Background Although obesity is required for some criteria defining metabolic syndrome, clustering of other risk factors also indicates an increased risk of cardiovascular disease. Whether the relationship between cardiovascular risk factor clustering and medical expenditures differs with body mass index (BMI) requires investigation, especially in a population with a low prevalence of obesity such as that in Japan. Methods and Results A 10-year cohort study of 4,478 Japanese National Health Insurance beneficiaries aged 40-69 years in a community between 1990 and 2001 was carried out in the present study. The clustering of cardiovascular risk factors showed a positive and graded relationship to personal medical expenditures in participants who are overweight (BMI ≥25.0) and normal weight (BMI <25.0). The individual medical expenditures per month were 1.7-fold higher for participants with 2 or 3 risk factors and overweight than for those without these factors (26,782 vs 15,377 Japanese yen). Differences in the geometric means were similarly significant after adjustment for other confounding factors. However, the excess medical expenditures by risk clustering of normal weight categories within the total medical expenditures were higher than those of overweight categories because more participants were of normal weight. Conclusions Cardiovascular risk factor clustering and being overweight can be a useful predictor of medical expenditures in a Japanese population. (Circ J 2007; 71: 807 - 813)

View full abstract

Background The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. Methods and Results A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age ≥30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). Conclusion AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events. (Circ J 2007; 71: 814 - 819)

View full abstract

Background Although numerous studies have demonstrated a positive association of high-sensitivity C-reactive protein (CRP) with the incidence of coronary heart disease (CHD), little information exists regarding this issue in Japanese. Methods and Results The association between CRP and the Framingham Risk Score (FRS) was investigated in 2,523 middle-aged Japanese men without a medical history of CHD. CRP was significantly associated with this score obtained from all FRS factors. After dividing subjects into 4 categories of relative risk estimate for CHD, the geometric mean of CRP (mg/L) increased gradually with the CHD risk (below average: 0.39 [95% confidence interval, 0.37-0.41], average: 0.58 [0.50-0.67], moderately above average: 0.70 [0.57-0.86], high: 0.79 [0.58-1.09], trend p<0.001). However, it should be noted that the mean CRP concentration of the high-risk group was only 0.79 mg/L and a greater proportion (63.8%) of the high-risk subjects was in the low-risk range of CRP (<1 mg/L). Conclusions Circulating CRP well reflect the estimated CHD risk, indicating that CRP may be useful for coronary risk stratification in Japanese also. However, the details of the CRP level in Japanese must be investigated further by prospective studies to determine the Japanese-specific cutoff points for CHD risk evaluation. (Circ J 2007; 71: 820 - 825)

View full abstract

Background The efficacy and safety of nicorandil were evaluated in Chinese patients with stable angina pectoris (AP) in a double-blind, multicenter, active-controlled, randomized clinical trial. Methods and Results After a 2-week washout period, 232 patients with stable AP were randomized to receive either nicorandil (5 mg tid; 115 patients) or isosorbide mononitrate (ISMN: 20 mg bid; 117 patients) for 2 weeks. Exercise capacity, number of weekly anginal attacks, nitroglycerin (NTG) consumption, and safety were evaluated. Nicorandil and ISMN significantly prolonged the time to 1 mm ST-segment depression in an exercise tolerance test. Both drugs improved the total exercise time and the time to onset of chest pain. There was no significant difference between the 2 groups. Nicorandil significantly decreased the number of anginal attacks and NTG consumption. ISMN decreased the number of anginal attacks significantly; however, there was no significance in NTG consumption, and the ratio of anginal attack reduction was at least 50% was significantly higher with nicorandil. Nicorandil was well tolerated and there was no safety profile difference compared with ISMN. Thus, nicorandil may have equivalent or better antianginal effect than ISMN. Conclusions Nicorandil is beneficial as treatment for AP. (Circ J 2007; 71: 826 - 833)

