Radiofrequency catheter ablation (RF-CA) has demonstrated a high success rate in eliminating idiopathic left ventricular tachycardia (ILVT), and the target site is determined by the score of pace mapping or the Purkinje potential (PP) preceding the onset of the ventricular activation, which is considered to indicate the exit site of the reentrant circuit. However, only a few reports have described the potential obtained from the slow conduction zone. RF-CA was successfully performed in 8 patients with ILVT. Careful mapping of the left ventricle during tachycardia was carried out to find the diastolic potential (DP). A DP was obtained in 4 patients (group 1), but not in 4 others (group 2). The local electrogram was recorded from the distal tip of the ablation catheter during the RF current application in order to investigate the pattern of termination of ILVT. A DP was recorded at the point where the catheter was slightly pulled back to a site proximal to the exit site of the reentrant circuit at the left interventricular basal septum. In group 1, conduction block between the DP and PP eliminated ILVT in 3 out of 4 cases, and 1 case showed conduction block between the DP and ventricular potential. In 2 out of 4 patients in group 2, the local electrogram showed conduction block between PP and the ventricular potential when VT terminated. The ablation site in group 1 was located relatively more basal than that in group 2 in anatomy. A DP was obtained in a half of the cases with ILVT and RF-CA at this site could eliminate ILVT. A DP was obtained at a site relatively basal to the exit of the reentrant circuit and it is considered that this is a useful marker in terms of the successful ablation of ILVT. (Jpn Circ J 1999; 63: 917 - 923)

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Reactive oxygen species are thought to mediate reperfusion injury after rapid revascularization for acute myocardial infarction (AMI) and 8-epi prostaglandin (PG) F_{2 α}, a free-radical catalyzed product of arachidonic acid, has been proposed as an indicator of oxidative stress in vivo during myocardial reperfusion. The time course of urinary 8-epi PGF_2α excretion after primary coronary angioplasty (PTCA) for AMI was investigated, as well as the effect of prior administration of vitamin C. Urine samples, 1 before and 5 after primary PTCA (0-30, 30-60, 60-90, 90-120 and 120-150 min), were collected in 11 patients with AMI undergoing primary PTCA (Group 1), 10 patients with AMI treated with water-soluble vitamin C at an initial dose of 2.0 g followed by a constant infusion at 20 mg/min prior to primary PTCA (Group 2), and 6 patients with stable effort angina undergoing elective PTCA (Group 3). 8-epi PGF_{2 α} was measured by enzyme immunoassay. There were no significant differences in urinary 8-epi PGF_{2 α} excretion at baseline among the 3 groups. In Group 1, urinary 8-epi PGF_2α excretion (ng/mmol creatinine) significantly increased from 60±8 at baseline to 122±16 at 60-90 min (p<0.001), and declined to the baseline level at 120-150 min after primary PTCA. In Group 2, it also increased from 72±12 to 123 ±15 at 60-90 min (p<0.01), and the percent increase did not differ from that in Group 1. In Group 3, it remained unchanged during the study period. The free radical production is rapidly and transiently enhanced after primary PTCA for AMI, and vitamin C fails to suppress it. (Jpn Circ J 1999; 63: 924 - 928)

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Complications of mitral valve prolapse (MVP), among which serious ventricular arrhythmia and sudden death are of major importance, affect many individuals due to the high incidence of MVP itself in the community despite the actual low incidence of these complications. The present study investigated the incidence and distribution of ventricular arrhythmias according to their severity and relationship with the QT interval and dispersion of repolarization in uncomplicated isolated MVP (IMVP) cases. Fifty-eight uncomplicated IMVP patients, 33 patients with accompanying tricuspid valve prolapse (TVP), to compare its relationship with ventricular arrhythmia, and 60 age- and sex-matched control subjects were enrolled in the study. Individuals with accompanying cardiac or systemic disease, or who were on drug therapy that could potentially affect QT characteristics, were excluded. The incidence of ventricular arrhythmia was 48% in the IMVP group and 64% in the TVP group; the difference was statistically insignificant. In addition, the differences of the QT and Q peak T values were insignificant, whereas QT dispersion (QTd) and Q peak T dispersion (QpeakTd) values were significantly higher in the patient group (60±14, 54±14 ms, respectively) compared with the control group (42±10, 38±10 ms, respectively, p<0.001). Complex ventricular arrhythmias (Lown Grade ≥III) in the IMVP group had a significant relationship with QTd and QpeakTd (p<0.001), but not with QT or QpeakT. As a result of the study, it is concluded that TVP accompanying MVP does not increase the incidence of ventricular arrhythmia, that ventricular arrhythmia is related to QT dispersion rather than QT interval in IMVP, that the QT dispersion is a fairly good marker for identifying the high-risk group for serious ventricular arrhythmia and sudden death, and that QpeakT dispersion measurement is an additional indicator that could be an alternative when QT is difficult to determine in conditions such as high heart rate or the presence of U wave. (Jpn Circ J 1999; 63: 929 - 933)

