電図で,下壁または側壁誘導の2誘導以上で0.1mV以上のJ点上昇を伴う,スラーまたはノッチを認める場合をJ波と定義する.・J波は男性,若年者,アスリート,アフリカ系アメリカ人,アジア人に多く認め,特発性心室細動との関連が報告されている.・一般集団にも認めるが,ハイリスク心電図所見として,高振幅,広範囲の誘導での出現,水平型/下降型のST部分,低いT波,徐脈依存性の振幅の増大などが知られている.

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Language：Japanese   Publisher：国際医療福祉大学学会  

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＜文献概要＞Point ◎虚血性心疾患に伴う致死性不整脈に対しては,植込み型除細動器(ICD)が最も有効かつ確実な治療である.◎除細動機能を有するデバイスはICDのほかに完全皮下植込み型除細動器(S-ICD),着用型自動除細動器(WCD)がある.◎ICD植込み後の不整脈再発により頻回のICD作動がしばしば問題となる.◎カテーテルアブレーションは不整脈再発によるICD作動を抑制するのに有効である.◎マッピング技術の進歩により,カテーテルアブレーションの治療成績は向上している.

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Language：Japanese   Publisher：臨床心臓電気生理研究会  

66歳男性。持続性心房細動に対して左右肺静脈後壁同時隔離と下大静脈三尖弁峡部アブレーション後に反時計方向に旋回するperi-mitral flutterが誘発された。僧帽弁峡部の通電中に頻拍周期が延長し、冠静脈洞(CS)カテーテルの中部で電位が分裂し、CS遠位部は遠位から近位方向へと興奮順序が逆転した。activation mapは左上肺静脈と左房接合部の上前方に最早期興奮部位を有する同心円状の伝導パターンを示した。最早期興奮部位から左房を時計方向に興奮伝播する部位ではpost-pacing interval(PPI)は頻拍周期に一致せず、反時計方向に興奮伝播する部位ではPPIは頻拍周期に一致した。Marshall静脈(VOM)に電極カテーテルを挿入すると、同部位のPPIは頻拍周期に一致し、本症例はperi-mitral flutterが僧帽弁峡部通電中にVOMを介したマクロリエントリーに乗り換えた症例と考えられた。僧帽弁峡部から左房天蓋の最早期興奮部位までは約4.1cmで、その間はVOMと左房間の電気的なコネクションが無いと考えられた。VOMの解剖や左房とのコネクションを考えるうえで貴重な症例と考えた。(著者抄録)

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特発性心室細動における悪性のJ波と一般集団における良性のJ波の特徴を明らかにする手段を確立し、J波のリスク階層化に役立てることを目的とした。研究1として、低体温症患者19人のうち9人でRR間隔の変動を認めた。RR間隔が1353±472から740±391msに短縮すると、J波の振幅は0.50±0.29mVから0.61±0.27mVに減高した。研究2では、心房期外収縮を認めた経皮的冠動脈形成術施行患者のうちJ波を呈した16人、非心臓疾患患者のうちJ波を認めた19人を対象としたところ、虚血性ではJ波は下壁および高位側壁に局在していた。RR間隔が短縮すると虚血性、非虚血性ともにJ波は増嵩していた。研究3として、RR間隔が短縮した際にJ波が新規に出現した23例では、APC後にRR間隔が延長するとJ波は元のレベルに戻った。

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Language：Japanese   Publisher：(株)日本医事新報社  

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＜文献概要＞Point ●Brugada症候群は,1992年にブルガダ(Brugada)兄弟により報告された,心室細動により失神または突然死に至る疾患である.●アジア人,30〜50歳代の男性に多く,典型的な心電図はV1〜V3誘導のST上昇でコーブド型と呼ばれる.●高位肋間やナトリウム(Na)チャネル遮断薬で,コーブド型心電図変化が顕在化しやすい.●約2〜3割の症例で,SCN5A(心臓Naチャネル)の遺伝子変異が検出される.●ハイリスク症例では,植込み型除細動器(ICD)の植え込みが行われる.

