Nobuhiro Nishii

Okayama University, Okayama, Okayama, Japan

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Publications (42)197.17 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: This study aimed to determine the usefulness of the combination of several electrocardiographic (ECG) markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). Detection of high/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several ECG markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. Baseline characteristics of 246 consecutive patients (236 males; mean age, 47.6±13.6 years) with Brugada type ECG, including 13 patients with a history of VF and 40 patients with a history of syncopal episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in one patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events. By univariate analysis, history of VF, history of syncopal episodes, paroxysmal atrial fibrillation , spontaneous type 1 pattern in the precordial leads, ECG markers of depolarization abnormalities (PQ >200 ms, QRS duration ≥120 ms, and fragmented QRS [f-QRS]), and those of repolarization abnormalities (infero-lateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. By multivariable analysis, history of VF, history of syncopal episodes, infero-lateral ER pattern, f-QRS were independent predictors of documented VF and SCD (odds ratio, 19.61, 28.57, 2.87, and 5.21, respectively, P<0.05). Kaplan-Meier curves showed that the presence/absence of infero-lateral ER and f-QRS provided a worse/better prognosis (log-rank test, P<0.01). The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients.
    Journal of the American College of Cardiology 03/2014; · 14.09 Impact Factor
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    ABSTRACT: Objectives This study aimed to determine the usefulness of the combination of several electrocardiographic (ECG) markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). Background Detection of high/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several ECG markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. Methods Baseline characteristics of 246 consecutive patients (236 males; mean age, 47.6±13.6 years) with Brugada type ECG, including 13 patients with a history of VF and 40 patients with a history of syncopal episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in one patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events. Results By univariate analysis, history of VF, history of syncopal episodes, paroxysmal atrial fibrillation , spontaneous type 1 pattern in the precordial leads, ECG markers of depolarization abnormalities (PQ >200 ms, QRS duration ≥120 ms, and fragmented QRS [f-QRS]), and those of repolarization abnormalities (infero-lateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. By multivariable analysis, history of VF, history of syncopal episodes, infero-lateral ER pattern, f-QRS were independent predictors of documented VF and SCD (odds ratio, 19.61, 28.57, 2.87, and 5.21, respectively, P<0.05). Kaplan-Meier curves showed that the presence/absence of infero-lateral ER and f-QRS provided a worse/better prognosis (log-rank test, P<0.01). Conclusions The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
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    ABSTRACT: In several cases with idiopathic ventricular fibrillation (VF), VF was initiated by premature ventricular contractions (PVCs) from the Purkinje system. However, the precise characteristics of the Purkinje activity in patients with idiopathic VF remain unclear. We performed an electrophysiological study in a patient with idiopathic VF and examined the correlation between the Purkinje potential and the incidence of PVCs/polymorphic ventricular tachycardia (PMVT). In this case of idiopathic VF, the Purkinje activity caused multiform PVCs and PMVT. The The Purkinje activity and slow conduction of Purkinje fibers are associated with the occurrence of multiform PVCs and PMVT.
    Internal Medicine 01/2014; 53(7):725-8. · 0.97 Impact Factor
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    ABSTRACT: Background- We investigated the acute effects of implantable cardioverter-defibrillator shock on myocardium, cardiac function, and hemodynamics in relation to left ventricular systolic function. Methods and Results- We studied 50 patients who underwent implantable cardioverter-defibrillator implantation and defibrillation threshold (DFT) testing: 25 patients with left ventricular ejection fraction (LVEF) ≥45% and 25 patients with LVEF <45%. We measured cardiac biomarkers (creatine kinase, creatine kinase-MB, myoglobin, cardiac troponin T and I, and N-terminal probrain natriuretic peptide). Left ventricular relaxation was assessed by global longitudinal strain rate during the isovolumetric relaxation period using speckle-tracking echocardiography. Blood sampling and echocardiography were performed before, immediately after, and 5 minutes and 4 hours after DFT testing. Mean arterial pressure was measured directly during DFT testing. Cardiac biomarkers showed no significant changes in either group. LVEF was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in the group with reduced LVEF (P<0.001), whereas LVEF reduction was not observed in the group with preserved LVEF (P=0.637). Global isovolumetric relaxation period was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in both groups (preserved LVEF: 0.39±0.14 versus 0.23±0.13* versus 0.23±0.13* versus 0.40±0.13 s(-1), *P<0.001 versus baseline; reduced LVEF: 0.15±0.05 versus 0.08±0.04† versus 0.09±0.04† versus 0.15±0.05 s(-1), †P<0.001 versus baseline, repeated-measures ANOVA). Time to recovery of mean arterial pressure to the baseline was prolonged in the group with reduced LVEF (P<0.001). Conclusions- Implantable cardioverter-defibrillator shock transiently impairs cardiac function and hemodynamics especially in patients with systolic dysfunction, although significant tissue injury is not observed.
