Different effect of the pure Na+ channel-blocker pilsicainide on the ST-segment response in the right precordial leads in patients with normal left ventricular function.

BACKGROUND: The response of the ST-segment in the right precordial leads to Na+ channel blockers in patients without structural heart disease and a typical Brugada-type ECG has not been fully elucidated. METHODS AND RESULTS: A pilsicainide challenge test was performed in 161 patients and according to recently established ECG criteria and an organized computer algorithm, the ST morphology was classified and the maximum increase in the J wave amplitude (maxDeltaJ) from the standard and high right precordial leads V1-3 was examined. Before the test, subjects exhibiting type 1 ECG in the standard leads were excluded. After administering pilsicainide, type 1 ECGs in the standard leads were observed in 31 cases and a maxDeltaJ of >or=200 microV was observed in 29 cases (23 type 1, 2 type 2/3 and 4 normal ECGs). In the additional higher right precordial leads, type 1 ECGs were observed in 55 cases and a maxDeltaJ of >or=200 microV was observed in 45 cases (42 type 1 and 3 type 2/3 ECGs). CONCLUSIONS: A maxDeltaJ>or=200 microV induced by pilsicainide, including that measured in the high right precordial leads, was associated with a change mainly to a type 1 ECG.

Differentiation of the electrophysiological effects on the atrial myocardium between the pure Na channel blocker, pilsicainide, and flecainide.

UNLABELLED: The purpose of this study was to identify the difference between the pure Na channel blocker, pilsicainide and Ic-antiarrhythmic drug, flecainide, on the atrial electrophysiological characteristics. METHODS: The subjects consisted of 24 patients (48 +/- 12 years-old: P-group) in whom pilsicainide was administrated intravenously (1 mg/kg/10 min) and 31 patients (47 +/- 15 years-old: F-group) in whom flecainide was administrated intravenously (2 mg/kg/10 min). The atrial effective refractory period (ERP-A), intra-atrial conduction time (CT), max intra-atrial conduction delay (Max CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAZ) and intra-atrial conduction delay zone (CDZ) were measured before and after the drugs. RESULTS: Pilsicainide and flecainide significantly prolonged the ERP-A (211 +/- 27 msec to 246 +/- 39 msec; p < 0.001, 217 +/- 25 msec to 244 +/- 33 msec; p < 0.001, respectively) and CT (121 +/- 33 msec to 149 +/- 43 msec; p < 0.001, 122 +/- 22 msec to 153 +/- 27 msec; p < 0.001, respectively) to the same degree. However, the Max CD was shortened by pilsicainide, but not by flecainide. The RAFZ, FAZ and CDZ decreased in the P-group (21 +/- 25 msec to 4 +/- 10 msec; p < 0.01, 24 +/- 24 msec to 14 +/- 18 msec; p < 0.05, 56 +/- 29 msec to 43 +/- 32 msec, p < 0.05, respectively), but not in the F-group. CONCLUSIONS: The effects of atrial conduction delays may differ between pilsicainide and flecainide. Further examination will be needed to explain this mechanism.

Relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy.

We examined the relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy. Our results strongly indicate that cardiac sympathetic denervation and accelerated sympathetic nervous activity play important roles in the presence of microvolt-level T-wave alternans in patients with idiopathic-dilated cardiomyopathy.

Decrease in the spatial dispersion at the termination of atrial fibrillation by intravenous cibenzoline.

Atrial electrograms were recorded from the high right atrium, coronary sinus, and right lateral wall in 15 patients with induced atrial fibrillation (AF). Intravenous cibenzoline terminated AF in 8 patients (T group), but not in 7 patients (non-T group). The cycle length of the AF (AFCL) obtained by the autocorrelation function was measured every 5 s during the 30 s prior to the cibenzoline administration, and just before the termination of AF or at the end of the cibenzoline infusion in the non-T group. The mean AFCL, and spatial and temporal dispersion of the AFCL were then compared between the 2 groups (dispersion = standard deviation x 100 /mean AFCL). Cibenzoline significantly increased the mean AFCL and decreased the spatial dispersion in both groups. No significant difference in either the mean AFCL or temporal dispersion before or after cibenzoline was observed between the 2 groups. In addition, no significant difference in the spatial dispersion before the cibenzoline was observed, but the spatial dispersion after the cibenzoline was significantly smaller in the T group than in the non-T group. The mean AFCL, and the spatial and temporal dispersion before the cibenzoline did not predict the termination of AF. The decrease in the spatial dispersion may be the most important mechanism by which intravenous cibenzoline terminates AF.

New method of determining the atrial fibrillation cycle length during human atrial fibrillation.