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52歳女性、生来健康。歯肉修復物除去のため、クリニックにて歯科治療を受けた。歯科治療中に疼痛の訴えはなかった。止血のため頬粘膜と歯肉の間にエピネフリン含有綿球を使用後に意識消失発作といびき呼吸をきたし脈拍触知不能となったため、心肺蘇生が施行された。AED装着されたが作動せず、当院に救急搬送中に自己心拍が再開した。下壁誘導でのST上昇および心筋逸脱酵素の上昇を認めたが、ニトログリセリン舌下投与でST上昇は消失した。緊急冠動脈造影が施行され、左室造影で下壁の壁運動低下を認めたが冠動脈に有意狭窄は認めなかった。後日のAEDの解析で完全房室ブロックが確認された。以上から、完全房室ブロックを合併した冠攣縮性狭心症による心肺停止と診断した。歯科治療で頻用される通常量のエピネフリンによる冠攣縮性狭心症への関与が示唆された、貴重な症例を経験したため報告する。(著者抄録)

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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＜ポイント＞Naチャネル遮断薬は,時として心房細動を粗動化する(Ic flutter).2:1心房粗動はF波の同定が困難なことがある.ST上昇を見た場合,急性心筋梗塞,心膜炎などをまず鑑別する.Naチャネル遮断薬は,Brugada型心電図を顕在化させる場合がある.(著者抄録)

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症例は47歳男性。生来健康であったが健康診断で洞性徐脈を指摘された。各種検査からは器質的心疾患は否定的であり、家系内に洞不全症候群によるペースメーカ植込み数が多数あり家族性洞不全症候群の診断となった。徐脈に伴う自覚症状が強く出現したため永久ペースメーカを植込み自覚症状の改善を認めた。濃厚な家族歴の背景から遺伝子解析を施行したところラミンA/C変異が見つかった。ラミンA/C変異と洞不全症候群の関連に関しては報告が少なく、変異自体も過去に報告のなかったものであったためここに報告する。(著者抄録)

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CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2015400566

Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：OXFORD UNIV PRESS  

DOI： 10.1093/europace/euv029

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Language：Japanese   Publisher：(公財)日本心臓財団  

生来健康な18歳男性。突然死の家族歴なし。運動中に突然心肺停止となりAEDで蘇生され搬送された。蘇生後の心電図II、III、aVF誘導でT波が陰転化し心エコーで一過性に下壁の壁運動異常を認めた。緊急冠動脈造影を施行、右冠動脈優位であり大動脈左冠尖より起始し、大動脈の前方、肺動脈との間を走行し同部位の圧迫狭窄が疑われた。後日アデノシン3リン酸投与下で冠血流予備量比(FFR)を測定したところ右冠動脈中間部で0.71、大動脈で0.96であった。本例は運動極期に起きた心室細動であるが、イベント後のII、III、aVF誘導での心電図変化と一過性の下壁の壁運動異常、そして冠動脈の所見から右冠動脈領域の虚血から心室細動が惹起されたと診断した。冠動脈起始異常に伴う心室細動の報告例はあるが一般に心筋虚血の再現は困難である。本例では薬物負荷下FFRで有意な狭窄を証明できたため報告する。(著者抄録)

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Language：Japanese   Publisher：臨床心臓電気生理研究会  

79歳、女性。Verapamilで停止するlong RP&#039;頻拍を指摘。右房プログラム刺激で頻拍周期400msecの心房頻拍が誘発された。CARTOマップでは三尖弁論7時方向で最早期興奮を認めた。最早期興奮部位の周囲でentrainment pacingを行うと、右房自由壁からの刺激で冠静脈洞はorthodromic capture、右房、His束のA波はantidromic captureされmanifest entrainmentが確認された。Manifest entrainmentが得られる部位の中で最早期興奮部位に最も近い部位は、約9mm自由壁側に位置し緩徐伝導路の入口部と考えた。同部位よりも中隔側(峡部側)ではA波はすべてantidromic captureされた。想定された緩徐伝導路入口部位から最早期興奮部位にかけてはpost-pacing intervalは頻拍周期に一致した。最早期興奮部位に通電し頻拍は停止、誘発不能となった。Entrainment pacingで9mmの緩徐伝導路長を推定しえたverapamil感受性三尖弁輪起源心房頻拍の1例を経験した。(著者抄録)