View full abstract

Background Newly-diagnosed diabetes mellitus (DM) and impaired glucose tolerance are common among patients with acute myocardial infarction (AMI). However, its significance on long-term clinical outcomes in those patients remains unclear. The present study was designed to determine whether such abnormalities after AMI affect long-term clinical outcomes. Methods and Results Two-hundred and seventy-five AMI patients were prospectively enrolled. Eighty-five had diagnosed DM, while the other 190 did not. According to oral glucose tolerance tests at discharge, non-DM patients were divided into 2 groups: 78 patients with normal glucose tolerance and 112 patients with abnormal glucose tolerance. Patients were followed until they reached the primary endpoint: cardiovascular death or unplanned hospitalization due to major adverse cardiovascular events. The median follow-up period was 5.3 years. Kaplan-Meier survival curves for the abnormal glucose tolerance group were poorer than for normal glucose tolerance, and were equivalent to the pre-diagnosed DM group in prognosis (p<0.0005). Glucometabolic status was the strongest predictor for future cardiovascular events (hazard ratio to normal glucose tolerance; 2.65; confidence interval: 1.37-5.15; p=0.004 in abnormal glucose tolerance and 3.27:1.68-6.38; p=0.0005 in DM). Conclusions Abnormal glucose tolerance in patients with AMI is a major risk factor for future cardiovascular events and may critically distinguish high-risk individuals. (Circ J 2007; 71: 834 - 841)

View full abstract

Background Endothelial lipase (EL) is a major determinant of high-density lipoprotein-cholesterol (HDL-C) metabolism and promotes monocytes recruitment. The local expression of EL could influence atherogenesis directly, in addition to its systemic role in HDL metabolism. The EL gene has a common 584C/T polymorphism, but it is unclear whether this polymorphism is associated with HDL-C levels or acute myocardial infarction (AMI). Methods and Results A case - control study of 107 AMI patients and 107 control subjects was conducted. T allele frequency was lower in the AMI group than in controls (0.18 vs 0.26, p<0.05). No significant association was found between the 584C/T polymorphism and HDL-C levels. Multivariate regression analyses showed that the association of the T allele with AMI was statistically significant and independent of other risk factors when age, sex, hypertension, hypercholesterolemia, and diabetes mellitus were included in the analyses (odds ratio (OR), 0.52; 95% confidence interval (95% CI) 0.28-0.98; p=0.04). However, when smoking status was included, the association of the T allele with AMI did not remain statistically significant (OR, 0.61; 95% CI 0.32-1.18; p=0.14). Conclusions The 584C/T polymorphism of the EL gene was associated with AMI independently of HDL-C levels and thus may be involved in the pathogenesis of AMI. (Circ J 2007; 71: 842 - 846)

View full abstract

Background Thus far, the outcome and effect of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery on the quality of life of octogenarian patients has not been accurately assessed in Japan. Methods and Results A retrospective analysis of the outcome of invasive coronary revascularization in 130 elderly patients (age, ≥80 years) with ischemic coronary disease was carried out. Their current quality of life was determined by the Seattle Angina Questionnaire. Although the in-hospital death rate was relatively high (21.6% after PCI and 14.3% after CABG surgery), the long-term outcome of the patients who did not die during the in-hospital period after the PCI/CABG surgery was acceptable (5-year survival rate, >60%). All domains of the questionnaire received a favorable score from a majority of the survivors, irrespective of the treatment they received. Conclusions The quality of life and longevity of the octogenarian patients following extensive invasive revascularization for ischemic coronary artery disease were satisfactory. (Circ J 2007; 71: 847 - 854)

View full abstract

Background Percutaneous coronary intervention (PCI) is considered an excellent alternative treatment for unprotected left main coronary artery (ULMCA) stenoses. Most PCIs for ULMCA stenoses are performed via the transfemoral approach. The feasibility and safety of the transradial approach for this particular entity are unknown. The present study assessed the feasibility, safety and 1-year outcomes of the transradial approach for stenting of ULMCA stenoses. Methods and Results Of 131 consecutive patients who underwent coronary stenting for ULMCA stenoses, 113 patients (86.3%) received stenting using the transradial approach. All 113 procedures were performed with 6 or 7 French (Fr) catheters except 1 procedure requiring an 8 Fr guiding catheter for directional atherectomy. The technical success rate was 100%, and angiographic success was achieved in 96 patients (85.9%). Two patients had local hematoma (1.8%), and no procedure-related deaths, Q-wave myocardial infarction, repetitive PCI, stroke or emergent coronary artery bypass graft surgery during hospitalization were noted. One (0.9%) in-hospital cardiac death occurred due to ventricular tachyarrhythmia. More than half of our patients stayed in hospital by ≤3 days. The 1-year target lesion revascularization and cardiac death rate were 14.2% and 3.5%, respectively. Conclusions This investigation demonstrated the feasibility, safety and accepted short-term clinical outcomes of transradial stenting for ULMCA stenosis. This procedure may offer a feasible alternative to the transfemoral approach. (Circ J 2007; 71: 855 - 861)

