Lowering serum total cholesterol is shown todecrease the risk of coronary heart disease (CHD) in Western countries,but evidence is limited regarding cerebral infarction (CI). Thepresent study used the Kyushu Lipid Intervention Study to examinethe risks of CHD events and CI in relation to reduction in serumtotal cholesterol. Subjects were 4,615 men aged 45-74 years withserum total cholesterol of 220 mg/dl (5.68 mmol/L) or greater whohad no history of CHD events or stroke. CHD events and CI numbered125 and 92, respectively, in a 5-year follow-up. After adjustmentfor potential confounding factors, the relative risks of CHD eventsand CI for 15% or greater reduction in total cholesterol, comparedwith less than 5% reduction, were 0.78 (95% confidence limit [CL]0.46-1.32) and 0.39 (95% CL 0.22-0.69), respectively. As comparedwith on-treatment cholesterol levels of 240 mg/dl (6.20 mmol/L)or higher, the risk of CHD events was approximately 50% lower across 3categories below 240 mg/dl (6.20 mmol/L), and that of CI was 70%lower at 2 categories below 220 mg/dl (5.68 mmol/L). Lowering serumtotal cholesterol below 220 mg/dl (5.68 mmol/L) seems desirablewith regard to the prevention of CI. (Circ J 2003; 67: 473- 478)

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This study aimed to clarify whether body mass index (BMI), waist/hip ratio (WHR) or percent body fat (%fat) is associated with coronary artery disease (CAD) in Chinese type 2 diabetic patients in Taiwan. A total of 463 patients were recruited. BMI and WHR were measured by standard methods and %fat by bioelectrical impedance. CAD was diagnosed as acute myocardial infarction, angina pectoris, or an electrocardiogram showing `coronary probable or possible' according to the Minnesota codes. Age, sex, diabetes duration, hypertension, smoking, fasting plasma glucose, hemoglobin A_1c,and serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were treated as confounders. Results showed that 144 patients had CAD. Age, hypertension, HDL-C and %fat were independently associated with CAD. CAD prevalence was 25.5%, 26.8%, 31.9% and 43.0%, respectively, for the first to fourth quartile of %fat (p<0.05). Multivariate-adjusted odds ratio for CAD for every 1% increase in %fat was 1.02 (1.01-1.03); and 1.01 (0.73-1.88), 1.26 (0.69-2.32) and 2.11 (1.09-4.07) for the second to fourth quartile, respectively, compared with the first quartile. BMI and WHR were not associated with CAD in similar analyses. In conclusion, %fat was a better predictor for CAD than BMI and WHR in Chinese type 2 diabetic patients in Taiwan. (Circ J 2003; 67: 479 - 484)

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The present study investigated both the clinical significance of atrial fibrillation (AF) before right atrial appendage (RAA) pacing and the influence of prolonged P wave on AF occurrence in RAA-paced patients with sick sinus syndrome (SSS). Fifty-seven patients (age 68±10 years; 19 men, 38 women) with SSS who underwent RAA pacing were divided into 2 groups: 23 patients without AF before pacing (I + II; Rubenstein I or II) and 34 patients with AF before pacing (III; Rubenstein III). The P wave duration in intrinsic rhythm and with RAA pacing were measured on the standard electrocardiography in leads II and V₁ with the use of a digitizing tablet. Group III was further subdivided into 2 groups: 20 patients (IIIb) with a paced P wave >130 ms in both leads II and V₁ and the other 14 patients (IIIa). The duration of the intrinsic P wave in leads II and V₁ was significantly greater in group III than in group I + II (119±20 vs 108±21 ms, p=0.0417, 106±16 vs 95±21 ms, p=0.0258, respectively). During the follow-up of 40±21 months, AF recurrence was significantly higher in group IIIb than in groups IIIa and I + II (17/20 vs 5/14 vs 2/23 p<0.0001). A few occurrences of AF were observed by conventional RAA pacing in patients without AF before pacing. However, SSS with AF before pacing caused a significant intra-atrial conduction disturbance and a high incidence of AF recurrence after implantation of RAA pacing, especially in patients with a prolonged paced P wave, in whom new pacing modalities may be needed to shorten paced P wave duration and prevent AF. (Circ J 2003; 67: 485 - 489)

