Shigeki Hiramatsu

Atrial Fibrillation in Patients With Brugada Syndrome : Relationships of Gene Mutation, Electrophysiology, and Clinical Backgrounds

OBJECTIVES The goal of our work was to examine the relationships of atrial fibrillation (AF) with genetic, clinical, and electrophysiological backgrounds in Brugada syndrome (BrS). BACKGROUND Atrial fibrillation is often observed in patients with BrS and indicates that electrical abnormality might exist in the atrium as well as in the ventricle. SCN5A, a gene encoding the cardiac sodium channel, has been reported to be causally related to BrS. However, little is known about the relationships of atrial arrhythmias with genetic, clinical, and electrophysiological backgrounds of BrS. METHODS Seventy-three BrS patients (49 +/- 12 years of age, men/women = 72/1) were studied. The existence of SCN5A mutation and clinical variables (syncopal episode, documented ventricular fibrillation [VF], and family history of sudden death) were compared with spontaneous AF episodes. Genetic and clinical variables were also compared with electrophysiologic (EP) parameters: atrial refractory period, interatrial conduction time (CT), repetitive atrial firing, and AF induction by atrial extra-stimulus testing. RESULTS Spontaneous AF occurred in 10 (13.7%) of the BrS patients and SCN5A mutation was detected in 15 patients. Spontaneous AF was associated with higher incidence of syncopal episodes (60.0% vs. 22.2%, p < 0.03) and documented VF (40.0% vs. 14.3%, p < 0.05). SCN5A mutation was associated with prolonged CT (p < 0.03) and AF induction (p < 0.05) in EP study, but not related to the spontaneous AF episode and other clinical variables. In patients with documented VF, higher incidence of spontaneous AF (30.8% vs. 10.0%, p < 0.05), AF induction (53.8% vs. 20.0%, p < 0.03), and prolonged CT was observed. CONCLUSIONS Spontaneous AF and VF are closely linked clinically and electrophysiologically in BrS patients. Patients with spontaneous AF have more severe clinical backgrounds in BrS. SCN5A mutation is associated with electrical abnormality but not disease severity.

Longer Repolarization in the Epicardium at the Right Ventricular Outflow Tract Causes Type 1 Electrocardiogram in Patients With Brugada Syndrome

OBJECTIVES We examined the relationship between repolarization abnormality and coved-type ST-segment elevation with terminal inverted T-wave (type 1 electrocardiogram [ECG]) in patients with Brugada syndrome (BrS). BACKGROUND Recent experimental studies have suggested that accentuation of the right ventricular action potential (AP) notch preferentially prolongs epicardial AP causing inversion of the T-wave. METHODS In 19 patients with BrS and 3 control subjects, activation-recovery intervals (ARIs) and repolarization times (RTs) in the epicardium and endocardium were directly examined with the use of local unipolar electrograms at the right ventricular outflow tract. Surface ECG, ARI, and RT were examined before and after administration of pilsicainide. RESULTS Type 1 ECG was observed in 10 of the 19 BrS patients before the administration of pilsicainide and in all of the 19 patients after the administration of pilsicainide. We found that ARI and RT in the epicardium were shorter than those in the endocardium in all 9 BrS patients without type 1 ECG under baseline conditions and in all control subjects regardless of pilsicainide administration. However, longer epicardial ARI than endocardial ARI was observed in 8 of the 10 BrS patients manifesting type 1 ECG under baseline conditions and in all of the BrS patients after the administration of pilsicainide. Also, epicardial RT was longer than endocardial RT in all patients manifesting type 1 ECG regardless of pilsicainide administration. CONCLUSIONS Our data provide support for the hypothesis that the negative T-wave associated with type 1 BrS ECG is due to a preferential prolongation of the epicardial AP secondary to accentuation of the AP notch in the region of the right ventricular outflow tract.

Prevalence and Characterization of Pulmonary Vein Variants in Patients With Atrial Fibrillation Determined Using 3-Dimensional Computed Tomography

Although several branching patterns of pulmonary veins (PVs) were reported, their prevalence and characterization were not sufficiently clarified. Multislice computed tomography was performed in 428 patients who underwent catheter ablation for drug-refractory atrial fibrillation. Size and branching pattern of PVs were analyzed. A typical pattern of 4 PVs with 4 separate ostia was found in 326 patients (76%). However, a common PV trunk, defined as a PV with coalescence of superior and inferior PVs > or =1.5 cm proximal to the junction with the left atrium, was found on the left side in 34 patients (8%) and right side in 3 patients (0.76%). A discrete middle PV was found on the right side in 54 patients (13%) and left side in 9 patients (2%). A right top PV, defined as an anomalous insertion of a branch of the right superior PV into the left atrial body, was also found in 16 patients (4%). In conclusion, 24% of our patients with atrial fibrillation had PV anomalies and 3% had coexistence of 2 PV variants, indicating that PV variants are not rare.

