Background The KCNQ1 single nucleotide polymorphism (SNP), G643S, is known to be associated with secondary long QT syndrome (LQTS) and to cause a mild reduction in KCNQ1 current. However, the precise incidence and its association with QT intervals remain unknown in the greater cohort of the population in Japan. Methods and Results The genotype was screened at codon 643 of KCNQ1 in 992 residents of a farming community. Eighty-eight individuals (female/male =52/36, 8.9%) were found to have a heterozygous G643S SNP. Matching both gender and age, we randomly selected 243 control (G643G) cases and compared the electrocardiogram parameters in both groups; QT, QTf (QT corrected by Fridericia's formula) intervals, the peak and the end of the T wave (Tpe) interval, and the Tpe/QT ratio. The latter 2 reflect the transmural dispersion of ventricular repolarization (TDR). In G643S carriers, both Tpe and Tpe/QT were significantly longer than in non-carriers, without significant QT prolongation. Both genders showed a tendency for an increase in QTf with aging. In females, both Tpe and Tpe/QT showed a similar significant increase with age, which was not observed in males. Conclusions In elderly females, G643S might be an independent risk factor for secondary LQTS by causing a greater TDR. (Circ J 2006; 70: 645 - 650)

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Background Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. Methods and Results Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3±10.3 years old). One point each was given for patients with advanced age (≥75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. Conclusion Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended. (Circ J 2006; 70: 651 - 656)

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Background The present study was conducted to determine the antiarrhythmic efficacy and safety of oral pilsicainide, a class Ic antiarrhythmic drug, in patients with persistent atrial fibrillation (AF). Methods and Results One hundred and eight patients (mean age, 58.9 years) with AF lasting ≥48 h and ≤6 months were randomized to receive pilsicainide 50 mg t.i.d. (n=58) or placebo (n=50) for 2 weeks in a double-blinded fashion. All patients underwent appropriate anticoagulation therapy with warfarin for ≥3 weeks prior to the study enrolment or after verification of the absence of left atrial thrombi by transesophageal echocardiography. After 2 weeks of treatment, an electrocardiogram was recorded to determine whether sinus rhythm was restored. Sinus rhythm was restored in 22.4% of patients treated with pilsicainide and in 2% treated with placebo (p=0.002). Cardioversion was less likely to occur with oral pilsicainide when the AF duration exceeded 2 months or if the left atrial diameter exceeded 45 mm. There was no significant difference in the adverse cardiovascular event rate between the pilsicainide- and placebo-treated groups. One patient in the pilsicainide group developed an atrial flutter without any hemodynamic deterioration. Conclusion A 2-week oral administration of pilsicainide is well tolerated and moderately effective in converting persistent AF into sinus rhythm. (Circ J 2006; 70: 657 - 661)

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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. (Circ J 2006; 70: 662 - 666)

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Background There is little information on the selection of antiarrhythmic agents for long-term prevention of paroxysmal atrial fibrillation (PAF). In the present study the preventive effects of pilsicainide (Pil) and cibenzoline (Cib) were compared in patients with PAF that was defibrillated at <48 h or ≥48 h after onset. Methods and Results A total of 60 patients (45 men, 15 women, mean age 66±10 years) were divided into 2 groups: Group I consisted of 22 patients in whom atrial fibrillation (AF) lasted for <48 h before cardioversion and Group II consisted of 38 patients in whom AF lasted for ≥48 h. A randomized, crossover protocol of treatment with Pil (150 mg/day) and Cib (300 mg/day) was used. Mean follow-up was 35±18 months. In Group I, the mean duration of maintenance of sinus rhythm was 12.3±2.9 months in patients treated with Pil, compared with 12.9±2.5 months in those givem Cib (p=NS between 2 groups). Actuarial event-free rates at 1, 3, 6, 12 months were 82%, 68%, 59% and 41%, respectively, in patients treated with Pil, and 91%, 77%, 68% and 50%, respectively, in those givenh Cib (p=NS between 2 groups). In Group II, the mean duration of maintenance of sinus rhythm was 1.6±0.5 months in patients treated with Pil, compared with 5.9±1.7 months in those given Cib (p<0.01). Actuarial event-free rates at 1, 3, 6, 12 months were 45%, 18%, 8% and 3%, respectively, in patients treated with Pil, and 63%, 45%, 29% and 16%, respectively, in those given Cib (p<0.05, at 12 months). Conclusions Prolonged tachycardia (≥48 h) in patients with PAF seems to cause electrical remodeling. Cib, a multichannel blocker, is considered to be more effective in preventing the recurrence of PAF in the electrically remodeled atria than Pil, a pure sodium-channel blocker. (Circ J 2006; 70: 667 - 672)

