Ryoji Kishi

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome: A Japanese Multicenter Registry

Background: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. Methods: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. Results: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (–), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (–): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001). Conclusions: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

Influence of Mobile Magnetic Resonance Imaging on Implanted Pacemakers

KISHI, R., et al.: Influence of Mobile Magnetic Resonance Imaging on Implanted Pacemakers. Purpose: Mobile magnetic resonance imaging (MRI) systems will be widely used in Japan. When traveling, mobile MRI generate alternating electromagnetic waves which may cause electromagnetic interference (EMI). This study was designed to determine whether this may influence the function of implanted pacemakers (PM). Methods and Results: The influence of the static magnetic fields was tested in the first method using a PM‐human model (Phantom). Magnetic force was simultaneously measured. The PM was switched to the magnet mode within 90 cm from the vehicle, where the magnetic force was = 2 mT. In the second method, six phantoms were placed on the side of the road, facing in three different directions in X‐Y‐Z axis orientations, at 1.3 m and 2.0 m above the ground. The mobile MRI passed by at a distance of 1 m from the phantoms at the speed of 20 or 40 km/h. In these experiments, magnet mode switch of the PM was observed for 2 seconds when the vehicle passed close to the phantoms, though no electrical noise was recorded. Conclusion: Mobile MRI vehicles can switch a PM to magnet mode when the distance between patient and vehicle is <90 cm, regardless of whether the vehicle is moving or at a stop. Patients with implanted PM should not approach within <1 m of a mobile MRI. No other EMI‐induced PM dysfunction was detected. (PACE 2003; 26[Pt. II]:527–529)

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel—blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed‐effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS‐like elevation of ST‐segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight‐normalized systemic clearance of pilsicainide. Patients who showed a BrS‐like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His‐Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug‐induced BrS‐like ECG morphology may be associated with augmented ECG responses to pilsicainide.

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome

Background: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. Methods: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. Results: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (–), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (–): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001). Conclusions: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

Lead Extractions are not Necessarily Required in the Treatment of Cases with Local Complications Unproven Resional/systemic Infection at the Pacemaker/implantable Cardioverter Defibrillator (ICD) Site

Introduction: In a case of pacemaker and/or implantable cardioverter defibrillator (ICD) implantations, there is the possibility of infections related to the device. In such case, the removal of the total system is desirable, however, the lead extraction can sometimes be difficult. Methods: Among 756 subjects who underwent a device implantation procedure, we experienced 19 cases with a device infection or skin problems requiring a surgical procedure such as thinning or inflammation of the skin over the pocket or lead. We divided these 19 cases into three groups as cases with neither systemic nor local infections (N group), cases with regional but systemic infections (R group), and cases with systemic infections (S group). And the prognoses of these cases were investigated. Results: Out of the 19 cases, 12 cases were classified into N group, 5 cases were classified into R group, and the remaining 2 cases were classified into S group. The lead extractions were performed in one case each in the N, R and S groups. None of the cases in the N group developed a systemic infection over an average observation period of 31 months. Four cases in the R group remain been free from systemic infection over an average observation period of 39.5 months. Conclusion: Lead extractions are the ideal treatment in cases with device implantation site complications, but are not necessary if the extraction is difficult.

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada SyndromeClinical Perspective : A Japanese Multicenter Registry

Background: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. Methods: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. Results: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (–), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (–): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001). Conclusions: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.