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Results of recent studies suggest that proinflammatory cytokines cause myocardial contractile dysfunction, and that the drugs used to treat heart failure modulate the production of cytokines. This study was designed to examine the effects of digoxin in a murine model of heart failure induced by viral myocarditis. Four-week-old inbred DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis virus (EMCV). Digoxin was given orally in doses of 0.1, 1 or 10 mg/kg daily from the day of virus inoculation. Interleukin (IL)-1 β, IL-6 and tumor necrosis factor (TNF)-α production in the heart were measured on day 5 after EMCV inoculation by enzyme-linked immunosorbent assay. The 14-day mortality tended to be increased in mice treated with 1 mg/kg, and was significantly increased in the group treated with 10 mg/kg per day. Myocardial necrosis and cellular infiltration on day 6 were significantly more severe in the high-dose digoxin group than in the control group. In the animals treated with 1 mg/kg digoxin, IL-1β was significantly higher than in the control group. Intracardiac TNF-α levels were increased in a dose-dependent manner. These results suggest that digoxin worsens viral myocarditis, and that its use in high doses should be avoided in patients suffering from heart failure due to viral myocarditis. (Jpn Circ J 1999; 63: 934 - 940)

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To detect the minute electric potential inside the QRS complex, a new frequency domain method was designed using short-time First Fourier Transforms (SFFT) and high-frequency sampling (oversampling). SFFT improved the frequency resolution by oversampling that was applied to this analysis. The electric potential data of 15,000 points received weighted, running average processing and was subtracted from the original waveform to reduce the low-frequency component. The data in a segment of 160 ms, including QRS, was processed by frequency analysis with the SFFT computation routine. The ECG of healthy individuals was analyzed by this method and its usefulness evaluated. The processing waves of the X-axis, Y-axis, and Z-axis of a representative normal subject were formed into 3 groups of peak electric potential. SFFT enabled the detection of the structure inside the QRS complex without signal averaging, and is considered capable of evaluating the process of excitement inside the QRS complex in the various heart diseases. (Jpn Circ J 1999; 63: 941 - 944)

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Although treadmill exercise involves a more familiar range of motions and is thus more physiological in terms of daily activity than cycle ergometer exercise, difficulties in controlling the exercise intensity have limited its utility. As heart rate (HR) has been used as a measure of exercise intensity, controlling HR should allow for the proper control of exercise intensity during treadmill exercise. Thus, a servo-controller framework was applied to regulate HR during treadmill exercise. After estimating an averaged transfer function from speed command to HR, feedback parameters were optimized via a computer simulation in order to achieve a quick and stable HR response. The performance of the servo-controller of HR was then examined in 10 healthy subjects. Standard deviations of the steady-state difference between the target and measured HRs were 2.7±0.9 and 5.0±1.4 beats/min in the stepwise and ramp target HR protocols, respectively. The rise time to reach 90% of the target HR was 93±20 s in the stepwise protocol. It was concluded that a treadmill implemented with a negative feedback mechanism made it possible to precisely regulate HR and thus exercise intensity. (Jpn Circ J 1999; 63: 945 - 950)

