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.

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.

Reversible ventricular dysfunction (takotsubo cardiomyopathy) following polymorphic ventricular tachycardia.

A 67-year-old female with recurrent syncope and no obvious heart disease developed ventricular dysfunction, known as takotsubo cardiomyopathy, following a 90 s episode of polymorphic ventricular tachycardia originating from a ventricular extrasystole with a short coupling interval. Cardiac catheterization performed 30 min after the arrhythmic event revealed angiographically normal coronary arteries, and left ventricular apical akinesis and basal hyperkinesis. An intracoronary injection of acetylcholine revealed no inducible coronary spasm, and an electrophysiological study revealed normal atrioventricular conduction and no inducible ventricular arrhythmia. Thirty hours after the arrhythmic event, electrocardiography revealed deeply inverted T waves in leads V3 to V6, I, and aVL, which continued for more than a week. Although no treatment was given to maintain hemodynamic stability, echocardiography revealed normal left ventricular contraction 14 days after the onset of the ventricular dysfunction. The reversible ventricular dysfunction might have been induced by altered catecholamine dynamics due to the persistent syncope during the occurrence of tachycardia.

Efficacy of steroid therapy for pacing failure in a patient with chronic myocarditis.

A 66-year-old man had a progressive increase in the pacing threshold over a one-year period, resulting from chronic myocarditis. Following steroid therapy, the pacing threshold decreased and became stabilized, and was accompanied by a decrease in the serum creatine kinase, cardiac myosin light chains and pro-collagen III peptide values, but cardiac function did not improve. Endocardial biopsy showed that there was no progression in the fibrosis. The pacing failure improved, but the cardiac function did not. It was believed that the steroid therapy suppressed the progression of the inflammation and fibrosis caused by the chronic myocarditis.

Discrimination of Brugada syndrome patients from individuals with the saddle-back type ST-segment elevation using a marker of the standard 12-lead electrocardiography.

BACKGROUND: In the clinical situation, the saddle-back (S-B) type is more frequently detected than the coved type. In the present study, the discrimination of Brugada syndrome from the S-B type individuals using a marker of the standard 12-lead electrocardiography (ECG) was attempted. METHODS AND RESULTS: The study group consisted of 55 individuals with the S-B type in whom pilsicainide provocation test (PLC test) was carried out. The time from the onset of the QRS wave in lead V(2) (IV (2)) to the peak of the late R-like wave in the QRS wave (PV(2)), and the time from IV(2) to the offset of the QRS wave in lead V(5) (EV(5)) were measured. The coved type was induced by the PLC test in 29 cases (N-C group), but not in the remaining 26 cases (N-N group). The (IV(2) -PV(2)) - (IV(2) - EV(5)) value before the PLS test was greater in the N-C group than in the N-N group. The negative predictive value of ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' was 76.4% for the prediction of a positive PLC test. CONCLUSIONS: A ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' is a useful ECG marker for the discrimination of Brugada syndrome in the S-B type individuals.

Automated detection of Brugada-type electrocardiogram using diagnostic criteria of the European Society of Cardiology and the American Heart Association.

The diagnostic criteria of Brugada syndrome were reported from the European Society of Cardiology (ESC) and the American Heart Association in 2002. We examined the automated detection of Brugada-type electrocardiogram (ECG) on 12-lead ECG analysis program by modifying ESC criteria and evaluated it. In ESC criteria, Brugada-type ECG was classified into 3 types of ST-segment abnormalities of V1 to V3 leads. We modified these criteria and determined automated detection criteria as follows: type 1: STj>or=0.2 mV and STj>ST1>ST2 and T<0 mV; type 2: STj>or=0.2 mV and STj>STmin>or=0.1 mV and T>0 mV and T<1.8xR' and Sor=0.2 mV and 0.1 mV>STmin>0 mV and T>0 mV and T<1.8xR' and S>or=3.0 mV; STj, ST1, and ST2 are amplitude of the ST segment (STj: J point, ST1: J point +40 milliseconds, ST2: J point +80 milliseconds). We evaluated these criteria with 97 ECGs from 27 patients, which are diagnosed as Brugada syndrome in university hospital. Brugada-type ECGs were detected correctly in 85 of total 97 ECGs (sensitivity, 88.7%, type 1: 32/32, type 2: 50/61, type 3: 4/4). As compared with 5 cardiologists interpretation of Brugada-type ECGs, computer classified incorrectly in 20 ECGs (type 1: 2, type 2: 17, type 3: 1) in 21,524 cases.