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Background In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI and cardiac rupture in humans. Methods and Results Levels of interleukin-8 (IL-8), polymorphonuclear leukocyte (PMN) elastase, monocyte chemotactic protein-1 (MCP-1) and MMP activity were measured in the pericardial fluid obtained from 28 patients with angina pectoris (AP group) and 16 patients with AMI (AMI group) undergoing cardiac surgery. In the AMI group, 5 were complicated with ventricular septal perforation (VSP) and the remaining 11 were not (non-VSP). Levels of IL-8, PMN elastase, MMP-2 and MMP-9 activity were all higher in the AMI group than in the AP group. In the AMI group, all levels other than MMP-2 activity were further elevated in cases with VSP compared with those in the non-VSP group. There was no significant difference in MCP-1 among the groups Conclusions Markers of neutrophil activation in the infarcted cardiac tissue seem to be elevated in AMI. Highly elevated levels of MMP-9 activity, which may be derived from neutrophils, and PMN elastase may be related to the pathophysiology of VSP or cardiac rupture in AMI. (Circ J 2006; 70: 673 - 678)

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Background The lack of studies on the simultaneous contributions of hospital and physician to the length of stay (LOS) for acute myocardial infarction (AMI) has hampered the development of hospital- and physician-level strategies by clinicians and policymakers. This study used 3 years of population-based data to examine the relationships of physician and hospital characteristics with LOS for AMI patients in Taiwan. Methods and Results Multiple regression analysis was carried out to explore the relationships, using the 2001-2003 National Health Insurance Research Database of the National Health Research Institute, Taiwan. The study samples were identified by a principal diagnosis of AMI (ICD-9-CM code 410), with a total of 19,907 eligible admissions. The mean LOS was 9.1 days. The results revealed that compared with district hospitals, the LOS was significantly longer in both medical centers and regional hospitals (both p<0.001). The LOS among patients attended by cardiologists was 28.0% shorter than those attended by physicians specializing in surgery, family medicine, or emergency medicine. Conclusions The results of this study demonstrate that there are wide variations among the different types of physician and levels of hospital in the LOS for AMI patients, which highlights the importance of developing national treatment protocols for AMI in order to reduce variations in hospital and physician behaviors. (Circ J 2006; 70: 679 - 685)

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Background Although a low ankle - arm index (AAI) has been reported to be associated with increased risk of cardiovascular mortality in several populations, no data exist concerning the impact of AAI for outpatients with suspected coronary artery disease (CAD) in the clinical setting. Methods and Results The present study enrolled 840 outpatients (age range 35-87 years, mean age 63.9±10.2) with suspected CAD. All patients underwent AAI measurements and coronary angiography, and based on the AAI values, they were divided into group A (AAI <0.9; n=191; CAD positive, 181) and group B (AAI ≥0.9; n=649; CAD positive, 509). Metabolic syndrome (MS), obesity, and level of the inflammatory biomarker high sensitive C-reactive protein (hsCRP) were compared between the 2 groups. The sensitivity, specificity, positive and negative predictive values in predicting CAD with an AAI value <0.9 in all patients were 26.2%, 93.3%, 94.8% and 21.6%, respectively. The patients in group A was significantly older and there was a higher female-to-male ratio than in group B. The presence of hypertension and diabetes mellitus, current smoking status, and levels of low density lipoprotein (LDL)-cholesterol level, uric acid and hsCRP differed significantly between the 2 groups. Group A had a higher percentage of high LDL-cholesterol level, high waist-to-hip ratio and more positive cases of MS than group B. Multivariate logistical regression analysis showed that AAI was related to MS, high levels of hsCRP (>3 mg/L) and uric acid (>7 mg/dl) with odds ratios of 1.769, 3.907 and 2.580, respectively. Conclusions The AAI test is an effective tool in predicting CAD in outpatients in clinical practise. (Circ J 2006; 70: 686 - 690)

