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Aims: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. One of the reasons for discrepant results may be due to the selection of stimulation protocol. We evaluated the prognostic value of a positive PES result (PES+) according to the inducible pacing sites and the number of extra-stimuli in BrS patients without previous cardiac arrest (CA)., Methods and Results: We enrolled 224 consecutive BrS patients without previous CA (mean age 51 ± 14 years, 209 males), who underwent PES with the identical protocol. Clinical outcomes of development of CA were explored in the patients with and without PES+ according to sites and number of extra-stimuli. During a mean follow-up period of 76 months, 12 cardiac events (CE: sudden cardiac death or documented VF) occurred (8 with and 4 without PES+). The incidence of CE was not different in patients with and without PES+, those with PES+ from RVA (n = 72) or RVOT (n = 60), and those with and without PES+ by up to 2 extra-stimuli (n = 58). However, in patients that were PES+ by a single extra-stimulus (n = 8) the incidence of CE was significantly higher than in those without PES+ (8.8 vs. 0.6%/year, P < 0.0001). On univariate analysis, syncope, spontaneous type 1 ECG, and PES+ by a single extra-stimulus were associated with CE., Conclusion: Details of the stimulation protocol may be important for risk assessment in BrS patients without previous CA. A single extra-stimulus may be useful in stratifying risk in patients with spontaneous type 1 ECG and syncope.

We established a mass spectrometry-based quantitative method of assaying CD3ε, a component of the T-cell receptor complex. It revealed a CD3ε level of 1 mol per cell in a newly derived canine T-cell lymphoma cell line. Our results suggest that this method has sufficient sensitivity to quantify CD3ε levels in canine lymphoma cells reliably.

Background: The slit diaphragm (SD) is a complex of podocyte-specific proteins and plays a significant role in glomerular filtration. To understand podocyte biology, it is important to determine the expression amount of the SD complex proteins. This study aimed to quantify the absolute amount of nephrin, which is believed to be a major component of SD, in podocytes and to apply that method to normal and puromycin aminonucleoside (PAN) nephrosis rats., Methods: The counting method for podocyte number in a glomerulus was developed by three-dimensional reconstruction imaging of Wilms tumor (WT-1) immunofluorescence on isolated glomeruli. Absolute amount of nephrin was quantified by mass spectrometry using the selected reaction monitoring (SRM) mode with a stable isotope-labeled peptide., Results: The number of podocytes per glomerulus was 95.5±17.6 in the control rats, 90.7±19.2 on Day 4 and 90.7±26.2 on Day 7 in PAN nephrosis rats. The amount of nephrin per glomerulus in control rats was 1.02±0.11 fmol and those in PAN nephrosis rats were reduced to 0.46±0.06 fmol and 0.35±0.04 fmol on Day 4 and Day 7. The nephrin amount per podocyte was significantly decreased association with the development of proteinuria in PAN nephrosis rats., Conclusions: This study established the absolute quantification of nephrin and determined the amount of nephrin in a podocyte of normal and PAN nephrosis rat kidneys. This highly sensitive and selective quantification method for protein is a useful tool for the analysis of SD protein in a podocyte.

Aims: The atrioventricular (AV) septal junction includes the coronary sinus (CS) and the compact part of the AV node and its posterior extensions. It has been recognized as the target site for ablation therapy of the AV nodal reentrant tachycardia and its variant forms. Despite the clinical significance of this region, the arrangement of the musculature in the AV septal junction, including the CS, has not fully been elucidated. We tried to explore the histological muscular diversity within the AV septal junction., Methods and Results: Sixteen autopsied human hearts (seven women), mean age 59.8 years, without structural anomalies, were studied. We removed the whole AV septum, including the CS opening after the macroscopic measurements, and prepared serial sections parallel to mitral and tricuspid annuli (short-axis style) to elucidate the positional relationships between the compact AV node and the CS musculature. Out of 16 hearts, the CS musculature extended deeply into the AV septal junction in eight hearts. In the other eight hearts, the CS musculature was located above the AV septal junction. In the former group, we found that the offset of both annuli was wide (mean 3.8 +/- 1.4 vs. 2.4 +/- 1.1 mm), the distance between CS opening and membranous septum was long (mean 14.8 +/- 1.6 vs. 12.3 +/- 2.2 mm), and the CS opening level was lower and closer to the His bundle level (mean 2.8 +/- 1.9 vs. 5.8 +/- 2.9 mm) (P < 0.05)., Conclusion: The deep extension of CS musculature into the AV septal junction seems to increase the tissue non-uniformity in this area.