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Language：Japanese   Publisher：(株)医学出版  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2015111497

Language：Japanese   Publisher：(株)医学書院  

従来から良性の心電図所見とされてきた完全右脚ブロックは、最近の疫学研究では心血管死と総死亡に関連することが報告されている。特発性心室細動の患者群では完全右脚ブロックを呈する頻度が高いこと、また完全右脚ブロックの合併はブルガダ症候群などの特徴的な心電図変化をマスクすることが明らかである。右脚の構造と生理、右脚ブロックの心電図上の特徴、疫学、突然死との関わり、右脚ブロックと特発性心室細動、ブルガダ症候群と右脚ブロック、背景にある遺伝子異常の存在、今後の展望、について概説した。

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2015128794

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(公財)日本心臓財団  

26歳の女性。生来健康であった。これまでに、失神やアレルギーの既往なく、健康診断で心電図異常を指摘されたことはなかった。また突然死や心疾患の家族歴も認めていない。腟狭窄に対する腟拡張術施行中、止血用3000倍希釈ボスミン7mL(エピネフリン換算2mg)を腟粘膜に局注した直後に、血圧210/116mmHg、心拍数188bpmまで上昇、その後QT時間が延長し、心室性期外収縮が頻発、局注後4分後に心室性期外収縮からtorsade de pointesとなり、心肺停止となった。心臓マッサージ開始後、300Jで電気的除細動を施行し、洞調律に復帰した。直後の心電図では、急性冠症候群を示唆する所見や明らかなQT延長を認めず、電解質も正常範囲内であった。心エコー検査でも明らかな器質的心疾患を認めなかった。しかし、術後2日目の心電図で明らかな要因なくQTcが552msと著明に延長していたため、精査目的で電気生理学的検査が施行された。右室心尖部、右室流出路からのプログラム刺激ではVT/VFは誘発されなかったが、イソプロテレノール負荷にてQTcが375msから535msと著明に延長し、TU波の出現を認めたため、潜在性QT延長症候群と診断した。その後、プロプラノロール30mg内服開始となったが、予測最大心拍数近くまでの運動負荷でも明らかなQT時間の延長を認めなかったため、運動制限、妊娠制限せずに経過観察とし、これまでのところ経過良好である。(著者抄録)

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Language：Japanese   Publisher：(公社)日本人間ドック学会  

J-GLOBAL

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Language：Japanese   Publisher：(株)医学出版  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2014160342

Language：Japanese   Publisher：日本救急医学会-関東地方会  

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Language：Japanese   Publisher：(公財)日本心臓財団  

症例は72歳、男性。2010年6月に胸痛、眼前暗黒感を認め他院を受診。右脚ブロック型右上方軸の心室頻拍(230bpm)を認め電気的除細動を施行した。冠動脈造影で回旋枝に有意狭窄を認め、PCIを施行しICD植え込みを行った。2011年10月にVTによるICD初回作動。抗頻拍ペーシングで停止可能であったが、その後もVTを頻回に認めるため、アブレーション目的で当院に紹介となった。2012年7月にEPS/アブレーションを施行。CARTO soundを用いて左室を構築。側壁基部より中部にかけて菲薄化を伴う壁運動異常領域を認めた。左室造影後、逆行性に左室にマッピングカテーテルを挿入し、洞調律中に左室のvoltage mapを作成。側壁の壁運動異常領域は比較的電位波高は保たれており(&gt;1.5mV)、一部まだらに低電位、分裂電位、遅延電位を認めた。右室からのプログラム刺激ではVTは誘発不能だったが、左室壁運動異常領域からのプログラム刺激により右脚ブロック型右下方軸のVT(CL 338ms)が誘発された。左室壁運動異常領域内で、VT中に拡張期電位(DP-QRS:280ms)を認め、血行動態は不安定であったが短時間のエントレインメントペーシングによりconcealed entrainment(PPI+30)が得られた。洞調律中に同部位から僧帽弁輪まで線状焼灼を行いVTは誘発不能となり終了した。以後3ヵ月間、VTの再発を認めていない。CARTO soundによる壁運動異常領域の同定が、VTの基質同定に有用であったと考えられた。(著者抄録)