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Background Although multislice spiral computed tomography (MSCT) is a promising technique for non-invasive coronary angiography, its usefulness in patients with stent implantation remains unclear. The aim of the present study was to compare the usefulness of MSCT with that of invasive coronary angiography for evaluating coronary stent patency. Methods and Results Thirty-one patients were enrolled after coronary stent implantation. Sixteen-slice MSCT scans were performed (39.0±21.8 days) before follow-up coronary angiography. After assigning an image score based on luminal visibility (1= poor, 2= fair, 3= good), factors determing image quality were analyzed. Among 42 implanted stents, 33 (78%) were assigned an image score of 3, 2 (5%) a score of 2, and 7 (17%) a score of 1. Image scores among stents with diameters ≥3.5 mm were significantly (p<0.05) higher than among smaller stents (≤3.0 mm). Stent strut thickness did not affect image quality, but coronary calcification significantly (p<0.01) hampered the image quality. After excluding 7 stents with image scores of 1, the sensitivity, specificity, positive and negative predictive values of MSCT to identify patent stents were 83%, 90%, 63% and 96%, respectively. Conclusions MSCT can provide useful and valuable clinical information for assessing stent patency during the follow-up period when patients are treated with relatively large diameter coronary stents. (Circ J 2006; 70: 691 -697)

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Background The aim of the present study was to clarify the effect of preinfarction angina pectoris (PIA) on myocardial blush grade (MBG), a simple marker of myocardial tissue-level reperfusion, in acute myocardial infarction (AMI). Methods and Results One hundred forty-two patients with first anterior wall AMI who were admitted within 6 h after onset of symptoms were examined. PIA was defined as typical chest pain within 48 h before onset of symptoms. MBG was evaluated by coronary angiography after reperfusion. Patients with MBG 2 or 3 (n=103) had a higher frequency of PIA and a lower frequency of diabetes mellitus than those with MBG 0 or 1 (n=39) (57% vs 28%, p=0.004, and 23% vs 44%, p=0.03, respectively). The former had a lower peak creatine kinase level and a greater left ventricular ejection fraction at predischarge than the latter (3,652±2,440 vs 5,507±3,058 IU/L, p=0.0002, and 57±12% vs 45±11%, p<0.0001, respectively). Multivariate logistic regression analysis showed that PIA (p=0.004) and diabetes mellitus (p=0.03) were independently associated with MBG 2 or 3 after reperfusion. Conclusions PIA has beneficial effects on myocardial tissue-level reperfusion evaluated by MBG in first anterior wall AMI. (Circ J 2006; 70: 698 - 702)

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Background Although cardiac resynchronization using biventricular pacing (BVP) results in significant clinical improvement in patients with chronic heart failure (CHF), there is no evidence of improvement in sympathetic nerve activity (SNA). Methods and Results Eighteen patients with CHF (dilated cardiomyopathy/ischemic cardiomyopathy =14/4) and left ventricular (LV) ejection fraction <40%, QRS duration >160 ms and dyssynchronous LV wall motion were classified into 2 groups based on the findings of ^99mTc-methoxyisobutyl isonitrile (MIBI) quantitative gated single-photon emission computed tomography (SPECT) (QGS). Resynchronization was considered to be present when the difference between the QGS frame number for end-systole for the LV septal and lateral walls (dyssynchrony index) disappeared. Group A achieved resynchronization after BVP, but not Group B. In group A, New York Heart Association functional class (p=0.0002), specific activity scale (p=0.0001), total defect score (p<0.05), and the heart/mediastinum ratio of delayed ¹²³I-metaiodobenzylguanidine imaging (p<0.05) were significantly improved after resynchronization. However, there was no significant change in group B. Conclusions Cardiac resynchronization after BVP can improve cardiac symptoms, exercise capacity, and SNA in patients with moderate to severe CHF. (Circ J 2006; 70: 703 - 709)