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It has been reported that some patients with acute myocarditis have transient ventricular thickening associated with narrowing of the left ventricular cavity caused by interstitial edema. The present study investigated this phenomenon in 20 patients with acute myocarditis. Based on the sum of the interventricular septal wall thickness and left ventricular posterior wall thickness (IVST + PWT), measured by M-mode echocardiography, patients were divided into group A (IVST + PWT ≥25 mm, n=12) and group B (IVST + PWT <25 mm, n=8). The IVST + PWT was 31.8 ±3.5 mm in group A and 21.9±2.7 mm in group B (p<0.0001). The left ventricular end-diastolic dimension (LVDd) was 42.3±6.0 mm in group A and 49.4±6.7 mm in group B (p<0.05). The stroke volume (SV) was 41.1±20.5 ml and 73.0±32.3 ml in groups A and B, respectively (p<0.05). The left ventricular ejection fraction (LVEF) was similar in group A (47.9±13.0%) and group B (56.9±9.0%). The SV correlated inversely with IVST + PWT (r=-0.62, p<0.01), and directly with both the LVDd (r=0.95, p<0.0001) and LVEF (r=0.64, p<0.01). The LVDd correlated inversely with IVST + PWT (r=-0.62, p<0.01). In conclusion, the reduction in SV that occurs during the acute phase of myocarditis is not only the result of systolic dysfunction, but also of the concentric left ventricular wall thickening associated with myocardial interstitial edema, which results in narrowing of the left ventricular cavity at end diastole. (Circ J 2003; 67: 490 - 494)

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Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac potassium or sodium channel genes, with 6 different genotypes thus far identified. However, it is unknown whether these genotypes can be differentiated by QT variables. The electrocardiograms obtained from 16 patients with a mutation in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc) and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected interval from T peak to T end (Tpec) was measured in lead V₅. The maximum QTc, QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2 patients than in the controls. However, there were no significant differences in these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion was significantly increased in the LQT2 patients (78±25 ms) compared with the LQT1 patients (29±15 ms) and controls (26±19 ms). These results suggest that increased lag of the peak of the T wave in each precordial lead (QTpc dispersion) may be a possible index to differentiate LQTS patients with HERG mutation from those with KCNQ1 mutation. (Circ J 2003; 67: 495 - 498)

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The development of quantitative gated single-photon emission computed tomography (SPECT) has enabled the assessment of left ventricular perfusion, function and wall thickness in a single examination. Accordingly, the present study used gated SPECT to assess the benefit of coronary artery bypass grafting (CABG) in patients with coronary artery disease; 47 of those patients were evaluated before and 5 months after CABG. As a result of coronary revascularization, a significant improvement was observed in global ejection fraction (50±12 → 53±11%; p<0.05). In 107 revascularized territories, the average regional reversible defect score (0.8±0.5 → 0.2 ±0.3; p<0.0001), average regional perfusion score at rest (0.6±0.6 → 0.3±0.4; p<0.0001), average regional wall motion score (0.9±0.7 → 0.7±0.5; p<0.05), and end-diastolic wall thickness (8.1±1.3 → 8.6±1.5 mm; p<0.0005) all improved significantly. Even in 34 non-revascularized territories, the average regional reversible defect score (0.5±0.7 → 0.2±0.5; p<0.03), average regional wall motion score (0.8±1.1 → 0.5 ±1.0; p<0.03) and end-diastolic wall thickness (8.0±1.4 → 9.1±2.0 mm; p<0.03) all improved significantly. These results indicate that improvement in myocardial ischemia, hibernation and left ventricular function with CABG can be assessed in detail with gated SPECT. (Circ J 2003; 67: 499 - 504)