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(公財)日本心臓財団  

症例は39歳、男性の発作性心房細動(PAF)症例。父もPAF。突然死の家族歴はない。2008年の健診で心房細動を指摘され当院を紹介受診。心エコー図で僧帽弁逸脱による中等度の僧帽弁逆流症と左房拡大、左室拡大(Dd/Ds=5.8/3.6cm)を認めた。PAFに対するアブレーションを施行したが、両側拡大肺静脈隔離後、三尖弁下大静脈間峡部の通電中に心室細動となり、電気的除細動を施行した。その後のプログラム刺激でも心室細動が誘発された。心臓MRIでは特記すべき所見は認めず、各種薬剤負荷にても有意な心電図変化は認めなかった。2週間後に再度電気生理学的検査を施行したところ、右室からのプログラム刺激で心室細動は誘発されなかった。術後に心房頻拍が出現したため、ベプリジル、ペラパミルを開始し、植込み型除細動器(ICD)植え込みは行わず退院とした。以後、外来にて経過観察を行っていたが、1年8ヵ月後に突然死した。アブレーション中に出現した心室細動が唯一の予測因子であった若年性突然死の症例を報告する。(著者抄録)

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Language：Japanese   Publisher：(公財)日本心臓財団  

症例は拡張相肥大型心筋症の59歳、男性。2001年、持続性の心室頻拍(VT)に対し植込み型除細動器(ICD)植え込み施行。2010年11月、2011年2月にICD頻回作動のため、心臓電気生理学的検査(EPS)/アブレーションを施行。右室流出路および左室心基部に低電位部位を認め、遅延電位およびペースマップを指標にアブレーション施行した。しかしながらEPS中に誘発されなかった、頻拍周期が長く(530ms)QRSの立ち上がりの遅い右脚ブロック型下方軸のclinical VTが再発したため、2011年2月に2回目のアブレーションを施行した。心窩部より心外膜穿刺を行い、洞調律下に心外膜マッピングを施行。心外膜側右室および左室前壁、心基部に低電位部位を認めた。心内膜側のペーシングでは誘発されなかったclinical VTが心外膜側からの刺激により容易に誘発された。VT中に心内膜および心外膜側両方からマッピングを行い、心外膜側前壁基部の低電位部位に長い拡張期電位を認め、同部位でのペーシングにてentrainment with concealed fusionを認め、post pacing intervalも頻拍周期に一致した。同部位への通電によりVTは4秒で停止し、誘発不能となった。近傍の遅延電位に通電を追加し、終了した。以後、VTの再発を認めず、経過良好である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese   Publisher：(公財)日本心臓財団  

症例は49歳、男性。父が33歳時に突然死した。20歳時より高血圧に対して、また、32歳ころより発作性心房細動に対して近医で薬物療法が開始された。発作性心房細動の頻度および持続時間が増加したため、カテーテルアブレーション目的に入院した。入院後、両側肺静脈隔離術を施行。術翌日より発熱、胸痛が出現し心膜炎と診断し、NSAIDsの投薬を行った。術2日後の深夜および未明に心室性期外収縮から心室細動となり停止に自動体外式除細動器(AED)を要した。心室細動発症直前に全誘導でJ波の著明な増高を認めた。一時的ペースメーカー留置、イソプロテレノール持続静注にて心電図変化は徐々に改善し、その後、不整脈イベントを認めなかった。ピルジカイニド負荷試験は陰性。心臓MRIでは左室後壁から側壁にかけて脂肪線維変性、遅延造影効果を認めた。植込み型除細動器(ICD)植え込み術を施行した。心房細動に対するカテーテルアブレーション後に発症したJ波症候群の1例を報告する。(著者抄録)