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Background The nucleus of the myocytes in human hypertrophic hearts is characterized by its bizarre shape and widespread clumping of chromatin. The functional significance has not been determined. Methods and Results Left ventricular (LV) endomyocardial biopsies obtained from patients with dilated cardiomyopathy (DCM, n=23), postmyocarditis (n=13), hypertrophic cardiomyopathy (HCM, n=21), apical hypertrophic cardiomyopathy (APH, n=11) and hypertensive heart disease (HHD, n=11), and from nonhypertrophic hearts (controls, n=14) were examined. Myocyte size and LV mass index were similar among the hypertrophic hearts, but the nuclear hypertrophy score (grade 0-3) was highest in hearts with systolic failure (DCM and postmyocarditis) and higher in those without it (HCM, APH, and HHD), compared with controls. So were biosynthetic activities such as DNA repair/synthesis, immunohistochemically assessed by proliferating cell nuclear antigen, transcription activity by spliceosome component of 35 kDa, and translation efficiency by 70 kDa S6 protein kinase. There were significant correlations between nuclear hypertrophy and each biosynthetic activity. Additionally, most of the proliferating cell nuclear antigen-positive nuclei co-expressed oxidative DNA damage markers. Conclusion A link is suggested between structural alteration and molecular biological events in the nuclei of myocytes from human hypertrophic hearts; the nuclear hypertrophy reflects increased biosynthetic activities of DNA repair/synthesis, transcription, and translation efficiency. (Circ J 2006; 70: 710 - 718)

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Background Ventricular fibrillation (VF) and sudden death (SD) may occur in patients with ST-segment elevation in the right precordial leads. The mechanism of such events is unclear, so the aim of the present study was to assess whether there is an underlying morphological or pathological abnormality in these patients. Methods and Results Fourteen consecutive patients (44±10 years old, all male) with ST-segment elevation of more than 2 mm in the right precordial leads underwent a cardiac evaluation, including right ventriculography and endomyocardial biopsy. The ST-segment changes after the administration of sodium-channel blockers were also evaluated. Two patients survived documented VF, 11 patients had chest pain or tightness, and another patient had a history of syncope. Only 1 patient had a family history of premature SD. The coronary angiograms were normal in all the patients. VF was induced in 5 patients (36%). Wall motion abnormalities of the right ventricle were detected in 4 patients (29%) and endomyocardial biopsy revealed features of cardiomyopathy in 7 patients (50%). In total, 9 (64%) of 14 patients exhibited wall motion abnormalities and/or pathologic findings. Conclusions Underlying cardiomyopathy was present in more than half of the present patients with ST-segment elevation in the right precordial leads. (Circ J 2006; 70: 719 - 725)

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Background The purpose of this study was to determine the initial and midterm results for repair of thoracic and abdominal aortic diseases using handmade stent-grafts (SGs). Methods and Results Between 1999 and 2004, 41 consecutive patients (31 patients with thoracic and 10 patients with abdominal aortic disease) underwent endovascular stent-graft repair using handmade SGs. The follow-up averaged 24.8±17.6 months. The technical and initial clinical success rates were 82.9% (34/41) and 80.5% (33/41), respectively. Primary type I or III endoleaks occurred in 12.2% (5/41) of the patients. The hospital mortality rate was 4.9% (2/41). Persistent type I or III endoleaks occurred in 9.8% (4/41) and SG migrations occurred in 4.9% (2/41) of the patients. Open surgical conversion was undertaken in 12.2% (5/41) of the patients because of an endoleak and/or migration. The mean change observed in the aneurysm diameter was -6.2±10.5 mm, and shrinkage in the diameter occurred in 51.4% (18/35) of the cases. There was 1 patient death because of aneurysm rupture. Neither stent fracture nor graft hole was observed. The overall clinical success rate during follow-up was 78.0% (32/41). Conclusion The initial and midterm results obtained after repair of the aortic diseases using handmade SGs were considered to be satisfactory. More surgical experience and long-term patient follow-up are both required to further reassess the effect of this treatment. (Circ J 2006; 70: 726 - 732)