INTRODUCTION: The aim of this study was to investigate the usefulness of the autocorrelation function (reversed fast Fourier transform analysis) in determining the atrial fibrillation cycle length (AFCL) during human atrial fibrillation (AF). METHODS AND RESULTS: From 30 episodes of atrial electrograms recorded for 30 seconds from the high right atrium during type I AF in 16 patients, the mean, 5th percentile (p5), and 95th percentile (p95) of the AFCLs were measured by using a computer-picked activation time. The peak, minimum, and maximum AFCLs also were measured by using the autocorrelation function. The mean AFCL was retrieved at the point of the maximum peak of the coefficient of the first positive autocorrelogram. The minimum AFCL (min AFCL) was chosen as the point where the first positive autocorrelogram crossed the baseline from negative to positive, and the maximum AFCL (max AFCL) was chosen as the point where the first positive autocorrelogram crossed the baseline from positive to negative. There was a significantly strong correlation between the mean and peak AFCLs (r = 0.995, P < 0.0001), p5 and min AFCLs (r = 0.953, P < 0.0001), and p95 and max AFCLs (r = 0.98, P < 0.0001). CONCLUSION: The autocorrelation function was useful in determining the AFCLs, at least during type I AF. The min AFCL may be used as an index of the refractory period during AF when the p5 AFCL approximates the refractory period.

Effects of flecainide on the electrophysiological properties of atrial vulnerability in humans.

The aims of this study were to evaluate the changes in the electrophysiological characteristics of the right atrium after the administration of flecainide and to clarify whether flecainide has a selective effect on human atrial tissue. Electrophysiological measurements were made in 38 patients, before and after intravenous administration of flecainide (2 mg/kg per 10 min). The effective refractory period of the right atrium (ERP-A), maximum conduction delay (Max.CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were studied in the patients who were divided into 2 groups based on whether repetitive atrial firing (RAF) was induced in the baseline study. Flecainide significantly prolonged the ERP-A (202+/-22 to 238+/-33 ms, p<0.001) and shortened Max.CD (77+/-17 to 63+/-32 ms, p<0.05) in the patients with RAF, but not in those without RAF in the baseline study. After flecainide administration, there were significant reductions in the RAFZ (43+/-22 to 13+/-19 ms, p<0.0001), FAAZ (51+/-22 to 28+/-26 ms, p<0.001) and CDZ (70+/-21 to 48+/-30 ms, p<0.01) in the patients with RAF. However, atrial fibrillation (AF) was induced by stimulation after flecainide in 2 patients without RAF in the baseline study. There was a significant negative correlation between the ERP-A in the baseline study and the change in the ERP-A upon flecainide administration (r=0.45, p<0.01). Flecainide may preferentially activate the substrate for AF and RAF, but that action is mainly based on the electrophysiological characteristics found in the baseline study.

Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm.

An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p <0.05) or controls (24.7 +/- 11.1, p <0.01). The relative expression level of Cx40 messenger ribonucleic acid was also significantly lower in MVD/AF patients (0.23 +/- 0.13) than in MVD/NSR patients (0.47 +/- 0.26, p <0.01) or controls (0.47 +/- 0.17, p <0.01). For Cx43 protein and messenger ribonucleic acid, there was no significant difference in relative expression levels among the 3 groups. Interestingly, the level of serine-phosphorylated Cx40 was approximately 52% greater in MVD/AF patients than in controls. In MVD/AF patients, the immunoreactive signal of Cx40 was significantly lower than in controls. There was no significant difference in the connective tissue-volume fraction among the groups. Thus, downregulation of Cx40 and abnormal phosphorylation of Cx40 may result in abnormal cell-to-cell communication and alteration in the electrophysiologic properties of the atrium, leading to the initiation and/or perpetuation of AF.

Beta-blocker decreases the increase in QT dispersion and transmural dispersion of repolarization induced by bepridil.

Bepridil is effective for intractable cardiac arrhythmia, but in rare cases will induce torsades de pointes (TdP) associated with QT interval prolongation. Beta-blockers will effectively prevent TdP in some clinical settings, so the effect of beta-blocker on the change in QT interval, QT dispersion and transmural dispersion of repolarization (TDR) induced by bepridil was investigated in 10 patients (7 male, 3 female; 62+/-6 years old) with intractable paroxysmal atrial fibrillation. The QTc interval, QTc dispersion and TDR were measured before and after 1 month of administration of bepridil, and then a beta-blocker was added and the QTc interval, QTc dispersion and TDR re-measured 1 month later. Bepridil significantly prolonged the QTc interval (0.42+/-0.05 to 0.50+/-0.08; p<0.01), and increased both the QT dispersion (0.07+/-0.05 to 0.14+/-0.08; p<0.01) and TDR (0.10+/-0.04 to 0.16+/-0.05; p<0.01). The addition of a beta-blocker decreased the QTc interval (0.50+/-0.08 to 0.47+/-0.04; p=0.09) and significantly decreased both the QTc dispersion (0.14 +/-0.08 to 0.06+/-0.02; p<0.01) and TDR (0.16+/-0.05 to 0.11+/-0.04; p<0.001). Compared with the control, the combination therapy significantly prolonged the QTc interval, but did not increase either QTc dispersion or TDR, and so was effective in all patients with intractable AF. The findings suggest that beta-blocker reduces the increase in QT dispersion and TDR induced by bepridil, and combined therapy with bepridil and beta-blocker might thus be useful for intractable atrial fibrillation.