View full abstract

Background The effect of adjunctive heparin for primary angioplasty in patients with ST-elevation myocardial infarction (STEMI) is not well established, so the authors investigated the effect of early heparin administration in the emergency room (ER) on initial patency of the infarct-related artery (IRA) and on the clinical outcome in STEMI patients. Methods and Results One hundred and twenty consecutive patients who presented with STEMI less than 12 h from pain onset and who were eligible for primary percutaneous coronary intervention were allocated to an early heparin group (heparin administered in ER) or a late heparin group (heparin administered after angiography). In the early heparin group, unfractionated heparin (60 U/kg bolus IV, then 14 U · kg^-1 · h^-1 IV infusion) or enoxaparin (1 mg/kg bolus SC) were administered 144±95 min before angioplasty. No significant differences in baseline characteristics were observed between the early heparin group (n=56) and the late heparin group (n=64). However, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade in the IRA was significantly different between the 2 groups (frequency of TIMI 0/1/2/3; 48/4/7/41% vs 70/8/11/11%, early vs late respectively, p=0.002). TIMI 2 or 3 flow was significantly more frequent in the early heparin group than in the late heparin group (48% vs 22%, p=0.002). However, no significant differences were noted between the 2 groups in terms of in-hospital major adverse cardiac events (7% vs 11%, p=0.472) and TIMI major bleeding (2% vs 3%, p=0.639). Conclusions In STEMI patients, early heparin therapy administered in the ER improves coronary patency, despite not reaching clinical benefit. (Circ J 2007; 71: 862 - 867)

View full abstract

Background Resistin is an adipocyte-secreted hormone. The relationship between circulating resistin concentrations and atherosclerotic coronary artery disease (CAD) in type 2 diabetic patients, if any, remains poorly understood. Serum resistin concentrations were investigated in type 2 diabetic patients with CAD (DMCAD), and compared with the concentrations in diabetics patients without CAD (diabetes mellitus, DM). Whether resistin levels are associated with increased restenosis rates in diabetic patients with CAD after successful coronary stenting was also investigated. Methods and Results Fasting serum resistin, adiponectin, and leptin concentrations were measured in 45 DMCAD patients and 47 DM controls. The percutaneous coronary intervention study included 70 DMCAD patients, who underwent elective and successful coronary bare metal stent (BMS) implantation for the treatment of de novo lesions. Serum resistin concentrations were higher in the DMCAD patients than in the DM controls (5.75±3.21 vs 2.53±2.47 ng/ml, mean ± SEM, p<0.001), and these differences were persistent regardless of age or body mass index. Insulin resistance indices, as assessed via homeostasis model assessment (HOMA-IR) correlated significantly with resistin concentrations (r=0.4, p<0.001). Resistin was an independent factor, and was associated with DMCAD in the multivariate analysis. In the percutaneous coronary intervention study, HOMA-IR was not associated with subsequent restenosis rates after BMS implantation in DMCAD patients. Pre-procedural serum resistin concentrations were higher in restenosis group than in the patients without restenosis. Conclusions Serum resistin may prove to be a useful biological marker for CAD and restenosis in patients with type 2 DM. (Circ J 2007; 71: 868 - 873)