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Background It is reported that there is a significant relationship between the calcification of the aortic arch detected by chest X-ray examination and stroke. However, the relationship between stroke and aortic calcification (AoC) detected during a mass screening using a mobile helical computed tomography (CT) unit remains unknown. Methods and Results The study population consisted of 2,618 subjects (1,345 men, and 1,273 women; mean age, 52.9±13.8 years) who participated in a mass CT screening for lung cancer and tuberculosis. In the present study, 28 subjects (18 men, and 10 women; mean age, 65.9±13.5 years) had a past history of cerebral infarction. There were no subjects with a past history of intracerebral or subarachnoid hemorrhage. The frequency of AoC was significantly higher in the infarction group who were older than 50 years of age. In logistic regression analysis, the AoC was a stronger contributor of infarction than sex, age, and risk factors. Furthermore, the odds ratio of AoC for subjects with a past history of infarction increased as the number of calcified segments increased, and these values were 1.82 (95% confidence interval (CI) 1.06-3.15) in men, and 2.53 (95% CI 1.12-5.75) in women. Conclusions These results suggest that detection of AoC during mass chest screening using a mobile helical CT unit is an effective way to evaluate the risk of cerebral infarction. (Circ J 2006; 70: 733 - 736)

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Background Obstructive sleep apnea (OSA) syndrome has a critical association with cardiovascular mortality and morbidity. Aortic elastic parameters are important markers for left ventricular (LV) function and are deteriorated in cardiovascular disease. Methods and Results Aortic elastic parameters and LV functions and mass were investigated in 40 patients with OSA (apnea - hypopnea index (AHI) ≥5) (mean age 51.3 ±9 years, 32 males) and 24 controls (AHI <5) (mean age 51.9±5.2 years, 19 males). All subjects underwent polysomnographic examination and recordings were obtained during sleep. They also underwent a complete echocardiographic examination and systolic and diastolic aortic measurements were noted from M-mode traces of the aortic root. There were no significant differences in the demographic data of the patients with OSA and the controls. Subjects with OSA demonstrated higher values of aortic stiffness (7.1±1.88 vs 6.42±1.56, p=0.0001), but lower distensibility (9.47±1.33 vs 11.8±3.36, p=0.0001) than the controls. LV ejection fraction was significantly lower in patients with OSA when compared with the control group (61.3±5.2% vs 65.9±8.4%, p=0.0001). LV diastolic parameters were also compared and were worse in the subjects with OSA than in the control subjects (mitral E/A: 0.91 ±0.42 vs 1.35±0.66, p=0.001; Em/Am: 0.86±0.54 vs 1.23±0.59, p=0.021). Respiratory disturbance index had a positive correlation with aortic stiffness (r=0.63, p=0.0001 and negative correlation with distensibility (r=-0.41, p=0.001). Conclusion Aortic elastic parameters are deteriorated in OSA, which has an extremely high association with cardiovascular disease. Increased aortic stiffness might be responsible for the LV systolic and diastolic deterioration in OSA syndrome. (Circ J 2006; 70: 737 - 743)