Electroanatomical Correlation of Repolarization Abnormalities in Brugada Syndrome: Detection of Type 1 Electrocardiogram in the Right Ventricular Outflow Tract

To the Editor: ST-segment elevation is the most important characteristic for the diagnosis of Brugada syndrome (BrS). The Consensus Report of Brugada Syndrome defined type 1 electrocardiogram (ECG) (coved-type ST-segment elevation ≥0.2 mV with a negative T-wave in the right precordial lead) is

Aortic Stiffness Is an Independent Predictor of Left Ventricular Function in Patients with Coronary Heart Disease

Although aortic stiffness plays an important role in patients with coronary artery disease (CAD), the influence of aortic stiffness on left ventricular systolic function has not yet been fully evaluated. In the present study, we measured brachial-ankle pulse wave velocity (baPWV), which is a new index of aortic stiffness, in patients with CAD (CAD group, n = 170, 67 ± 9 years old) and without CAD (non-CAD group, n = 81, 63 ± 8 years old), and evaluated the relationship between baPWV and left ventricular systolic function in patients with CAD. baPWV in the CAD group was significantly higher than that in the non-CAD group (1,794 ± 350 vs. 1,469 ± 292 cm/s, p < 0.05), although both systolic and diastolic blood pressure were comparable between the two groups. In the CAD group, the baPWV was higher in patients with three-vessel disease than that in patients with one-vessel disease (1,885 ± 542 vs. 1,720 ± 373 cm/s, p < 0.05). In the CAD group, multivariate analysis demonstrated that baPWV and pulse pressure independently correlated with left ventricular ejection fraction (LVEF). In conclusion, in patients with CAD, baPWV, which is a simple marker of aortic stiffness, increases with CAD severity and correlates with left ventricular systolic function independent of CAD severity.

Abnormal restitution property of action potential duration and conduction delay in Brugada syndrome: both repolarization and depolarization abnormalities

AIMS 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). METHODS AND RESULTS 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). CONCLUSIONS 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.

Differential effects of cardiac sodium channel mutations on initiation of ventricular arrhythmias in patients with Brugada syndrome

BACKGROUND Premature ventricular contractions (PVCs) do not occur frequently but can induce ventricular fibrillation (VF) in patients with Brugada syndrome. The effect of SCN5A mutation on the onset of ventricular arrhythmias is unknown. OBJECTIVE The purpose of this study was to evaluate PVC morphology and onset of VF in patients with Brugada syndrome. METHODS Morphology of PVCs was evaluated by 12-lead ECG in 32 patients with Brugada syndrome. Patients had spontaneous ventricular arrhythmia (n = 17) or sodium channel blocker-induced ventricular arrhythmia (n = 19). Patients were classified into two groups according to the existence of SCN5A mutation (22 mutation negative, 10 mutation positive). RESULTS Patients without mutation often had PVCs of left bundle branch block (LBBB) morphology (82%), especially with inferior axis (77%). Patients with mutation had PVCs of both right bundle branch block (36%) and LBBB (64%) morphologies. Only two patients with mutation had PVCs of LBBB, inferior-axis morphology. CONCLUSION Patients without SCN5A mutation often had PVCs of LBBB, inferior-axis morphology, suggesting a right ventricular outflow tract origin. Patients with SCN5A mutations had PVCs that originated from both the right and left ventricles.

Abnormal transmural repolarization process in patients with Brugada syndrome

BACKGROUND 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. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS Loss of rate-dependent QT dynamics may be associated with occurrence of VF in BrS.

Calcification analysis by intravascular ultrasound to define a predictor of left circumflex narrowing after cross-over stenting for unprotected left main bifurcation lesions

OBJECTIVES The aim of this study was to identify predictors of significant LCx-ostium compromise after distal unprotected left main coronary artery (ULMCA) stenting on the basis of baseline intravascular ultrasound (IVUS). BACKGROUND Provisional single-stenting is considered as the default strategy for non-true bifurcation lesions in ULMCA. However, in certain cases, left circumflex artery (LCx)-ostium stenting is necessary. METHODS A total of 77 patients underwent percutaneous coronary intervention with drug-eluting stents for non-true bifurcation lesions in ULMCA and had IVUS evaluation. Pre-procedural IVUS was performed to measure cross-sectional areas at the following segments: left main trunk, left anterior descending artery (LAD)-ostium. Post-stenting-narrowing at the circumflex ostium (PSN-LCx) was defined as the presence of more than 50% diameter stenosis at the LCx-ostium as determined by quantitative coronary angiography analysis. RESULTS PSN-LCx occurred in 27 (35%) patients. The presence of calcified plaque at the culprit lesion as identified by IVUS was more frequently observed in the PSN-LCx group as compared to the non-PSN-LCx group (81.5% vs. 22.0%, p<0.001). Calcium arc in the PSN-LCx group was significantly greater than that in the non-PSN-LCx group (118.1°±69.9° vs. 36.9°±63.0°, p<0.001). On multivariable analysis, a calcium arc>60° was an independent predictor of PSN-LCx (odds ratio: 5.12, 95% confidence interval: 1.21-25.01, p=0.03). CONCLUSIONS The presence of calcified plaque at the culprit lesion appears to be one of the factors involved in LCx-ostial compromise in non-true bifurcation ULMCA lesions, especially when the calcium arc is >60°.

Acute Myocardial Infarction Caused by Left Main Coronary Artery Compression as a Result of a Mycotic Aneurysm of the Sinus of Valsalva.

An 83-year-old woman with a history of fever presented with severe chest pain progressing to cardiogenic shock. Her electrocardiogram showed evidence of anteroseptal myocardial infarction (MI). Urgent coronary angiography, with intra-aortic balloon pump support, indicated total occlusion of the left