DOI： 10.11281/shinzo.44.S2_142

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：臨床心臓電気生理研究会  

【症例】68歳、男性。心房細動に対し肺静脈隔離や僧帽弁峡部等のアブレーションを2回行った。2010年11月より心房頻拍が出現した。電気生理検査では頻拍周期は450msec、CS 3-4でdouble potentialを認めた。Post-pacing interval(PPI)はCS1-2で505msec、CS 3-4で510msec、CS9-10で465msec、CS10-11で455msecであった。CARTOでのactivation mapは頻拍周期の73%のみをカバーし、興奮は僧帽弁輪周囲を時計方向に旋回していた。最早期興奮部位は左肺静脈左心耳間のリッジ(PV-LAA ridge)下端に位置し、同部位のPPIは頻拍周期に一致した。本頻拍はマクロリエントリー性ATで、PV-LAA ridgeがcritical pathwayであると考えた。PV-LAA ridgeに対するアブレーションにより頻拍は停止した。【考察】本頻拍は、perimitral flutterと異なり、1.CSの電極では僧帽弁峡部で伝導ブロックがあるように見える。2.僧帽弁峡部部付近のCSでPPIが頻拍周期に一致しない。3.CARTOのactivation mapは頻拍周期のすべてをカバーできない、という特徴を有した。【結語】PV-LAA ridgeがcritical pathwayと考えられた僧帽弁輪を旋回する心房頻拍の1例を経験したので報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

アミオダロン抵抗性心房細動(AF)患者に対するカテーテルアブレーションについて検討した。カテーテルアブレーションを施行したアミオダロン抵抗性AF症例20例を対象とした。カテーテルアブレーションの後、平均観察期間8.7±7.6ヵ月で洞調律維持できた症例は20例中17例であった。カテーテルアブレーション、あるいはアミオダロン投与による合併症は認めなかった。術後洞調律維持症例のうち6例は抗不整脈薬を継続され、このうち2例はアミオダロンを投与されていたが、両症例ともにカテーテルアブレーション施行前から、心室頻拍、心室細動に対して投与された。左房径はカテーテルアブレーション後に有意に低下した。BNP値も低下した。

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Language：Japanese   Publisher：(公財)日本心臓財団  

症例は79歳、男性。2005年、近医で心室性期外収縮を指摘され、ジソピラミドの内服を開始された。前立腺癌の化学療法施行目的で入院中、夕食後の歩行時に立ちくらみを自覚し、非持続性心室頻拍(脈拍110/分、20連発)を認めた。メキシレチン、ピルジカイニドを内服するも、右脚ブロック型下方軸の心室性期外収縮および同形の非持続性心室頻拍が頻発し、カテーテルアブレーションを施行した。同時に施行した冠動脈造影、左室造影は正常であった。CARTOシステムのPaSoを用いて、逆行性アプローチで大動脈弁下部、左冠尖、大心臓静脈からペースマップを行った。大心臓静脈から前室間静脈近位部で良好なペースマップを得たため、左冠動脈を造影しながら静脈内から最大出力25Wで通電した。通電による心室性期外収縮の消失と、通電終了後の再発を繰り返した。そのため、再度左冠尖からペースマップをしたところ、時折perfect matchを認め、また、心室性期外収縮の直前にprepotentialを認めたことから、同部位で通電した。通電により心室性期外収縮は消失し、また、prepotential後の心室性期外収縮も消失したためexit blockが完成したと判断した。その後も再発を認めなかった。前室間静脈近位部と左冠尖からの通電により心室頻拍、心室性期外収縮を根治し得た症例を経験した。(著者抄録)

DOI： 10.11281/shinzo.43.S3_133

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Language：Japanese   Publisher：(株)日本臨床社  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2012113161

