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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.

We report a patient with a concealed type of Brugada syndrome. The electrocardiogram in the emergency department revealed atrial fibrillation with an almost normal ST segment. Slight electrocardiogram abnormalities of the J wave and mild ST-segment elevation appeared in the inferolateral leads a few days later. Although the ST segment in the right precordial leads, including that recorded from the high intercostal space recording sites, was completely normal, a drug challenge test using pilsicainide revealed a coved-type ST-segment elevation only in a modified V2 lead placed 1 or 2 intercostal spaces higher.

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.

Background: Telethonin (TCAP) is a Z‐disk protein that maintains cytoskeletal integrity and various signaling pathways in cardiomyocytes. TCAP is shown to modulate α‐subunit of the human cardiac sodium channel (hNav1.5) by direct interactions. Several TCAP variants are found in cardiomyopathies. We sought to investigate whether TCAP variants are associated with arrhythmia syndromes. Methods: Mutational analyses for TCAP were performed in 303 Japanese patients with Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and J‐wave pattern ECG. Using patch‐clamp techniques, electrophysiological characteristics of hNav1.5 were studied in HEK‐293 cells stably expressing hNav1.5 and transiently transfected with wild‐type (WT) or variant TCAP. Results: We identified two TCAP variants, c.145G>A:p.E49K and c.458G>A:p.R153H, in four individuals. p.E49K was found in two patients with ARVC or BrS. p.R153H was found in two patients with BrS or J‐wave pattern ECG. No patient had variant hNav1.5. Patch‐clamp experiments demonstrated that peak sodium currents were significantly reduced in cells expressing p.R153H and p.E49K compared with WT‐TCAP (66%, p.R153H; 72%, p.E49K). Voltage dependency of peak IV curve was rightward‐shifted by 5 mV in cells expressing p.E49K compared with WT‐TCAP. Voltage dependency of activation was not leftward‐shifted by p.R153H, while voltage dependency of steady‐state inactivation was leftward‐shifted by p.E49K. Conclusions: We found two TCAP variants in the patients with BrS, J‐wave pattern ECG, and ARVC that can cause loss‐of‐function of the hNav1.5 in heterologous expression systems. Our observation suggests that these variants might impair INa and be associated with the patients' electrophysiological phenotypes. Further studies linking our experimental data to clinical phenotypes are warranted. [ABSTRACT FROM AUTHOR]

Background: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. Objective: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. Methods: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study. Genetic screening using direct sequencing identified a novel SCN5A variant, p.V1328M. Electrophysiological parameters of WT and p.V1328M and their effects on drug pharmacokinetics were studied using the patch-clamp method. Results: Whole-cell sodium current densities were similar for WT and p.V1328M channels. While p.V1328M mutation did not affect the voltage-dependence of the activation kinetics, it caused a positive shift of voltage-dependent steady-state inactivation by 7 mV. The tonic block in the presence of pilsicainide was similar in WT and p.V1328M, when sodium currents were induced by a low frequency pulse protocol (q15s). On the contrary, p.V1328M mutation enhanced pilsicainide induced use-dependent block at 2 Hz. (Ki: WT, 35.8 μM; V1328M, 19.3 μM). Conclusion: Our study suggests that a subclinical SCN5A mutation, p.V1328M, might predispose individuals harboring it to drug-induced Brugada Syndrome. [ABSTRACT FROM AUTHOR]

Objective: Conduction velocity around the tricuspid valve annulus (TA. during typical atrial flutter (AFL. has been shown to be slowest in the inferior vena cava-tricuspid valve (IVC-TV. isthmus when compared to the septal or free wall segments of the TA. We investigated the conduction velocity in IVC-TV isthmus, dividing into three areas. Methods: We evaluated conduction velocity around the TA during typical AFL in 10 patients, using an electro-anatomic mapping system (CARTO™). Conduction velocity was calculated at six areas around the TA including the septal wall, upper wall, lateral wall, and isthmus wall, which was further divided into three areas, lateral isthmus, mid isthmus, and septal isthmus. Results: Conduction velocity around the TA during typical AFL was slowest in the IVC-TV isthmus. Further, conduction velocities (m/sec. in the mid isthmus (0.44±0.17. and septal isthmus (0.45±0.22. were significantly slower (p < 0.05. than that in the upper wall (0.67±0.26). Conclusions: The relatively slower conduction in IVC-TV isthmus resulted from the relatively slower conduction in the area from mid to septal isthmus. [Copyright &y& Elsevier]