    Circulation Arrhythmia and Electrophysiology 07/2012; 5(5):898-905. · 5.95 Impact Factor
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    ABSTRACT: Syncope in patients with Brugada syndrome is usually associated with ventricular tachyarrhythmia, but some episodes of syncope can be related to autonomic disorders. The purpose of this study was to investigate the characteristics of syncope to differentiate high-risk syncope episodes from low-risk events in patients with Brugada syndrome. We studied 84 patients with type 1 electrocardiogram and syncope. Patients were divided into 2 groups: patients with prodrome (prodromal group; n = 41) and patients without prodrome (nonprodromal group; n = 43). Ventricular fibrillation (VF) was documented at index event in 19 patients: 4 patients (21%) with documented VF experienced a prodrome prior to the onset of VF, whereas 15 patients (79%) did not have symptoms prior to documented VF (P <.01). Twenty-seven patients in the prodromal group and 7 patients in the nonprodromal group were considered to have syncope related to autonomic dysfunction. Syncope in other patients was defined as unexplained syncope. During the follow-up period (48 ± 48 months), recurrent syncope due to VF occurred in 13 patients among patients with only unexplained syncope and was more frequent in the nonprodromal group (n = 10) than in the prodromal group (n = 3; P = .044). In multivariate analysis, blurred vision (hazard ratio [HR] 0.20) and abnormal respiration (HR 2.18) and fragmented QRS (HR 2.39) were independently associated with the occurrence of VF. Syncope with prodrome, especially blurred vision, suggests a benign etiology of syncope in patients with Brugada syndrome.
    Heart rhythm: the official journal of the Heart Rhythm Society 11/2011; 9(5):752-9. · 4.56 Impact Factor
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    ABSTRACT: Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.
    The Journal of Physiological Sciences 09/2011; 61(6):507-13. · 1.09 Impact Factor
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    ABSTRACT: Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. Treatment with imatinib (0.1 to 10 μg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 μg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 μmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.
    International journal of cardiology 03/2011; 159(2):100-6. · 7.08 Impact Factor
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    ABSTRACT: Patients with Brugada syndrome (BS) often have spontaneous changes in their electrocardiogram (ECG). To evaluate the significance of ECG alterations, we investigated the relationships between the ECG and the occurrence of ventricular fibrillation (VF) in both patients and an experimental model of BS. In study 1, we evaluated ECG alterations in BS patients with (VF+, n = 33) and without (VF-, n = 41) spontaneous VF. We defined type 0 ECG as coved-type ST elevation without a negative T wave, which represents the existence of loss-of-dome (LOD) type action potentials (APs). In study 2, we optically mapped epicardial APs and recorded transmural ECGs in 34 canine right ventricular tissues with a drug-induced BS model by a combination of pinacidil and pilsicainide. In study 1, changes in ST level ≥0.2 mV were more frequent in the VF+ group than in the VF- group (P <.01). Spontaneous ECG alterations and appearances of types 1 and 0 ECGs were more frequent in the VF+ group than in the VF- group (P <.01). In study 2, BS model with spike-and-dome (SAD) epicardial APs exhibited type 1 ECG. Deepening of the phase 1 notch of the APs induced heterogeneous conversion of the APs (SAD→LOD) and resulted in ECG conversion from type 1 to type 0. Significant AP heterogeneity often appeared during AP alterations and initiated phase 2 reentry. Tissues having ventricular tachycardia (VT; n = 20) had more frequent alterations in APs and ECG than in tissues without VT (n = 14; P <.01). ECG alterations, especially conversion between types 0 and 1, are associated with significant AP heterogeneity that can initiate VF in BS.