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Proinflammatory cytokines, ie, tumor necrosis factor-alpha (TNFα), participate in the development and the progression of congestive heart failure (CHF). On the other hand, an anti-inflammatory cytokine may neutralize the proinflammatory cytokines of CHF. Interleukin-10 (IL-10) is known to suppress the synthesis of proinflammatory cytokines. IL-10 and the IL-10 receptor system was investigated in comparison with the behavior of TNF α in 68 patients with various causes of CHF (mean age: 61 years) and in 31 normal subjects (61 years). The circulating IL-10 level was higher in CHF patients than in normal subjects (p<0.05). The TNFα level was higher in CHF patients than in control subjects (p<0.005). The ratio of IL-10 to TNFα tended to be higher in control subjects than in patients with CHF (p=0.09). With lipopolysaccharide treatment, the release of IL-10 was more enhanced from mononuclear leukocyte of patients with CHF than from control subjects (p<0.05). The expression of the IL-10 receptor estimated by flow cytometry of mononuclear leukocytes was higher in the CHF patients than in the normal subjects. The IL-10/IL-10 receptor system was activated, at least partly, to downregulate an excess of TNF α in patients with advanced CHF. IL-10 may be an important inherent component of the cytokine network of CHF. (Jpn Circ J 1999; 63: 951 - 956)

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It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO₂) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg po). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat^-1 m^-2, p<0.05) at a comparable MVO₂ per beat with a marginal increase in LV contractility index (E_es) (from 2.34 to 2.76 mmHg m^-1 m^-2, p=0.08), resulting in a decrease in mechanical efficiency (EW/MVO₂) (from 25.9 to 22.1%, p<0.05). In contrast, zatebradine did not decrease E_es (from 2.34 to 2.24 mmHg ml^-1 m^-2, NS), but increased EW (from 0.39 to 0.42 J beat^-1 m ^-2, p<0.05 vs basal level) without a change in MVO₂ per beat, resulting in improved mechanical efficiency (from 25.9 to 29.7%, p<0.05 vs basal level). These results suggest that mild bradycardia is energetically advantageous and does not decrease myocardial contractility and performance, whereas pacing-induced tachycardia worsens cardiac mechanics and energetics in patients with LV dysfunction. Thus, the oxygen-saving effect of bradycardia may be beneficial for the treatment of heart failure. (Jpn Circ J 1999; 63: 957 - 964)

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The exercise capacity of patients with chronic heart failure (CHF) is greater when assessed by the treadmill rather than the bicycle ergometer, but the mechanism of this difference has not been clarified. The present study aimed to determine the difference between the hemodynamics of these exercise modes and the mechanism underlying the different peak oxygen uptake (VO₂). Patients (n=18) underwent a bicycle test and treadmill test using individual ramp protocols. Respiratory gas analysis and hemodynamic measurements with an opti-catheter were performed during both exercise tests. The peak VO₂ was significantly larger in the treadmill test than the bicycle test (1410±292 vs 1630±331 ml/min, p<0.001). Both the peak cardiac output (Q; 10.2±2.2 vs 10.9±2.1 L/min, p<0.001) and the peak arteriovenous oxygen difference (a-v O₂ diff; 13.9±1.5 vs 15.0±1.2 vol%, p<0.001) were also significantly higher in the treadmill test. The relative contribution of Q and a-v O₂ diff to the increased peak VO₂ was equivalent, which suggests that both Q and a-v O₂ diff. Contribute equally to the different peak VO₂ responses in CHF. (Jpn Circ J 1999; 63: 965 - 970)

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This study describes the acute and chronic effects of dual-chamber (DDD) pacing in 14 consecutive patients with hypertrophic obstructive cardiomyopathy (HOCM), whose symptoms were refractory to drug therapy. Although left ventricular (LV) outflow tract pressure gradients diminished from 106±47 to 62±33 mmHg (p<0.001) by temporary pacing, the residual pressure gradients were >30 mmHg in the majority of those with concomitant reductions in cardiac output. The DDD pacing was judged as insufficient by the acute study in the majority of patients. A dual-chamber pacemaker was, however, implanted in 11 patients, and the chronic pacing effects were evaluated. All symptoms (syncope, fainting, palpitation and dyspnea) subsided within 1 month. Left ventricular outflow tract pressure gradients diminished from 99±56 to 21±13 mmHg (p<0.004) at 1 week after, and to 17±12 mmHg (p<0.002) at 1 year after the implantation, as measured by Doppler echocardiography. Echocardiogram showed disappearance of the systolic anterior motion of the mitral valve, and significant regression of the septal hypertrophy (from 18.5±4.3 to 15.7 ±4.1 mm, p<0.04). There was no significant correlation between the acute and chronic pacing effects in the reduction of the pressure gradients or symptomatic improvement. These results suggest that DDD pacemaker implantation is an effective treatment without any serious risks for patients with drug-refractory HOCM. The chronic-pacing effect in the reduction of the pressure gradient, the regression of hypertrophy and symptomatic improvement cannot be predicted by the assessment of temporary DDD pacing. (Jpn Circ J 1999; 63: 971 - 975)

