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

rugada syndrome is characterized by a ST-segment elevation in the right precordial leads and associated with sudden cardiac death secondary to rapid polymorphic ventricular tachycardia or ventricular fibrillation. 1 A recent consensus report proposed 3 types of ST-segment elevation (types 1 to 3) and indicated that a coved-type ST-segment elevation >0.2 mV (type 1 electrocardiogram (ECG)), in the presence or absence of Na channel blockers, is necessary for diagnosis of this syndrome. 2,3 Individuals with saddle-back type ST-segment elevation in the right precordial leads (SB-ECG), which applies to type 2 or 3 ECG, are much more prevalent than those with type 1 ECG, 4 at a rate of 58/10,000 inhabitants in Japan. 5 Although previous reports show asymptomatic individuals with SB-ECG who exhibit a type 1 ECG under drug administration are low risk for fatal cardiac event for middle-term periods, 6,7 long-term prognosis in those individuals is still unclear. For individuals with SB-ECG, therefore, a drug provocation test using Na channel blockers is necessary and generally considered helpful to diagnose a type 1 ECG. 6,8,9 In some cases, the drug testing is accompanied with the risk of drug-induced ventricular tachyarrhythmias. 3,10 It is difficult to undergo drug provocation testing for all individuals with SB-ECG because of the high prevalence. Although the differences between baseline ECG parameters of positive responders (PR) and negative responders (NR) on the drug testing have been reported, [11][12][13] it remains unclear which parameters on baseline ECG are clinically useful as predictors of test outcome. However, it has been reported that the ECG recorded at higher intercostal space is more sensitive and useful for diagnosis of Brugada syndrome than that recorded at the standard position. [14][15][16][17][18][19] In the present study, to avoid the risk of drug-induced ventricular tachyarrhythmias on drug testing, we analyzed baseline ECG parameters recorded at the standard position and the third intercostal space in individuals with SB-ECG, and evaluated predictors of PR on drug provocation testing. MethodsIn a total of 62 consecutive individuals with SB-ECG, we performed the drug provocation test using pilsicainide, a class Ic pure Na channel blocker, between September 2002 and December 2007. In these individuals, SB-ECG in leads V1 and V2 was exhibited in 4 and 58 individuals, respectively. In this study, we enrolled 58 individuals (55 males, mean age 51±11 years) with SB-ECG in lead V2. Of the 58 individuals, 48 individuals showed SB-ECG in lead V2 at the third intercostals space (V2IC3). The remaining 10 individuals did not show type 1 ECG in lead V2IC3. Patients who had exhibited a diagnostic ECG (type 1 ECG) at any Conclusions:In individuals with SB-ECG, DR20 and DR20-STb in leads V2 and V2IC3 might be useful

Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

A Predictor of Positive Drug Provocation Testing in Individuals With Saddle-Back Type ST-Segment Elevation

Shimeno

Takagi

Maeda

et al. 2009

“…If we performed a provocation test for BS patients before and after MCG recording, it might be possible to present more data about the changes according to the different types of BS ECG changes. 18 To study the MCG findings of BS patients with minimal clinical manifestation will be needed to show the additional role of MCG in the diagnosis of BS patients.…”

Section: Study Limitationsmentioning

confidence: 99%

Magnetic Dispersion of the Late Repolarization in Brugada Syndrome

Joung

Kim

Lee

et al. 2008

Background Magnetocardiography (MCG) is a new noninvasive modality for recording cardiac depolarization and repolarization and was used in the present study to evaluate abnormalities in patients with Brugada syndrome (BS). Methods and ResultsThe MCG findings of 10 BS, 21 right bundle branch block (RBBB), and 34 normal patients were compared. On the horizontal spatiotemporal activation graph (STAG), the r' waves were more frequently located on the right side in the RBBB than in the normal (p=0.001) or BS groups (p=0.001). The maximum current angles of the r' wave fell into the northwest axis in all BS patients as compared to having a right axis deviation in 19 of 21 RBBB patients (90.4%, p=0.001). In the magnetic field and current density vector maps during late repolarization, the BS group had a non-dipole pattern more frequently and a higher number of poles compared with the normal (p=0.001) and RBBB groups (p=0.001). Conclusions During depolarization, the horizontal STAG location and maximum current angle of the r' wave were beneficial in differentiating BS from RBBB and normal. The magnetic dispersion was a more frequently observed finding in BS patients than in RBBB and normal patients during late repolarization. (Circ J 2008; 72: 94 -101)

“…1 Pharmacological Na channel blockade exaggerates or unveils the ST-segment elevation. 2 Programmed electrical stimulation can induce VF, and the His-ventricular (HV) conduction time is prolonged. [3][4][5] The findings are compatible with the abnormality of the cardiac Na channel, and in ~20% of patients with this syndrome, Chen et al found several mutations in the SCN5A that encodes the α-subunit of the voltage-gated cardiac Na channel.…”

mentioning

confidence: 99%

Dynamic Change in ST-Segment and Spontaneous Occurrence of Ventricular Fibrillation in Brugada Syndrome With a Novel Nonsense Mutation in the SCN5A Gene During Long-Term Follow-up

Kawamura

Ozawa

Yao

et al. 2009

A 67-year-old male underwent genetic testing under the diagnosis of Brugada syndrome because of recurrent ventricular fibrillation with coincident ST-segment elevation in either right precordial, inferior leads or both since the age of 55 years. Screening of gene mutations using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing identified a novel nonsense mutation (R179X) of SCN5A in a heterozygous manner. The functional assay for the identified mutation, using a whole-cell patch clamp in the heterologous expression system, revealed that the nonsense mutation, located in the second transmembrane segment of the first domain (DI-S2) of the α-subunit, failed to synthesize the complete structure of the cardiac sodium channel, thus causing the non-functional channel. Coding effects by the gene mutation was altered during the 12-year follow-up, which might affect the clinical features of the patient through the ion channel density in the ventricle, dynamics of repolarization abnormality and conduction disturbance. (Circ J 2009; 73: 584 -588)