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：(公財)日本心臓財団  

心サルコイドーシスは房室ブロックだけでなく心室頻拍や心室細動を合併し、突然死にいたることがある。症例1:61歳、女性。2000年、完全房室ブロックに対しペースメーカー植え込み。術前、左室収縮能軽度低下、Gallium-67citrateシンチグラムにて、心臓への異常集積を認め、心サルコイドーシスが疑われた。他臓器のサルコイドーシス合併はなく、当時の診断基準では、診断にいたらずステロイド治療は行われなかった。約3年後、心不全の急性増悪とともに心室頻拍が頻回に出現し植込み型除細器(ICD)植え込みとなった。症例2:58歳、女性。2007年、完全房室ブロックに対しペースメーカー植え込み。翌年、心エコー上で心室中隔基部の菲薄化ならびにGallium-67citrateシンチグラムにて、心臓への異常集積を認め、肺病変も強く疑われたため、心サルコイドーシスと診断された。ステロイド投与が開始されたが、約1年後に心室細動を発症しICD植え込みとなった。完全房室ブロックにて発症し、ペースメーカー植え込み後、約3年以内にICD植え込み手術が必要となった心サルコイドーシス疑いの2症例を経験した。心サルコイドーシスに対する心臓植え込みデバイスの選択が、困難な症例であり報告する。(著者抄録)

DOI： 10.11281/shinzo.43.S2_46

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Language：English   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：臨床心臓電気生理研究会  

【症例】52歳、男性。主訴は動悸。30年前から動悸発作あり、10年前に近医で発作性心房細動(AF)と診断され抗不整脈薬頓服で経過観察された。5年前から発作頻度が増し、複数の抗不整脈薬が無効であり、アブレーションのため2009年12月14日に当科紹介、入院した。臨床経過中、細動波を伴う心房細動の他、II誘導のP波の高い心房頻拍(AT)の心電図も記録された。術前日に心血管CTを施行したところ、左上肺静脈が左腕頭静脈に還流する部分肺静脈還流異常症(PAPVR)を認め、左腕頭静脈、上大静脈(SVC)は著明に拡張していた。EPS中、SVC内の異常発火を頻回に認め、これが本症例のAT、AFの原因と考えられた。SVC頻拍中にSVC電気的隔離を行ったところ、SVC頻拍は持続し、心房は洞調律に復した。EPS中に通常型心房粗動も認めたため、下大静脈三尖弁輪間峡部の線状焼灼を追加した。術後AT、AFを認めていない。【考察】PAPVRは極めて発生率が低く、その中でも本症例のように左上肺静脈が左腕頭静脈に接続する症例は稀有である。本症例はQp/Qs=2.57と高値であり、容量負荷によりSVCが拡張し異常自動能を生ずるようになったと考えられる。SVCを電気的隔離することによりAT、AFを根治し得た。【結語】AFを合併したPAPVRの貴重な1例を経験したので報告する。(著者抄録)

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Language：Japanese   Publisher：(株)メディカル・サイエンス・インターナショナル  

心臓は、(1)心房が収縮して、その後に心室が収縮する。また、(2)右室と左室は同時に収縮し、そして(3)心室の中隔と自由壁も同時に向かい合って収縮する。何を当たり前のことをと思われるかもしれないが、この3つのタイプの心臓の同期がうまくいかない病態が心不全を思いのほか悪化させていることが最近の画像診断技術の進歩でわかってきた。この病態を同期不全dyssynchronyと呼び、正常の刺激伝導系を介して心房や心室が順序通りに興奮せず、(1)心房-心室間、(2)左室-右室間、(3)心室内、で伝導障害が出現していることを意味する。この同期不全の一番わかりやすい病態が、VVI(非生理的)ペーシングとDDD(生理的)ペーシングとの比較である。伝導障害に対して使用されるペースメーカのペーシングモードは、歴史的には非生理的ペーシングから、より生理的なペーシングへと移行してきた。しかし実は大規模臨床試験の結果から、両者の間で生命予後や心不全発症に差はないことが示されている。さらに、最も生理的なモードであるDDDRペーシングを行ったとしても、洞調律に比べて心不全による入院・死亡率が悪化することが示されている。現在ではペーシングモードそのものよりも、むしろ生理的ペーシング・非生理的ペーシングを問わず必須となる右室心尖部へのペーシングが同期不全をもたらし、心機能低下、心房細動の発生率上昇、および生命予後悪化へとつながることが問題となっている。ここ数年、重症心不全症例における心室間同期不全に対する治療として心臓再同期療法cardiac resynchronization therapy(CRT)が導入され、QOL、心不全入院率、生命予後の改善効果が複数の大規模臨床試験で示されてきた。本稿ではこれらを踏まえて、今後の心不全治療に重要となってくるであろう同期不全の概念について概説する。同期不全の病態生理について、まず房室同期不全と心室内同期不全について説明し、続いて心室間同期不全について述べる。(著者抄録)