    Heart rhythm: the official journal of the Heart Rhythm Society 02/2011; 8(7):1014-21. · 4.56 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
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    ABSTRACT: It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF. We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia. Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF.
    PLoS ONE 01/2011; 6(5):e19897. · 3.73 Impact Factor
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    ABSTRACT: A 45-year-old man with dilated cardiomyopathy was admitted to our hospital due to congestive heart failure (CHF). Despite the optimal medical treatment, his condition had not improved because of severe left ventricular dysfunction. Because he experienced non-sustained ventricular tachycardia (VT), a biventricular implantable cardioverter-defibrillator (Bi-V ICD) was implanted for reduction of dyssynchrony and primary prevention of lethal tachyarrhythmia. After discharge, he developed CHF and was transported to our hospital by ambulance. In the ambulance, monomorphic sustained VT with 200 bpm suddenly occurred. The ICD detected it as fast VT and anti-tachycardia pacing (ATP) was delivered. After the ATP therapy, RR intervals of VT became irregular and prolonged. Ventricular fibrillation-like electrical activity was recorded by a far-field electrogram from the defibrillator, but the tachycardia cycle length exceeded 400 ms which is under the tachycardia detection rate. The device failed to deliver a shock and the patient had to be rescued with an external shock. This is a rare case of fast VT that degenerated into undetectable life-threatening tachyarrhythmia by ATP.
    Journal of Cardiology Cases 12/2010; 2(3):e159–e162.
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    ABSTRACT: Acquired long QT syndrome (LQTS) is a disease due to a secondary repolarization abnormality induced by various predisposing factors. In contrast to congenital LQTS, risk factors that produce acquired LQTS include organic heart diseases that often exhibit depolarization abnormality. Although various repolarization parameters have been evaluated in acquired LQTS, the existence of depolarization abnormality in association with torsades de pointes (TdP) has not been reported. The purpose of this study was to evaluate both repolarization (QT components) and depolarization parameters (fragmented QRS [fQRS]) in acquired LQTS patients with markedly prolonged QT interval. Seventy patients with acquired severe QT prolongation (QTc ≥ 550 ms) were studied. Thirty-two patients had syncope or TdP (syncope group). Thirty-eight patients did not have any symptoms (asymptomatic group). The existence of fQRS and QT components (QT, QTc, Tpe [interval between peak and end of T wave] intervals, and U-wave voltage) was analyzed. The syncope group had more frequent fQRS (81%) than did the asymptomatic group (21%, P < .01) and the incidence of fQRS was not different before and after removal of predisposing factors. The incidence of organic heart disease was not different between the two groups. No differences in QTc interval were noted between the syncope and asymptomatic groups, although the syncope group had longer QT and Tpe intervals and higher U wave than the asymptomatic group (P < .01). Acquired predisposing factors promoted repolarization abnormality (especially prolongation of QT and Tpe intervals), and the existence of fQRS had an important role in the development of TdP in patients with acquired LQTS.
    Heart rhythm: the official journal of the Heart Rhythm Society 12/2010; 7(12):1808-14. · 4.56 Impact Factor
  • Journal of the American College of Cardiology 12/2010; 56(25):2143-5. · 14.09 Impact Factor
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    ABSTRACT: Mutations in SCN5A are reportedly linked to Brugada syndrome (BS), but recent observations suggest that they are not necessarily associated with ventricular fibrillation (VF) in BS patients. Therefore, the clinical importance of SCN5A mutations in BS patients was examined in the present study.  The 108 BS patients were examined for SCN5A mutations and various parameters were compared between patients with and without mutations. An implantable cardioverter defibrillator (ICD) was implanted in 49 patients and a predictor of appropriate ICD shock was investigated. The existence of a SCN5A mutation was not associated with initial VF episodes (21.7% vs 20.0%, P=0.373). In the secondary prevention group, appropriate shock-free survival rate was significantly lower in patients with spontaneous type 1 ECG than in those without (41.1% vs 85.7% at 2 years, P=0.014). The appropriate shock-free survival rate was also significantly lower in patients with SCN5A mutations than in those without (28.6% vs 83.3% at 1 year, P=0.040). Appropriate shock was more frequent in patients with SCN5A mutations than in those without (6.6±6.2 vs 1.7±3.0, P=0.007). SCN5A mutations are associated with early and frequent VF recurrence, but not with initial VF episodes. This is the first report on the genotype-phenotype interaction and clinical significance of this mutation.