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The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure (CHF) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities. Twenty-eight patients with CHF were randomized to the exercise or control group. The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated. After 3 months, walking performance increased only in the exercise group (488±16 to 501±14 m [control]; 497±23 to 567±39 m [exercise, p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change in either group (4.2±0.5 to 4.5±0.4% [control]; 4.3±0.5 to 4.6±0.4% [exercise]), but that in the posterior tibial arteries increased only in the exercise group (4.1±0.5 to 4.1±0.3% [control]; 3.6±0.3 to 6.4±0.6% [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs, but not in the untrained upper limbs. Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities. (Circ J 2003; 67: 505 - 510)

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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. (Circ J 2003; 67: 511 - 514)

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In patients with implanted DDD pacemaker, cardiac output is maximal when atrioventricular (AV) delay is set to give the maximum QT interval (QTI). QTI is used as a sensor of a rate-responsive pacemaker and the evoked QTI (eQTI) is measured as the time duration from the ventricular pace-pulse and the T sense point, which is the steepest point of the intracardiac T wave. The relationship between the changes in eQTI according to AV delay variations and cardiac function was studied in 13 patients (74.2±9.3 [SD] years old) with an implanted QT-driven DDDR-pacemaker. A special software module was downloaded into the pacemaker memory and a personal computer equipped with the special software was connected to the programmer for eQTI date-logging. AV delay was set at 100, 120, 150, 180 and 210 ms. Delta eQTI was defined as maximal eQTI - minimal eQTI. The ejection fraction (EF) was measured by echocardiography. When the AV delay was prolonged, eQTI gradually increased and reached a peak, and then decreased. Delta eQTI in patients with reduced cardiac function (EF <40%) was significantly greater than that in normal cardiac function (EF >55%, 7.6±4.9 vs 2.7±9.8 ms, p<0.05). There was significant negative correlation between EF and delta eQTI (r=-0.63, p<0.05). The peak of changes in eQTI according to AV delay variations was steeper in patients with reduced cardiac function than in those with normal cardiac function. In conclusion, changes in eQTI according to AV delay variation are greater in patients with reduced cardiac function than in those with normal cardiac function, and the AV delay that gives the maximal eQTI can be easily determined in patients with reduced cardiac function. (Circ J 2003; 67: 515 - 518)

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The purpose of this study was to determine whether candesartan and its combination with probucol reduce restenosis after coronary stenting. A total of 132 patients who successfully underwent stenting were randomly assigned to a control group (n=45), a candesartan group (8 mg daily, n=43), or a candesartan plus probucol group (+ probucol 500 mg daily, n=44). No differences in late loss were observed between the control and candesartan groups. In the candesartan plus probucol group, late loss was significantly smaller than in the control and candesartan groups (p=0.003, 0.015). The restenosis rate was 27% in the control group, 26% in the candesartan group (p>0.99), and 11% in the candesartan plus probucol group (p=0.104 vs the control group and p=0.103 vs the candesartan group). Intravascular ultrasound revealed no differences in stent area among the 3 groups, and no differences in lumen area or in intimal hyperplasia area between the control and candesartan groups. However, the intimal hyperplasia area in the candesartan plus probucol group was significantly less than that in the control and candesartan groups (p<0.001, p<0.001). This study demonstrated that candesartan failed to inhibit the neointimal hyperplasia and although the combination treatment did reduce neointimal hyperplasia, it did not statistically reduce the restenosis rate. (Circ J 2003; 67: 519 -524)