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Background The specific incidence of thrombotic pulmonary embolism (PE), tumor PE and tumor invasion into large veins according to tumor type and tumor site remains unclear. Methods and Results A total of 65,181 cancer patients were identified from 98,736 postmortem examinations. Thrombotic PE occurred in 2.32% of all cancer patients and comprised 88.6% of the total number of all PE events. The incidence of thrombotic PE was high in those with adenocarcinoma, leukemia and large cell carcinoma, and was low in those with hepatic cell carcinoma. The incidence of PE was high when tumor was present in hematogenous tissue, lungs, ovaries, pancreas and the biliary system, and was low when tumor was present in the liver. The incidence of tumor PE was high with large cell carcinoma, hepatic cell carcinoma and adenocarcinoma, and was also high when tumor was present in the lungs, ovaries, kidneys and liver. There was a significant correlation between the incidence of tumor PE and the incidence of tumor invasion into large veins. Conclusion The incidence of thrombotic PE, tumor PE and tumor invasion into large veins varies significantly according to tumor histopathology and tumor site. (Circ J 2006; 70: 744 - 749)

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Background The significance of inverted T waves remains unclear in patients with acute pulmonary embolism (PE). Methods and Results The relationship of the number of leads with inverted T waves to the severity of PE in 40 patients with acute PE was studied. Patients were classified into 3 groups according to the number of leads with inverted T waves on the admission electrocardiogram (ECG): 15 patients, ≤3 leads (group L); 12 patients, 4-6 leads (group M); and 13 patients, ≥7 leads (group H). In groups L, M and H, the rates of right ventricular dysfunction on echocardiography were 47%, 92% and 100% (p<0.01), respectively, and the rates of in-hospital complicated events (including death or the need for catecholamine support, cardiopulmonary resuscitation or mechanical cardiovascular support because of hemodynamic instability) were 0%, 8% and 46% (p=0.004), respectively. On multivariate analysis, arterial hypotension at presentation (odds ratio (OR) 8.96, p=0.049) and inverted T waves in ≥7 leads on the admission ECG (OR 16.8, p=0.037) were the only independent predictors of in-hospital complicated events. Conclusions The number of leads with inverted T waves may be a useful and simple marker of increased risk for early complications in patients with acute PE. (Circ J 2006; 70: 750 - 755)

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Background Cognitive function is impaired in elderly subjects, so the aim of the present study was to determine the role of arterial stiffness on cognitive function. Methods and Results Cognitive function and arterial stiffness were assessed by the Mini-Mental State Examination (MMSE) and measurement of the brachial - ankle pulse wave velocity (PWV), respectively. The cross-sectional association of the MMSE score and PWV was studied in 203 subjects (87 men, 116 women), all of whom were 85 years old. Sex distribution, systolic and diastolic blood pressures did not differ between the normal (MMSE score ≥24, n=128) and impaired MMSE groups (MMSE score <24, n=75). In contrast, the PWV was significantly increased in the impaired MMSE group than in the normal MMSE group (25.0±0.8 vs 22.9±0.5 m/s, p<0.05). In multiple regression analysis, the PWV was also independently and significantly associated with the MMSE score. Conclusions These results suggest that cognitive function could be predicted by arterial stiffness, as assessed by the PWV, in the very old. Preventing atherosclerosis may play an important role in preserving normal cognitive function until very old age. (Circ J 2006; 70: 756 - 761)

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Background The prognostic value of myocardial perfusion imaging (MPI) was investigated in patients with mildly impaired left ventricular (LV) function who had no chest pain but were suspected to have coronary artery disease (CAD). Methods and Results Consecutive patients (n=72, mean age =67) who had no chest pain but with mildly impaired systolic LV function (mean LV ejection fraction =52%) or LV asynergy and suspected to have CAD were followed up for 4.9 years after stress MPI. The follow-up time was censored at the occurrence of cardiac death, hospitalization for congestive heart failure (CHF), acute coronary syndromes (ACS), or revascularization. Images were scored using a 20-segment model and a 0-4 scale, and then the summed stress, rest, and difference scores (SDS) were calculated. During follow-up, there were 2 cases of cardiac death, 8 of hospitalization for CHF, 4 of ACS and 2 of revascularization. Cox regression demonstrated that SDS ≥4 was an excellent predictor of cardiac events in all patients (hazard ratio =4.2, p=0.01), and especially in diabetic patients (hazard ratio =28.4, p=0.01). Conclusion Stress MPI is useful for predicting cardiac events and may be performed in patients without chest pain if they have mildly impaired systolic LV function or LV asynergy. (Circ J 2006; 70: 762 - 767)