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Although disturbances of the fibrinolytic system and serum lipid, and the presence of inflammation, may be risk factors for coronary artery disease (CAD), few reports have investigated these relationships in Japanese patients. Data on 106 patients (79 men and 27 women, mean age 62.3 years) with atherosclerotic lesions on the coronary angiogram were evaluated prospectively to identify whether the factors were useful in predicting the risk of coronary events during a follow-up of 50±4 months. Of the 106 patients who were followed, 11 patients had coronary events (4 acute myocardial infarction and 7 unstable angina pectoris). In univariate Cox analyses, a high level of tissue-plasminogen activator (t-PA), apolipoprotein CII, C-reactive protein (CRP), and a low level of high-density lipoprotein-cholesterol (HDL-C) was each associated with a significant increase in the risk of future cardiac events. The stepwise model of Cox proportional hazards analysis selected only a high level of t-PA and CRP as predictors of cardiac events. Controlling for any risk factor did not lower the relation between t-PA and the risk of cardiac events, whereas the relative risk of cardiac events in CRP was not significant when controlled for HDL-C. Thus, in prospective data obtained from a cohort of Japanese patients with coronary atherosclerotic lesions, the elevation of t-PA was an independent predictor of subsequent cardiac events. The prognostic role of CRP in cardiac events was related to a low level of HDL-C. (Jpn Circ J 1999; 63: 976 - 980)

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This study was conducted to investigate therapeutic methods for end-stage renal disease (ESRD) by retrospectively analyzing in-hospital outcome and long-term outcome in patients who underwent either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Ninety-two patients underwent PTCA and 47 underwent CABG, and the initial success rates were 87% and 85%, respectively. As major in-hospital complications, in the PTCA group 1 died (1%), 2 required emergency CABG (2%), and 2 had Q-wave myocardial infarction (2%); in the CABG group, 7 died (15%) and 3 had Q-wave myocardial infarction (6%). As for the long-term outcome, although there were no differences in the incidence of death or the incidence of cardiac death between the 2 groups, the cumulative proportion of patients free of death, myocardial infarction, CABG and repeat PTCA was lower in the PTCA group, which was mainly due to a higher incidence of repeat PTCA in that group. The incidence of cardiac death was low for both groups among the patients attaining complete revascularization. Twenty-three percent of the patients required cross-over implementation of PTCA and CABG. In conclusion, it is necessary to aim for complete revascularization using both treatments for a better prognosis in patients with ESRD. (Jpn Circ J 1999; 63: 981 - 987)

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Aortic damage during the prediabetic stage of diabetes mellitus (DM) was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II DM. In 30 OLETF and 30 nonDM rats, an oral glucose tolerance test was performed at 10, 20 and 30 weeks of age. At 15 and 30 weeks, intravascular ultrasound images and aortic pressure were recorded and the stiffness parameter β was calculated. The aortic walls were excised at 5, 15 and 30 weeks for histopathology and the measurement of hydroxyproline. At 10 weeks, blood glucose (mg/dl) and insulin concentrations (ng/ml) of the OLETF rats (2 h; 168±30 and 0.82 ±0.15) were significantly high (nonDM: 118±15; p=0.02 and 0.16±0.64; p=0.003). At the prediabetic stage (15 weeks),β in the OLETF rats (2.5±0.9) was larger than in nonDM rats (1.4±0.4; p=0.0006), and the collagen (hydroxyproline) content/dry weight (mg/g) of the aortic wall was significantly higher in OLETF (33.5±3.1) than in nonDM rats (28.7±3.5; p<.05). Histopathological examination showed that from 15 weeks of age the medial wall thickness increased gradually. In the prediabetic stage, collagen accumulation may contribute to impairment of aortic wall stiffness in the OLETF rats, which would accelerate the aging process in the aortic wall. (Jpn Circ J 1999; 63: 988 - 993)