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To assess the coronary flow velocity - pressure relationship distal to a stenosis, and to evaluate the influence of microvascular abnormalities on this relationship, coronary flow velocity and coronary pressure were measured simultaneously in 38 patients (42 vessels). The instantaneous peak coronary flow velocity was plotted against the simultaneous measured distal coronary pressure, and the slope of the relation in the phase of diastolic flow decrease was calculated as the flow - pressure slope index (FPSI) and the X-intercept of the slope was calculated as zero-flow pressure (Pzf). The slope of the curve increased from 2.0±2.6 to 4.5±4.1 (p<0.001) and the X-intercept decreased from 42±16 to 27±13 mmHg (p<0.001) after papaverine injection. After successful coronary intervention, Pzf increased from 23±10 to 35±11 (p<0.01) and FPSI decreased from 6.8±5.1 to 3.5±1.8 (p<0.05). Pzf was higher in patients with an old myocardial infarction. It is feasible to assess the relationship between coronary flow and pressure distal to a stenosis in the clinical setting, and the relationship may provide additional information regarding coronary microcirculation. Microvascular abnormalities may play an important role in the coronary flow - pressure relationship distal to stenosis. (Circ J 2003; 67: 525 - 529)

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A double-blind, randomized placebo-controlled study was conducted to evaluate the feasibility of the long-term use of low-sodium soy sauce and miso in the general Japanese population and its effect on blood pressure (BP). Forty men and 24 women were randomly allocated to a low-sodium group (n=32) or a control group (n=32). Low-sodium soy sauce and miso, which were approximately 25% and 20% lower in salt content than common soy sauce and miso, were used in the study. The change in BP after a 6-week intervention was evaluated. There were no significant differences in age, sex, body mass index, BP or hypertension between the 2 groups before intervention. After the 6-week intervention, no significant change in BP was observed in the entire cohort. However, in those aged 40 years and older, 6.4 mmHg net reduction in diastolic BP with no significant change in systolic BP was noted in the low-sodium group. Taste evaluation for the low-sodium seasoning was considerably good. Replacing soy sauce and miso of the common type with the low-sodium alternative is feasible in the general population and could be the basis for a salt reduction strategy in the Japanese diet. (Circ J 2003; 67: 530 - 534)

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Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI. (Circ J 2003; 67: 535 - 538)

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Forty octogenarians (OCTO) undergoing a variety of cardiac and thoracic aortic surgeries using cardiopulmonary bypass (CPB) between 1994 and 2002 were retrospectively studied. The results were compared with those of high-risk younger patients aged less than 60 years (YOUNG) (n=89). All patients had an expected operative mortality of EuroSCORE 5 and over. The EuroSCORE score was 9.9±3.3 (range, 5-18) in the OCTO group and 6.8±2.3 (range, 5-16) in the YOUNG patients (p<0.0001). There were 4 (10%) and 10 (11%) hospital deaths, respectively (p>0.99). Major postoperative complications occurred in 50% of the OCTO and 36% of the YOUNG patients (p=0.17). There were 10 and 7 late deaths, respectively. Actuarial survival including hospital death was significantly lower in the OCTO group than in the YOUNG (p=0.033). Actuarial survival was significantly higher in female octogenarians than in male (p=0.046). The overall 3-year survival rate was 88±8% and 64±11%, respectively. Multivariate analysis showed that predictors of late death were male gender (p=0.0005) and a high EuroSCORE (p=0.0010). Cardiac and thoracic aortic surgery using CPB can be performed in octogenarians with an acceptable hospital mortality rate and gratifying medium-term survival results. (Circ J 2003; 67: 539 - 544)

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Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS) contributes to the progression of myocardial damage in myocarditis. Some dihydropyridine calcium channel blockers reportedly inhibit NO production and proinflammatory cytokines and the present study sought to clarify if a low dose of benidipine, a novel dihydropyridine calcium channel blocker, would ameliorate experimental autoimmune myocarditis (EAM). Rats with or without myocarditis were administered oral benidipine at a dose of 3 mg · kg^-1 · day^-1 for 3 weeks. Low-dose benidipine did not decrease blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis. Myocardial interleukin-1β (IL-1β) expression and IL-1β-positive cells were significantly less in rats with EAM that were treated with low-dose benidipine compared with untreated rats. Also, myocardial iNOS expression and iNOS-positive cells were markedly reduced in in the treated rats compared with the untreated group. Furthermore, myocardial NO production and nitrotyrosine expression were suppressed by the treatment in rats with EAM. The cardioprotection of low-dose benidipine may be caused by suppression of inflammatory cytokines and inhibition of NO production. (Circ J 2003; 67: 545 - 550)