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Background The purpose of the present study was to investigate pregnancy-related changes in the maternal serum lipid profile and endothelial function. Methods and Results As part of the population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland, 57 pregnant Finnish women and 62 control women matched for age and smoking were examined throughout gestation. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined and concomitantly endothelium-dependent brachial artery flow mediated dilation (FMD) was measured by ultrasound. During pregnancy serum TC, LDL-C, HDL-C, TG and very-low-density lipoprotein cholesterol increased significantly when compared with the non-pregnant state (p<0.001 for each) and towards the end of pregnancy (p<0.001, p<0.001, p=0.007, p<0.001, p<0.001). FMD increased towards the end of pregnancy and there was a statistically significant direct correlation between gestational age and FMD% (r=0.345, p=0.010). Brachial artery diameter at rest and FMD% were negatively correlated in pregnant (r=-0.280, p=0.035) and non-pregnant women (r=-0.360, p<0.004). The univariate correlation analysis showed a direct correlation between maternal serum TC (r=0.333, p=0.012) and TG (r=0.366, p=0.006) and FMD%, whereas a negative non-significant correlation was found in non-pregnant women. In a multivariate model, vessel size (β=-0.436, p=0.001) and TG (β=0.502, p<0.001) were the most powerful predictors for FMD% in pregnancy, the influence of other lipids was non-significant. Conclusions In healthy pregnant women increased gestational age is associated with improved endothelium-dependent vasodilation responses regardless of concurrently appearing lipid changes. (Circ J 2006; 70: 768 - 772)

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Background Cold-water face immersion (FI) is known to produce physiological changes, including bradycardia, by stimulating the parasympathetic system. However, other factors such as sympathetic activity, intrapleural pressures, and changes in chemical mediators may also contribute to these changes. Methods and Results Eight healthy volunteers underwent a series of experiments designed to observe the effects of FI on heart rate and its variability, as detected using wavelet transformation. Each subject was instructed to bend over and put the entire face into an empty basin with and without breathing (protocols 1 and 2, respectively), and then perform FI in warm-water (protocols 3 and 4, respectively) and cold-water (protocols 5 and 6, respectively) while breathing and breath holding. Change in the R-R interval with FI was only significantly greater for protocol 6 than for the control procedure (protocol 1). Also, changes in the natural logarithm of high-frequency power with FI were significantly greater for protocols 5 and 6 than the protocol 1. Conclusions Bradycardia associated with cold-water FI is mainly attributed to cardiac vagal activity, which is independent of both the change in body position caused by bending over a basin and breath holding. (Circ J 2006; 70: 773 - 776)

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Background The Ca²⁺ regulatory proteins in the sarcoplasmic reticulum (SR) play a key role in the pathogenesis of heart failure. In the present study the effect of chronic β-receptor-stimulation on cardiac and SR functions was assessed, with or without angiotensin-II receptor antagonist treatment recently reported to have anti-β-adrenergic activity. Methods and Results Rats were treated with isoproterenol with (+) or without (-) candesartan (CAN) and then SR vesicles were isolated from the left ventricular muscle. Both Ca²⁺-uptake and the amount of SR Ca²⁺-ATPase were significantly lower in the CAN (-) group than in the shams, but those were almost normally restored in the CAN (+). Although the level of the protein kinase A (PKA)-phosphorylation of the SR Ca²⁺ release channel, known as the ryanodine receptor (RyR2), was elevated in the CAN (-), no Ca²⁺-leak was detected. However, SIN-1 (O₂ ^- donor) induced Ca²⁺-leak in the CAN (-) at a 10-fold lower dose than in the sham and CAN (+). In cardiomyocytes, SIN-1 decreased cell shortening and the peak Ca²⁺ transient and prolonged time from peak to 70% decline in CAN (-), again at 10-fold lower dose than in the sham and CAN (+). Conclusion Chronic β-receptor-stimulation did not induce any Ca²⁺-leak from the SR, whereas Ca²⁺-leak was easily induced when oxidative stress was applied to the PKA-phosphorylated RyR2. Candesartan not only improved Ca²⁺-uptake, but also prevented PKA-phosphorylation, rendering the SR less susceptible to Ca²⁺-leak. (Circ J 2006; 70: 777 - 786)

