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Background Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. Methods and results Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63+/-12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66+/-11% and 40+/-6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. Conclusion Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients.

A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance. We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day. No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration. This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.

洞機能不全症候群 (SSS) における, 右心房有効不応期 (RA-ERP) のdispersion (ERPD) を検討した.対象はSSS32例 (平均年齢: 71歳, 男性: 12例, 女性20例) で, このうち15例 (47%) は発作性心房細動 (AF) を伴った徐脈頻脈症候群であった.洞機能障害やAFを伴わない房室プロック (AVB) 31例 (平均年齢: 77歳, 男性: 15例, 女性16例) を対照に, 心房期外刺激法を用いRA-ERPを, 高位, 中位, 低位の側壁および中隔の6点にて測定した.ERPD (最長ERP-最短ERP) は, SSS例78±38msec、AVB例45±22msecでSSS例において有意に大きかった (p

クラスI群薬無効の心房細動 (AF) 78例・心房粗動 (AFL) 23例, 計101例 (平均年齢61歳, 男性78例) に対するベプリジルの効果, 心電図変化および副作用をretrospectiveに検討した.持続性AFでは37例中17例 (45.9%) で, ベプリジル開始平均2.4カ月後に洞調律に復し, そのうち16例で洞調律が維持された (平均観察期間8, 5カ月) .発作性AFでは38例中32例 (84.2%) で平均観察期間8.2カ月間, 洞調律が維持された, 持続性AFLでは7例全例でベプリジル開始平均2.1ヵ月後, 洞調律へ復帰し, その全例で平均観察期間22.6カ月間, 洞調律が維持された.発作性AFLでは, 15例中12例 (80%) で洞調律が維持された (平均観察期間17.1ヵ月) .また, 電気的除細・粗動で洞調律に復した持続性AF9例中6例 (67.6%) で洞調律が維持された (観察期間平均10.5カ月) .2度以上の房室プロックの出現はなく, P拍数は68.2±10.9から60.0±9.0/分 (p

Background: Signal-averaged electrocardiograms (SAE) have mainly been studied in high risk patients with ischemic heart disease. A systemic study of the normal values and the comparative results using analytical methods has not been reported. Methods: We recorded SAE results in 200 apparently healthy subjects (100 males and 100 females, average age 28.9 years). The obtained signals were analyzed by for the time-domain (TD), frequencydomain (fast Fourier transform [FFT]), and spectral turbulence (ST) analyses. The normal values for these parameters, including differences according to gender, were evaluated. The correlation between body characteristics and individual measurements was also evaluated for each analytical method. Results were compared using previously reported criteria and gender-specific criteria. Results: The normal values for TD and FFT analyses, but not ST analysis, showed differences related to gender. A significant correlation was observed between the body characteristics noted in the TD and the FFT analyses, but this correlation was not seen for all parameters in the ST analysis. According to the conventional criteria, the rate of positive diagnosis was 9% for TD analysis, 4.5% for FFT analysis, and 2% for ST analysis. When gender-specific criteria were applied, it was 1% for TD analysis, 3.5% for FFT analysis, and 0.5% for ST analysis. However, the positive results for subjects that were found using TD analysis were discordant with the results found using FFT and ST analyses in those subjects. Conclusions: The normal values for TD and FFT analyses showed gender-related differences that were not seen using ST analysis. Gender-specific criteria are recommended when using TD analysis because it decreased positive results for healthy subjects. However, as discordant results were obtained among the various analyses, the selection of the method for analyzing the SAE and interpretation of the results should be performed with caution.

失神発作時にST上昇を伴った頸動脈洞症候群の2例を経験した.症例1は73歳男性, 頸部伸展時に洞徐脈から接合部調律となり, 血圧低下が出現, その後心電図上II, III, aVFでST上昇を認めた.硫酸アトロピンおよびジソピラミド静注で発作は改善し, DDDペースメーカーとジソピラミドの内服で失神発作は予防されていたが, 胸部大動脈瘤を合併しており, 1カ月後に突然死した.症例2は83歳男性で, DDDペースメーカー植え込み後に失神が再発, 排尿後の失神発作時に心電図モニター上ペーシング調律に伴いー過性のST上昇を認めた.冠動脈造影で軽度の硬化性病変と冠攣縮傾向を認め, ジルチアゼム投与を開始したが血圧低下のため, エフエドリンを併用した.以後, 内服は自己中断したが, 11カ月間失神発作は出現していない, 頸動脈洞症候群では迷走神経反射に伴いST上昇が誘発されることがあり, 冠攣縮による可能性が示唆された.