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A rare case of coronary-to-pulmonary artery fistulas associated with formation of a saccular aneurysm that ruptured into the pericardium occurred in a 69 year-old-female who had experienced an episode of unconsciousness 3 months earlier and who suffered a second episode. She was diagnosed as having a cardiac tamponade caused by rupture of a coronary artery aneurysm formed by a left coronary artery - pulmonary artery fistula. The hemorrhage stopped after pericardial drainage. She was referred for surgical treatment of the aneurysm and suture closure of the afferent coronary artery into the aneurysm, transpulmonary closure of the fistulas, and aneurysmorrhaphy. There was adhesion between the aneurysm and pericardium. Her postoperative course was uneventful and she has remained well for 4 months after the operation. (Circ J 2003; 67: 551 - 553)

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A 53-year-old Japanese woman underwent investigation of her heart murmur. A continuous abdominal bruit was heard. Blood gas analysis and chest X-ray showed congestive heart failure. Enhanced computed tomography of the pelvis showed a 10×4 cm hypervascular tumor in the retroperitoneal space. Cardiac catheterization disclosed a cardiac output of 13.2 L/min and a step-up of oxygen at the right common iliac vein. Abdominal aortic angiography showed an extremely vascular pelvic tumor and rapid filling of the inferior vena cava. This is a rare case of a highly vascular pelvic tumor causing high-output heart failure because of th massive arteriovenous shunting. (Circ J 2003; 67: 554 - 555)

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A 74-year-old woman with hypertension and bronchial asthma had chest discomfort at rest and 4 days later was admitted to her nearby hospital because of the sudden onset of right hemiparesis. The hemiparesis had almost disappeared within 24 h of onset, but because an electrocardiogram showed sinus tachycardia and diffuse symmetrical T-wave inversion, she was referred for cardiac examination. Coronary angiography did not reveal any significant coronary artery stenosis, but left ventriculography revealed severe hypokinesis of the left ventricular apical region, which contained a 4×4-mm solid thrombus moving freely with a wavy motion. Moreover, the activity of both protein C and protein S had decreased. The thrombus disappeared after 2 weeks of anticoagulant treatment with warfarin. Her clinical course suggested that the transient cerebral ischemic attack was caused by embolism of the left ventricular thrombus associated with `tako-tsubo-like left ventricular dysfunction'. (Circ J 2003; 67: 556 - 558)

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A 56-year-old male with hypertrophic obstructive cardiomyopathy complicated with medically refractory paroxysmal atrial fibrillation and congestive heart failure was treated with percutaneous transluminal septal myocardial ablation. The resting left ventricular outflow tract gradient decreased from 70 mmHg to 0 mmHg after the procedure, and clinical symptoms improved dramatically. However, the patient died suddenly 19 months later and autopsy revealed nontransmural myocardial fibrosis with an irregular border in the interventricular septum. (Circ J 2003; 67: 559 - 561)

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The early detection of disease is important to keep people healthy, but it is not easy for elderly residents living in rural areas at a distance from well-equipped medical institutes to be examined. Therefore, the present study evaluated the usefulness of real-time telescreening of echocardiography using satellite communications. The participants in this study were 57 residents of a rural community in Japan. The resolution of the real-time ultrasound images sent by communications satellite was almost identical to that of the original images taken in the hospital. Although some problems remain to be solved, telescreening of echocardiography will be a practical method for public health in the near future. (Circ J 2003; 67: 562 - 564)

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Wrong:The background cardiovascular medications were withheld for at least 1 year for β blockers and for at least 6 months for others, and they were maintained through the study period.
Right:The background cardiovascular medications were given for at least 1 year for β blockers and for at least 6 months for others, and they were maintained through the study period.

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