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2011047407

Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(公財)日本心臓財団  

軽度低体温療法は心停止蘇生後の神経学的予後ならびに生命予後を改善し得ることが知られている。一方で、低体温中はQT間隔が延長するため、蘇生後のQT延長症候群(LQTs)に対する軽度低体温療法は、QT間隔をさらに延長し催不整脈作用を呈する可能性がある。今回われわれは、院外心停止からの蘇生後、意識障害が遷延し軽度低体温療法が施行されたLQTsの3例を経験したので報告する。2例は遺伝性、1例は薬剤誘発性であった。全例ともに、体温の低下とともにQT間隔はさらに延長し、低体温療法中に最長のQT間隔が記録された。一方、復温終了後もQT延長は遷延した。1例では復温中にtorsade de pointesの再発を認めたが、3例ともに神経学的後遺症なく回復し、軽快退院した。LQTsの院外心停止例に対する軽度低体温療法により、QT間隔を延長し心室頻拍が再発する可能性はあるが、同療法による神経学的予後の改善は期待し得ることが示唆された。(著者抄録)

DOI： 10.11281/shinzo.42.S2_106

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

26歳男。患者は車を運転中に意識消失を来し、自損事故となった。救急隊到着時、心肺停止状態で、救急搬送後は再発性のVF発作を来し、急性冠症候群または冠攣縮等の虚血の関与も考慮された。だが、明らかな虚血性心電図変化はなく、まず血行動態の安定化、脳保護を優先した。搬送時の心電図ではQT延長は明らかでなかったが、幼少時からQT延長を指摘されていたとの情報があり、先天性QT延長症候群を強く疑って対処した。しかし、心拍再開後も意識障害が遷延したため、軽度低体温療法が行われ、意識レベルが徐々に回復後、諸検査が行われた。その結果、ピルジカイニド負荷ではV1-2誘導でcoved型のST上昇を認め、Brugada症候群の合併が考えられた。そこで、NaチャネルSCN5A遺伝子を中心にスクリーニングを行い、E1784K変異が判明し、LQT3とBrugada症候群両者の特性持っていることが示唆された。以後、諸症状から本症例では治療として植え込み型除細動器移植術が施行された。

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Language：Japanese   Publisher：臨床心臓電気生理研究会  

上大静脈(SVC)の電気的隔離は横隔神経麻痺を合併することがあり、ときに困難である。Noncontact mapping(NCM)を用いてSVCの電気的隔離を行った2例を報告する。【症例1】51歳、男性。多剤抵抗性の発作性心房細動(AF)。2008年4月1日に両側拡大肺静脈電気的隔離術(PVI)を施行、同年5月28日に再度PVIを行ったが翌29日SVC起源のPACからAFが出現し、同日SVCを電気的隔離した。10月17日に再発、12月9日にアブレーション施行。その際NCMを用いSVCペーシング中のSVC-右房(RA)伝導部位の右房端を同定し、SVC電気的隔離に成功。なお、洞調律中のSVC最早期興奮部位は、SVCペーシング中のRA最早期興奮部位よりSVC内に22mm入った部位であった。【症例2】48歳、女性。2年来の多剤抵抗性のPAF。2008年11月13日に両側拡大PVI施行したが翌日SVC起源のPACからAFが再発、同月19日に2回目のアブレーションを施行。リング状カテーテルをSVCに留置しSVC隔離を行ったがadenosine triphosphate(ATP)静注直後10秒間のみRA-SVC伝導を認めた。EnSiteを用いATP投与時の一過性の右房-SVC伝導部位を同定、通電しSVC電気的隔離に成功した。【結語】SVC起源の発作性AFに対するSVC電気的隔離の際にEnSiteを用いることによりRA-SVC間の伝導部位を正確に同定しえた2例を経験した。(著者抄録)