We report the case of a 38-year-old man who had idiopathic ventricular fibrillation (VF) which initiated by abnormally short-coupled ventricular premature beats. VF was successfully prevented by the combination of pilsicainide, propranolol, and verapamil. In particular, the effects of pilsicainide are assumed to exert an important effect in controlling this arrhythmia. Class Ic drugs may be effective for preventing VF initiated by short-coupled VPBs.

健常成人24名 (男23例, 女1例, 平均年齢31歳) を対象に, 加算平均心電図のSpectral turbulence法 (STA) による解析結果の再現性につき, 従来のTime domain法 (TDM) と比較した.加算平均心電図は同―電極位置にて15分間隔で2回の記録を行ない, さらに電極位置の微妙な変化が再現性に及ぼす影響をみるため1週間後にも同様の方法で2回, 計4回の記録を行なった.TDMのRoot mean square voltage, およびSTの4つの定量的パラメーターは記録ことに変動を示したが, 15分間後よりも1週間後で変動が大きく, 測定値の再現性は15分間隔のほうが良好な結果であった.しかし, 従来の診断基準を適用した場合, 各記録間で陰性と診断された結果の―致率は, TDMで96～100%, STAでも92～96%であり, TDMには若干劣るものの, STAによる診断感度およびその再現性は良好であった.

Circadian Variation of Vasovagal Syncope. Introduction. Circadian patterns have been demonstrated for several cardiovascular catastrophes. Chronobiologic factors play a role in the emergence of vasovagal syncope (VVS); however, diurnal variation of syncopal episodes in VVS has not been reported previously. Methods and Results. We assessed daily distribution of the time of syncopal episodes in VVS. Time of syncope could be determined in 80 episodes in 54 patients (32 men and 22 women; mean age 37 years, range 12 to 67). Patients who were prescribed beta blockers or vasodilators, and who had syncopes related to alcohol intake, were excluded from the study. Head-up tilt testing was performed in 53 patients. The distribution of the episodes of VVS in 3-hour intervals differed significantly from uniform occurrence (P < 0.0001). with a peak frequency between 6 A.M. and noon (67.5% of total episodes). In patients who had experienced the initial syncope in the morning, most (78%) of the next syncopal episodes also occurred in the morning. There was no significant correlation between the time of last syncopes and tilt testing results. Conclusion. We demonstrated a prominent circadian variation in the frequency of VVS, with a peak in the morning. Recognition of the daily distribution of VVS is useful for patient education and therapeutic strategy. (J Cardiovasc Eleciroptiysiol. Vol. 11. pp. 1078-1080, October 2000)

A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance. We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day. No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration. This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.

A 14-year-old boy was admitted for the evaluation of recurrent syncope. His ECG on admission revealed a sinus rhythm with an undetermined QRS axis, T wave inversion at leads V3, V4 and abnormal q at leads I, aVL, V5 and V6. However, no underlying disease could be detected by any morphological examination. Programmed ventricular stimulation also induced no ventricular tachycardia or fibrillation (VF). Only signal-averaged ECG showed ventricular late potential and the cause of syncope was not clarified. As his brother with a similar ECG had died suddenly, he was prophylactically treated with an ICD. However, 14 months later he died suddenly after playing a video game. The ICD recorded VF, which was not converted despite 6 cardioversion attempts by the ICD. Progression of myocardial damages and/or elevation of defibrillation threshold may have been the cause of unsuccessful cardioversion.

Isoproterenol is widely used as a provocative medium for vasovagal responses during tilt testing. Dose of isoproterenol infusion is generally titrated empirically by increase in resting heart rate before tilt up. To determine the optimal increase in resting heart rate with isoproterenol for tilt-induced vasovagal responses, we studied 97 consecutive patients with unexplained syncope. After the end of a negative baseline tilt (80 degrees for 30 min), the isoproterenol tilt was performed using one of two protocols: two-stage isoproterenol-tilt protocol, with doses of 0.01 and 0.02 microg/kg per min for 10 min each, or one-stage isoproterenol-tilt protocol, with a dose of 1 or 2 microg/min for 10 min. The resting heart rate increase was defined as a percentage increase in the resting heart rate after isoproterenol infusion, compared to the baseline heart rate before the tilt test. In 117 tilt procedures, 28 (93%) of the 30 positive responses occurred with a resting heart rate increase of > or = 21%. With the resting heart rate increase of 60 and 100%, 18 (60%) and 27 (90%) positive responses were observed, respectively. In conclusion, the minimum resting heart rate increase of > or = 21% was required to provoke a vasovagal response during subsequent isoproterenol-tilt (80 degrees for 10 min). Preferably, heart rate should be increased to 60-100% by isoproterenol titration before tilting.

Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and JT intervals on 12 lead surface ECG before administration of these drugs were all within normal range. After administration of the drugs, coved-type ST segment elevation in the right precordial leads was observed with mild QRS prolongation, but there were no apparent changes in JT intervals. No serious arrhythmias were observed during the follow up periods. Since ST segment elevation with mild QRS prolongation was observed with both pilsicainide and flecainide, strong sodium channel blocking effects in the depolarisation may have been the main factors responsible for the ECG changes. As the relation between ST segment elevation and the incidence of serious arrhythmias has not yet been sufficiently clarified, electrocardiographic changes should be closely monitored whenever class Ic drugs are given. Keywords: class Ic antiarrhythmic drugs; Brugada syndrome; ST segment elevation

The aim of this study was to clarify the acute performance of steroid-eluting screw-in leads in comparison with that of nonsteroid screw-in leads for atrial free wall pacing. In 114 cases (68 males, 46 females, average age 70 years) with atrial free wall pacing by screw-in leads, pacing thresholds and P-wave amplitudes were compared at the time of implantation and 1 week later between 68 cases of nonsteroid and 46 cases of steroid-eluting screw-in leads. No significant differences were seen between the 2 groups at implantation in either voltage or current thresholds measured at pulse widths of 0.1, 0.3, 0.6, 1.0, 2.0 ms, or P-wave amplitudes. Pulse width thresholds at outputs of 2.5 V and 5.0 V were significantly lower for steroid leads 1 week after implantation (2.5 V: 0.34±0.27 ms nonsteroid vs 0.12±0.08 ms steroid, p

We report a case of runaway pacemaker with a ventricular pacing rate of 190 beats/min. The runaway occurred when the accelerometer became stuck due to the magnet application during VVIR pacing. Runaways in modern pacemakers are particularly rare, but they do still occur. The best solution for this phenomenon is generator replacement.

We retrospectively studied the clinical efficacy and safety of oral flecainide in 38 patients with symptomatic arrhythmias. Patients received 100 to 200 mg daily of flecainide for a mean of 25 months (range 8 to 50 months). All patients had normal cardiac function. Paroxysmal atrial fibrillation (PAF) was observed in 29 patients (76%). Other forms of arrhythmia included paroxysmal atrial flutter, seen in 3 patients (8%); premature atrial contraction and ventricular premature contraction, each seen in 2 patients (5%); and supraventricular tachycardia and ventricular tachycardia, each seen in 1 patient (3%). A complete response was obtained in 15 (52%) of 29 patients with PAF and a partial response in 8 patients (27%). The remaining 6 patients (21%) showed no response. A complete response was also obtained in 7 of 9 patients with other forms of arrhythmia. There were no differences in cardiac function and ECG parameters before and after treatment. Flecainide was withdrawn in 4 patients due to the development of electrocardiographic abnormalities. Three of these patients showed an atrial proarrhythmic effect. Abnormal ST elevations in the precordial leads were observed in 1 patient who received 200 mg of flecainide daily. In conclusion, flecainide was effective treatment for supraventricular and ventricular arrhythmias, but attention must be paid to the drug's potential proarrhythmic adverse effects.

Dislodgment of an atrial screw-in pacing lead is quite rare. This report describes a rare case of an atrial screw-in lead dislodgment 10 years after implantation. Although it is an uncommon complication, very late dislodgment can occur postoperatively, and careful follow-up is necessary.

In conclusion, filtered QRS duration in time-domain analysis of SAEs was influenced by gender and body characteristics in healthy subjects; however, the parameters in spectral turbulence analysis were not.

祖母がCREST症候群,全身性エリテマトーデス(SLE),慢性甲状腺炎,シェーグレン症候群,母親がSLE,シェーグレン症候群,娘がSLEを発症した1家系を経験したので報告した,血縁者17名を加えた20名と健常人コントロール20名の臨床症状, HLA,血液検査所見を検討した結果は以下のごとくである. (1)発症者および臨床症状(レイノー症状)の認められた6名全員が共通haplotype HLA A11, B 39 (16), CW 7, DRW 8を保有していた. (2)性差による検討では発症者および臨床症状のみられた血縁者は全員女性であった.臨床症状のみられなかった血縁者のうち,自己抗体の認められた者は男性では7名中1名(14.2%),女性では7名中4名(57.1%)で女性に多い傾向がみられた. (3)臨床症状のみられなかった血縁者の検討ではCH50の低下は14名中6名(42.9%)にみられ,健常人コントロールの20名中1名(5%)に比し有意に多くみられた(p