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Background Hypoxia caused by sleep apnea might be associated with an increased risk of cardiovascular events in subjects with metabolic syndrome. The aim of this study was to examine the effect of hypoxia on the left ventricular (LV) myocardium and evaluate the cardioprotective effect of an angiotensin-II receptor blocker (ARB) in diabetic rats. Methods and Results Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 30 weeks of age (n=30) were divided into 2 groups that were treated with vehicle or candesartan 0.2 mg · kg^-1 · day ^-1. The animals were housed in a hypoxic gas chamber (oxygen, 10.0±0.5%, mean ± standard deviation) for 2 weeks. Hypoxia increased right ventricular (RV) systolic pressure (hypoxia; 78±14 mmHg vs control; 22±5, p<0.05), but did not increase LV systolic pressure (131±23 mmHg vs 121±10). Hypoxia exacerbated the degeneration of cardiomyocytes, and accelerated the expression of hypoxia inducible factor-1α (HIF-1 α) and vascular endothelial growth factor (VEGF) in the myocardium. Treatment with ARB decreased RV and LV pressures (46±7 and 100±18 mmHg, respectively), suppressed the expression of HIF-1α and VEGF, and preserved the fine structure of the LV myocardium. Conclusions ARB exhibited cardioprotection under hypoxia, in part through the reduction of blood pressure and cytokine expression, in OLETF rats. Thus, ARB might be a potent agent for the treatment of diabetic patients with the complication of sleep apnea. (Circ J 2006; 70: 787 - 792)

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A 68-year-old female patient was referred for the evaluation of an incidentally detected asymptomatic cardiac mass. Imaging studies showed a 3.0×2.4 cm, well circumscribed, round, cystic mass with a calcified nodule that was attached to the lower rim of the fossa ovalis in the right atrium. Under cardiopulmonary bypass, the right atrium was opened to reveal a well circumscribed, dark bluish, pedunculated mass. Histologically, the specimen was a unilocular cyst lined by flattened endothelium, with peripheral fibrin clots and dystrophic calcification of the wall. Immunohistochemical staining of the lining cells was positive for cluster designation 34, which represents hematopoietic progenitor cell antigen. The final pathologic diagnosis was compatible with varix of the heart, which should be considered for a cystic mass with a calcified nodule located in the right atrium, near the lower rim of the fossa ovalis. (Circ J 2006; 70: 793 - 795)

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Coronary artery fistulas (CAF) are a rare anomaly in which there is communication between a coronary artery and a cardiac chamber or another vascular structure. A giant congenital CAF to the left brachial vein was identified clearly by multidetector computed tomography (MDCT) in an 84-year-old woman who presented with orthopnea and continuous murmur. Electrocardiogram was almost normal, but chest X-ray showed marked cardiomegaly with pulmonary congestion. Transthoracic echocardiography showed that the wall motion of the left ventricle (LV) was normal, but with an abnormal cavity behind the LV. CAF was suspected and coronary angiography revealed that the CAF originated from the right coronary artery (RCA), connected to the giant vessel. However, because the drainage site was not clearly detected, MDCT was performed and it became clear that the CAF originated from the RCA. The left circumflex artery flowed into the giant vessel, and drained to the left brachial vein. (Circ J 2006; 70: 796 - 799)

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Previous studies have shown that coronary stents have radial strength above the pressure induced by coronary artery spasm. This case report describes a stent deformity caused by coronary artery spasm during percutaneous coronary intervention. (Circ J 2006; 70: 800 - 801)

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