Brugada syndrome-like ST-segment elevation increase exacerbated by vomiting.

The patient was a 53 year-old male who had 3 syncopal episodes over a 6-month period. In the electrophysiological study, ventricular fibrillation (VF) was repeatedly induced by the ventricular extrastimulus method. Intravenous pilsicainide was administered, and the J-point and ST-segment in the right precordial leads became slightly elevated just following drug administration. Five min later, the patient experienced severe nausea and then vomited twice, at which point the electrocardiogram (ECG) showed increased elevation of the J-point and ST-segment. These ECG changes recovered to normal 30 min later. The cause of his syncope was strongly suspected to be related to the VF associated with Brugada syndrome. An interesting aspect of this case was the particular type of J-point and ST-segment elevation that was induced when the patient experienced nausea and vomiting. It is proposed that this phenomenon originated from the vagal stimulation associated with the nausea and vomiting.

Autonomic imbalance as a property of symptomatic Brugada syndrome.

The autonomic properties in 27 patients with the electrocardiographic morphology of Brugada syndrome were investigated using 24-h Holter monitoring: 10 patients had a history of ventricular fibrillation (VF; Br-VF group) and 17 did not (Br-N group); there were 26 healthy subjects enrolled in this study. All subjects underwent normal Holter data monitoring and power spectral analysis. Few extrasystoles were observed in either group, and the mean heart rate (HR), maximum HR, and total heart beats over 24 h were obtained. All of these measurements were significantly lower in the Br-VF group than in the Br-N and healthy subject groups. The RR interval variability was analyzed over 512 beats every 10 min. The high-frequency component (0.15-0.40 Hz; HF), low-frequency component (0.04-0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. The HF was significantly higher and LF/HF ratio lower in the Br-VF group than in the healthy subjects. The HF was also significantly higher than in the Br-N group. During the night (00.00-05.00 h), the HF was significantly higher in the Br-VF group, and the LH/HF lower. During the day (12.00-17.00 h), the HF was significantly higher in the Br-VF group, but there was no difference in the LF/HF. These results indicate that high vagal tone and low sympathetic tone are specific properties of symptomatic Brugada syndrome.

Clinical significance of electrocardiography recordings from a higher intercostal space for detection of the brugada sign.

BACKGROUND: The significance of higher intercostal space electrocardiography (HICS ECG) for the detection of the Brugada sign was investigated. METHODS AND RESULTS: The subjects consisted of 113 cases (108 males, 5 females; mean age, 57+/-17 years) with incomplete right bundle branch block type QRS morphology and ST-segment elevation (>0.10 mV) in the right precordial leads. Obvious structural heart disease was not observed in any of the subjects. The V(1-3) leads of the standard 12-lead ECG and the HICS ECG were recorded in the supine position, and the amplitude of the terminal portion of the QRS (J-point) and ST-segment (80 ms from the J-point) were measured. In the HICS ECG, there was an increase in the area in which the Brugada sign was detectable (47 leads to 66 leads), and in cases with the Brugada sign, the amplitude of the J-point increased. CONCLUSIONS: The HICS ECG may be helpful for the detection of the Brugada sign.

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.

Experimental study on the effectiveness and safety of radiofrequency catheter ablation with the cooled ablation system.

Experimental in vitro and in vivo studies were performed to assess the effectiveness and safety of the cooled-tip catheter and the Cooled Ablation System, which enables the creation of deeper and wider burn lesions in the myocardial tissue using radiofrequency current. This system was confirmed to consistently create large burns by cooling the catheter tip with circulating water within the catheter, even under unfavorable conditions. On the other hand, unfavorable effects, as a result of over burning, such as explosive vaporization within the tissue (the 'pop' phenomenon), tissue carbonization, coronary artery injury and lung injury were identified. 'Pop' was difficult to predict, but it is important to know how it can be avoided. No 'Pop' was seen without first observing an impedance decrease, thus it was considered safe to decrease the radiofrequency current if the impedance began to decrease. This system will be very effective for ablation of refractory arrhythmias, such as ventricular tachycardia or atrial flutter, but it is recommended that only experienced electrophysiologists use this system to avoid serious complications.