A 68-year-old woman with idiopathic dilated cardiomyopathy suffered from drug-resistant monomorphic ventricular tachycardia (VT). Electrophysiological study revealed a re-entrant VT circuit located just beneath the inferior mitral valve annulus. The VT was considered to be related to the mitral valve isthmus and was abolished by radiofrequency ablation. The patient died 2 years after the ablation due to worsening of heart failure and an autopsy was performed. Pathological examination revealed ablation scar tissue on the localized myocardial bundle running parallel to the mitral valve annulus. Therefore, this bundle appeared to comprise the slow conduction area of the re-entrant VT in this case.

Aims: To examine the initiating mode of Torsade de Pointes (TdP) in patients with congenital long QT syndrome (LQTS)., Methods and Results: We evaluated 111 episodes of TdP recorded on the electrocardiograms of 24 patients with congenital LQTS, and clarified the initiating mode, the three consecutive preceding RR intervals defined as C(2), C(1), and C(0), the timing of initiating premature ventricular contraction (PVC) and the cycle length (CL) of TdP. Three different initiating patterns were observed: (1) a "short-long-short" sequence (SLS) pattern (23 patients, 72 TdP, 65%) defined as one or more short-long cardiac cycles followed by an initiating short-coupled PVC (C(1)>C(2) and C(0)), (2) an "increased sinus rate" (ISR) pattern (8 patients, 28 TdP, 25%) defined as a gradual increase in sinus rate with or without T-wave alternans (C(2)>/=C(1)>/=C(0)), and (3) a "changed depolarization" (CD) pattern (5 patients, 11 TdP, 10%) defined as a sudden long-coupled PVC or fusion beat followed by short-coupled PVC. The C(0) was shorter in ISR than SLS and CD (mean C(0): 488 vs. 587 and 603 ms, respectively; P<0.05). Therefore, the initiating PVC appeared near the T-wave peak of the last beat before onset in ISR, while it occurred after the T-wave peak in SLS and CD. The CL of TdP was shorter in ISR than in SLS (256 vs. 295 ms, P<0.05)., Conclusions: Our data show the existence of three predominant initiating modes of TdP in patients with congenital LQTS and suggests a differential mechanism of initiation of TdP for each mode.

Aims: Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome., Methods and Results: We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477+/-42 to 631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39 ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms; P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%, controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state., Conclusion: Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes., (Copyright 2002 The European Society of Cardiology.)

Aims: This study was designed to determine, using electron-beam CT, whether there are morphological abnormalities in patients with the Brugada syndrome and to elucidate the relationship between those abnormalities and arrhythmogenesis., Methods and Results: Twenty-six consecutive patients with the Brugada syndrome and 23 age- and gender-matched control subjects (controls) were evaluated for morphological abnormalities using electron beam CT. Electron beam CT demonstrated morphological abnormalities of the right ventricle in 21 (81%) of 26 patients, but in only two (9%) of 23 controls. The sites of morphological abnormalities were the right ventricular outflow tract area in 17 patients and the inferior wall of the right ventricle in four patients. Of the seven patients with monoform premature ventricular contractions recorded only in the acute phase, four of the five patients with premature ventricular contractions from the right ventricular outflow tract area had morphological abnormalities in the right ventricular outflow tract area, and the other two patients with premature ventricular contractions from the inferior wall of the right ventricle had morphological abnormalities in the inferior wall of the right ventricle., Conclusion: The sites of morphological abnormalities detected by electron beam CT in patients with the Brugada syndrome were related to the origins of premature ventricular contractions recorded only in the acute phase, which may trigger ventricular fibrillation. These morphological abnormalities may be related to arrhythmogenic substrates in patients with the Brugada syndrome.