    Circulation Journal 10/2010; 74(12):2572-8. · 3.58 Impact Factor
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    ABSTRACT: It has been reported that bepridil prevents ventricular fibrillation (VF) in patients with Brugada syndrome, but the comparative efficacy with and without mutation in the SCN5A gene has not been elucidated. The purpose of this study was to assess the efficacy of low-dose bepridil (100 mg/day) for VF prevention in patients with Brugada syndrome with and without SCN5A mutation. Among 130 patients with Brugada-type electrocardiogram (ECG), low-dose bepridil was administered to seven patients because of repetitive VF episodes, including three with and four without SCN5A mutation. Preventive effect for VF recurrence and changes of the ECG and the signal-averaged ECG were evaluated. Frequencies of VF episodes were reduced after treatment with low-dose bepridil in all three patients with the SCN5A mutation (before: 0.33 versus after: 0.02 episodes/month, P < 0.01), but not in all four patients without the SCN5A mutation (before: 0.43 versus after: 2.94 episodes/month, P = nonsignificant). Levels of ST-segment elevation at J points and duration of low-amplitude signals less than 40 µV in the terminal filtered QRS complex (LAS40) in signal-averaged ECG were improved exclusively in patients with the SCN5A mutation. Treatment with bepridil prevented recurrence of VF along with improvement of ST elevation and LAS40 in patients with Brugada syndrome with the SCN5A mutation.
    Journal of cardiovascular pharmacology 10/2010; 56(4):389-95. · 2.83 Impact Factor
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    ABSTRACT: This study sought to examine the action potential duration restitution (APDR) property and conduction delay in Brugada syndrome (BrS) patients. A steeply sloped APDR curve and conduction delay are known to be important determinants for the occurrence of ventricular fibrillation (VF). Endocardial monophasic action potential was obtained from 39 BrS patients and 9 control subjects using the contact electrode method. Maximum slopes of the APDR curve were obtained at both the right ventricular outflow tract (RVOT) and the right ventricular apex (RVA). The onset of activation delay (OAD) after premature stimulation was examined as a marker of conduction delay. Maximum slope of the APDR curve in BrS patients was significantly steeper than that in control subjects at both the RVOT and the RVA (0.77 +/- 0.21 vs. 058 +/- 0.14 at RVOT, P = 0.009; 0.98 +/- 0.23 vs. 0.62 +/- 0.16 at RVA, P = 0.001). The dispersion of maximum slope of the APDR curve between the RVOT and the RVA was also larger in BrS patients than in control subjects. The OAD was significantly longer in BrS patients than in control subjects from the RVOT to RVA and from the RVA to RVOT (from RVOT to RVA: 256 +/- 12 vs. 243 +/- 7 ms, P = 0.003; from RVA to RVOT: 252 +/- 11 vs. 241 +/- 9 ms, P = 0.01). Abnormal APDR properties and conduction delay were observed in BrS patients. Both repolarization and depolarization abnormalities are thought to be related to the development of VF in BrS patients.
    Europace 04/2010; 12(4):544-52. · 2.77 Impact Factor
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    ABSTRACT: Brugada syndrome is a disease known to cause ventricular fibrillation with a structurally normal heart and is linked to SCN5A gene mutation. However, the mechanism by which ventricular fibrillation develops in cases of Brugada-type electrocardiogram without SCN5A mutation has remained unclear. Recently, oxidative stress has been implicated in the pathophysiology of cardiac arrhythmia. We also investigated oxidative stress levels in the myocardia of patients with Brugada-type electrocardiogram. Endomyocardial biopsy samples were obtained from 68 patients with Brugada-type electrocardiogram (66 males and two females). We performed histological and immunohistochemical analyses for CD45, CD68, and 4-hydroxy-2-nonenal-modified protein, which is a major lipid peroxidation product. SCN5A mutation was detected in 14 patients. Ventricular fibrillation was documented in three patients with SCN5A mutation and in 11 without SCN5A mutation. In patients with SCN5A mutation, 4-hydroxy-2-nonenal-modified protein-positive area was not significantly different between the documented ventricular fibrillation (VF) group (VF+ group) and the group without documented VF (VF- group). However, in patients without SCN5A, the area was significantly larger in the VF+ group than that in the VF- group (P<.05). All other parameters (fibrosis area, CD45, and CD68) were not different between the VF+ and VF- group in both SCN5A+ and SCN5A- patients. Oxidative stress is elevated in the myocardium of patients with Brugada-type electrocardiogram who have VF episodes and do not have SCN5A gene mutations. Oxidative stress may be associated with the occurrence of VF in patients with Brugada-type electrocardiogram without SCN5A mutation.
    Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 03/2010; 20(1):e37-42. · 1.63 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) often occurs in Brugada syndrome (BrS), and BrS patients with spontaneous AF often experience ventricular fibrillation (VF) attacks. Atrial vulnerability providing a substrate for AF is known to be enhanced in BrS, but there are no data on atrial structural attributes. The objective of this study was to assess atrial electrophysiological and structural characteristics in BrS and their relationships with gene mutations. We studied 57 patients with BrS. Intra-atrial conduction time (CT) was defined as the interval from the stimulus at the high right atrium to atrial deflection at the distal portion of the coronary sinus. Left atrial volume index (LAVI) was measured by the modified Simpson method at left ventricular end-systole using echocardiography. SCN5A mutations were analyzed in all patients. In patients with documented VF, spontaneous AF frequently occurred and prolonged CT and increased LAVI were observed compared with those in patients without VF (all P < .05; LAVI: 22 +/- 5 vs. 32 +/- 7 ml/m(2)). Even among patients without AF, CT and LAVI were still increased in patients with VF (all P < .05; LAVI: 22 +/- 5 vs. 29 +/- 5 ml/m(2)). The presence of SCN5A mutation was associated with prolonged CT (P < .05) and increased LAVI (P < .01), but not with arrhythmic episodes. Both atrial vulnerability and structural remodeling are enhanced in high-risk patients with BrS, even in those without AF. These morphological characteristics suggest that BrS is a form of genetic myocardial disease.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2010; 7(2):218-24. · 4.56 Impact Factor
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    ABSTRACT: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca(2+) overload. Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (.OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2', 7'-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca(2+) concentration ([Ca(2+)](i)) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 micromol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H(2)O(2)), significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture. Carvedilol, a beta-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture, but propranolol had no effect on either [Ca(2+)](i) increase or hypercontracture. HNE induces the formation of ROS, especially H(2)O(2) and .OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.
    Journal of cardiac failure 10/2009; 15(8):709-16. · 3.25 Impact Factor
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    ABSTRACT: Repolarization abnormality, especially during bradycardia, might be critical for initiation of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS), but the contribution of the rate-dependent repolarization dynamics to the occurrence of VF is still unknown. The aim of our study was to determine the differences in rate-dependent repolarization dynamics between BrS with and without spontaneous VF and between BrS with and without SCN5A mutation. The subjects were 37 BrS patients with VF (VF(+) group: 10 male subjects) and without VF (VF(-) group: 27 male subjects) and 20 control subjects. Genetic analysis of SCN5A was performed in all 37 BrS patients. The relationships between QT, QTp, Tp-e, and RR intervals were obtained from Holter recordings as first linear regression lines, and the slopes of QT/RR, QTp/RR, and Tp-e/RR linear regression lines as the sensitivity of rate-dependent repolarization dynamics were compared. QT/RR and Tp-e/RR slopes showed loss of a rate-dependent property in the VF(+) group compared with those in the VF(-) and control groups. There was no significant difference in QTp/RR slope among the VF(+), VF(-) and control groups. The Tp-e interval had a negative correlation with the RR interval in the VF(+) group and a positive correlation with the RR interval in the VF(-) and control groups. There was no significant difference in QT/RR, QTp/RR, and Tp-e/RR slopes between BrS patients with SCN5A mutation and those without SCN5A mutation. Loss of rate-dependent QT dynamics may be associated with occurrence of VF in BrS.
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2009; 6(8):1163-9. · 4.56 Impact Factor