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Transcatheter coil embolization of the patent ductus arteriosus (PDA) has been frequently used in children, especially for small lesions. It was attempted in 3 adults using Cook detachable coils. For 2 of the patients, relatively old age and heart failure were the reasons for choosing coil embolization of the PDA. In the remaining patient, who had Wolff-Parkinson-White syndrome, coil embolization was performed after radiofrequency catheter ablation of Kent's bundle. Their respective minimal PDA diameters were 5.0 mm, 4.5 mm and 4.0 mm measured by transesophageal echocardiography. Two coils were placed in 2 patients and 1 coil in the remaining patient. After the procedures, the size of the left ventricle decreased and heart failure was improved in 2 patients, although all 3 patients had a residual shunt, which caused hemolytic anemia in 2 patients. Repeat coil-embolization procedures resulted in complete occlusion and the hemolysis disappeared in these patients. In adult patients who have heart failure due to large PDA, coil embolization with detachable coils, even if residual shunt persists, is useful for improvement of the heart failure. In cases of hemolysis related to residual shunt, a second coil-embolization procedure can improve it completely. (Jpn Circ J 1999; 63: 994 - 998)

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This report presents an adult patient with conversion of typical to atypical atrioventricular nodal reentrant tachycardia (AVNRT) after slow pathway ablation. Application of radiofrequency energy (3 times) in the posteroseptal region changed the pattern of the atrioventricular (AV) node conduction curve from discontinuous to continuous, but did not change the continuous retrograde conduction curve. After ablation of the slow pathway, atrial extrastimulation induced atypical AVNRT. During tachycardia, the earliest atrial activation site changed from the His bundle region to the coronary sinus ostium. One additional radiofrequency current applied 5 mm upward from the initial ablation site made atypical AVNRT noninducible. These findings suggest that the mechanism of atypical AVNRT after slow pathway ablation is antegrade fast pathway conduction along with retrograde conduction through another slow pathway connected with the ablated antegrade slow pathway at a distal site. The loss of concealed conduction over the antegrade slow pathway may play an important role in the initiation of atypical AVNRT after slow pathway ablation. (Jpn Circ J 1999; 63: 999 - 1001)

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A 85-year-old woman with diabetes mellitus and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The T wave during right ventricular pacing was tall and tent-shaped while the concentration of serum potassium was high, and its amplitude during pacing was decreased after correction of the serum potassium level. Simultaneously with the correction, normal sinus rhythm was restored. The cause of hyperkalemia was considered to be several doses of loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), prescribed for her lumbago by an orthopedic specialist, in addition to the long-term intake of imidapril, an angiotensin-converting enzyme inhibitor (ACEI), prescribed for her hypertension by a cardiologist. This case warns physicians that the combination of NSAID and ACEI can produce serious side effects in aged patients who frequently suffer from hypertension, diabetes mellitus, ischemic heart disease, and degenerative joint disease. (Jpn Circ J 1999; 63: 1002 - 1003)

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A 65-year-old woman with aortic stenosis, ischemic heart disease, and Graves' disease had complained of effort angina. She then suffered from liver dysfunction due to treatment with antithyroid drugs. One year after the start of radioiodine administration, she demonstrated unstable angina with palpitation and sweating. Laboratory studies revealed a recurrent hyperthyroid state, and a second coronary angiogram revealed progressive ischemic heart disease. Combined coronary artery bypass grafting, aortic valve replacement, and total thyroidectomy were performed. The postoperative course was uneventful without any problems associated with hyperthyroidism or hypothyroidism. Combined cardiac surgery and total thyroidectomy can be performed safely if the perioperative levels of thyroid hormone are maintained at euthyroid or hypothyroid levels. (Jpn Circ J 1999; 63: 1004 - 1006)

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An implantable cardioverter defibrillator (ICD) was implanted in 2 patients with ventricular tachyarrhythmia related to old myocardial infarction, and defibrillation tests were attempted at the time of ICD implantation and at 2 or 4 weeks after the operation. Ventricular fibrillation (VF) was induced by T-wave shocks, but the amplitude of the ventricular electrogram was different in each VF. In most of the VFs with large ventricular electrograms, the local activity was appropriately detected. However, many undersensed beats were observed in other VFs that had fine ventricular electrograms and a longer time was needed before delivering the shock. The amplitude of the ventricular electrogram might be small in some cases of VF and this might result in undersensing and/or unsuccessful defibrillation. Close attention must be paid to the amplitude of ventricular activation in each VF to avoid possible difficulty in ICD therapy. (Jpn Circ J 1999; 63: 1007 - 1010)

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