Aims: Brugada syndrome is considered to be a distinctive subgroup of idiopathic ventricular fibrillation. Identification of the circadian pattern of ventricular fibrillation would contribute to the elucidation of its underlying pathophysiology, but this pattern remains unknown in patients with Brugada syndrome., Methods: and Results A total of 12 consecutive Brugada syndrome patients (46+/-14 years, all male) who underwent implantation of an implantable cardioverter defibrillator were studied. The distribution of the time of ventricular fibrillation detection was examined and classified into four 6-hour time periods of the day. The mean follow-up period following implantation was 777+/-535 days. In six out of the 12 patients, ventricular fibrillation occurred during follow-up. The data logs revealed that ventricular fibrillation was detected 30 times (range, 3-9). Ventricular fibrillation was observed more frequently at night ( 1800 h to 0600 h) than in the day (0600 h to 1800 h) (93.3% [28/30] vs 6.7%[2/30], P<0.001), and during sleep than while awake (86.7% [26/30] vs 13.3%[4/30], P<0.001). Ventricular fibrillation occurred most frequently between midnight and 0600 h in patients with ventricular fibrillation episodes during sleep (76.9% [20/26] vs 23.1%[6/26], P<0.01)., Conclusion: These results suggest that increased nocturnal vagal activity and withdrawal sympathetic activity may play an important role in the arrhythmogenesis of the Brugada syndrome.

Diaphragmatic tumors, whether benign or malignant, may not generally reveal any symptoms in the early phase and may be found accidentally. During a pre-employment physical examination, a 20-year-old woman was found to have an abnormal shadow on the left diaphragm. An X-ray film, computed tomography and ultrasonography showed a giant mass on the left side, to the rear of the heart. She underwent surgery via a left thoraco-abdominal approach. The lesion was found to arise from the left diaphragm, and multiple disseminated lesions were scattered in the left thoracic cavity. Histological examination showed many large, oxyphilic rhabdoid cells between diffusely proliferating, spindle-shaped cells, and the tumor was subsequently diagnosed as a pleomorphic rhabdomyosarcoma of the diaphragm, of which the location and histological type were very rare. Despite adjuvant therapy, chest X-ray and CT revealed increasing tumor growth in the left cavity and she died one year after surgery.

Abnormal repolarization associated with torsades de pointes is expressed as QT prolongation. The physiological response to class Ia antiarrhythmic drugs is also reflected in prolongation of the QT interval. However, the essential difference between pathological and physiological prolongation is not clear. The purpose of this investigation was to differentiate between pathological and physiological changes in the repolarization waves of surface electrocardiograms (ECG) induced by class Ia drugs. In 18 patients without a history of torsades de pointes or syncope (control group), TU waves were compared before and after the administration of class Ia drugs (physiological response). In eight patients with torsades de pointes induced by class Ia drugs (torsades de pointes group), the TU waves at torsades de pointes were compared with those before drug administration (pathological response). In the control group, although the QTc (measured in lead II and corrected for heart rate by Bazett's formula) was increased significantly (0.40 +/- 0.04 to 0.44 +/- 0.05 s, P < 0.001), the U-amp (amplitude of the U wave measured in a precordial lead where the T and U waves were clearly differentiated) remained unchanged. In the torsades de pointes group, however, the QTc was increased (0.42 +/- 0.04 to 0.54 +/- 0.07 s, P < 0.02); the U-amp was also increased, significantly (0.09 +/- 0.07 to 0.27 +/- 0.18 mV, P < 0.05). Thus, enlargement of the U wave may help to differentiate between the physiological and pathological responses to class Ia drugs.

In order to evaluate the electrophysiological effects of the combined administration of disopyramide and mexiletine on anterograde accessory pathway conduction, we studied 11 patients with Wolff-Parkinson-White (WPW) syndrome. Disopyramide was first infused intravenously at 1 mg kg-1 for 5 min followed by a continuous infusion at 0.025 mg kg-1 min-1. After the infusion rate of disopyramide was decreased to 0.004 mg kg-1 min-1 to maintain a lower serum concentration, mexiletine was infused at 2 mg kg-1 for 5 min followed by a continuous infusion at 0.008 mg kg-1 min-1 (protocol 1). The shortest atrial paced cycle length with 1:1 anterograde accessory pathway conduction (shortest CL with 1:1) and the anterograde effective refractory period of the accessory pathway (ERP) were measured: (1) before drug administration, (2) after disopyramide was given alone, and (3) after disopyramide and mexiletine were combined at lower concentrations. The same protocol was repeated with the order of drug administration reversed (mexiletine followed by disopyramide) in all patients (protocol 2). Both disopyramide and mexiletine lengthened the shortest CL with 1:1 and the ERP to the same degree. The combination of disopyramide and mexiletine at lower concentrations further lengthened the shortest CL with 1:1. It was longer than with disopyramide (protocol 1) or mexiletine (protocol 2) alone [protocol 1: 412 +/- 169 ms (combination) vs 356 +/- 117 ms (disopyramide); P less than 0.05, protocol 2: 409 +/- 166 ms (combination) vs 355 +/- 119 ms (mexiletine); P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)