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

症例は72歳女性、9年来の発作性心房細動。2007年3月カテーテルアブレーションを施行されたが心房細動が再発したため、同年12月に2回目のアブレーションを施行し、再度左右の上下肺静脈を電気的隔離した。その後、心房細動発作は消失したが、2008年3月に、心房頻拍が発作性に出現するようになったため、同年4月に3回目のアブレーションを施行した。無投薬下では右下肺静脈のみに伝導再開を認め、イソプロテレノールおよびアデノシン三リン酸(ATP)の静注時のみ右上肺静脈に一過性の伝導再開を認めた。臨床的に認められた心房頻拍は右肺静脈起源と考えられ、再度右上下肺静脈を電気的隔離した。最終的にイソプロテレノールおよびATP静注でも右上肺静脈左房間の伝導を認めなくなり、その後不整脈の再発なく経過している。前回のアブレーションから4ヵ月後、ATP静注時にのみ右上肺静脈左房間の伝導を認め、それが臨床的な心房頻拍の原因となっていた。慢性期にもATPによって伝導が再開する機能性ブロックが起こりうること、ブロックの確認にATPが重要であることが示唆された。(著者抄録)

DOI： 10.5105/jse.30.73

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Other Link： http://search.jamas.or.jp/link/ui/2010146094

Language：Japanese   Publisher：(株)医学書院  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2010069559

Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(株)メディカル・サイエンス・インターナショナル  

CiNii Books

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(株)最新医学社  

2008年版に改訂された日本循環器学会(JCS)の心房細動治療ガイドラインでは,J-RHYTHM試験の結果を踏まえ,孤立性・発作性心房細動の治療は第1選択としてNaチャネル遮断薬を用いてリズムコントロールを行うことが推奨されている.一方,孤立性・持続性心房細動および器質的病的心に伴う心房細動に対しては,アップストリーム治療を優先したうえでレートコントロールをまず行い,必要があればリズムコントロールを行う.(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2009288117

Language：Japanese   Publisher：(公財)日本心臓財団  

冠攣縮性狭心症は致死性不整脈を合併することがある。胸痛を伴わない無症候性冠攣縮による心停止が疑われた4例を経験したので報告する。年齢は平均49歳(20〜66歳)、男3例;女1例。全例、喫煙者であり、糖尿病の既往はなし。2例では失神の既往あり。全例日中心停止にいたり、2例は安静時、2例は労作時であった。2例では心室細動が記録された。1例ではモニター上ST上昇に引き続き、完全房室ブロックから心室細動へ移行したが、動脈硬化性冠動脈病変は認めなかった。同1例を除く残り3例ではAch負荷試験により両側冠動脈の攣縮が誘発され、電気生理学的検査では心室細動は誘発されなかった。全例でST上昇時もしくはAch負荷試験中も含め、経過中胸痛は認めなかった。心停止をきたした無症候性冠攣縮症例4例を経験したので報告した。原因不明の心臓突然死例では、胸痛の先行や既往がなくても冠攣縮を鑑別する必要性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：English   Publisher：Japanese Circulation Society  

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Language：Japanese   Publisher：(株)メジカルビュー社  

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Language：Japanese   Publisher：(公財)日本心臓財団  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：福田記念医療技術振興財団  

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