View full abstract

Background No prior studies have clarified the utility and efficacy of unipolar recording for identifying successful sites for atrioventricular junction (AVJ) ablation. Methods and Results Thirty-six patients underwent radiofrequency (RF) AVJ ablation for drug-resistant atrial fibrillation (AF) or AF/flutter. AVJ ablation was performed with either bipolar (Bi-group; n=18) or unipolar plus bipolar recording (Uni-group; n=18). In the Uni-group, the primary parameter used to select ablation sites was a QS or rS morphology of the His bundle unipolar recording. There was no significant difference between the 2 groups for the bipolar electrogram characteristics at the successful ablation site. However, in the Uni-group, the procedure time and fluoroscopy duration were shorter (both p<0.05), and the total number of RF energy applications less (p<0.05) than in the Bi-group. In the Uni-group, unipolar His bundle recordings could be assessed in 26 (76%) of 34 RF energy applications: Complete atrioventricular block was obtained at 15 (83%) of 18 sites with QS morphology and in 3 (37%) of 8 sites with rS morphology on the unipolar His bundle recording. Conclusions AVJ ablation can be achieved more efficiently and with fewer RF energy applications when guided by unipolar recordings than by bipolar recordings alone. (Circ J 2007; 71: 874 - 879)

View full abstract

Background P-wave dispersion (PD), a measure of heterogeneity of atrial refractoriness, is defined as the difference between the minimum (P min) and maximum P-wave (P max) durations on standard 12-lead electrocardiography (ECG). Increase in PD shows the intra-atrial and inter-atrial non-uniform conduction. In the present study the evaluation of the effect of diabetes mellitus (DM) on PD in patients without coronary artery disease and hypertension was carried out. Methods and Results Seventy-six diabetic patients who had no coronary artery disease or hypertension (group 1; mean age 48±9) and 40 healthy volunteer individuals (group 2; mean age 46±13) were enrolled in the study. After obtaining 12-lead surface ECG of all cases, P max and P min P-wave durations were measured and the differences between them were taken as PD (PD=P max-P min). Left atrium diameter, left ventricular end systolic and end diastolic diameters were measured and left ventricular ejection fraction was determined by echocardiography. Pulse wave mitral flow velocities were measured from the apical 4-chamber view. Mitral early diastolic velocity (E), late diastolic velocity (A), E/A, E deceleration time and isovolumetric relaxation time were determined. In comparison of the 2 groups there was no statistically significant difference among age, sex, systolic and diastolic blood pressure, resting heart rate and body mass index of the cases. Although PD and P max were significantly higher in diabetic patients, there was no difference between P min values (33±12 vs 28±10, p=0.02; 99±12 vs 93±10, p=0.011; 66±9 vs 65±10, p=NS; respectively). Conclusions DM might increase PD even without ischemia, hypertension and left ventricular hypertrophy. (Circ J 2007; 71: 880 - 883)

View full abstract

Background The clinical features of patients with the dilated phase of hypertrophic cardiomyopathy (DHCM) may resemble those of patients with dilated cardiomyopathy (DCM); that is, systolic dysfunction and left ventricular dilatation. Myocardial flow reserve (MFR) is impaired in patients with nonischemic cardiomyopathy, and the reduced MFR may be related to poor prognosis. Several studies report that the mortality rate for patients with DHCM is higher than for DCM, but the difference between these 2 cardiomyopathies is still unclear. The purpose of this study was to assess the MFR of these 2 cardiomyopathies, using ¹⁵O-water positron emission tomography (PET) to elucidate their differences. Methods and Results In total 30 patients were investigated: 23 with DCM (Group A) and 7 with DHCM (Group B). All those who were in a stable condition underwent cardiac catheterization. Myocardial blood flow (MBF) at rest and under ATP infusion was measured by ¹⁵O-water PET, and the MFR was calculated. There were no significant differences in the hemodynamics of the 2 groups. The mean MFR in DHCM was significantly lower than that in DCM (1.49±0.31 vs 2.62±1.08; p=0.042), whereas MBF at rest did not differ (DCM vs DHCM: 0.66±0.20 vs 0.49±0.05 ml · min^-1 · g^-1; NS). The MFR in both Group A and B was significantly decreased compared with the normal controls (MFR in normal controls: 5.15±1.64, p=0.00015, 0.00013, respectively). Conclusions These results suggest that impaired vasodilatation (ie, dysfunction of the microcirculation) is more severe in patients with DHCM than in patients with DCM, even though patients' characteristics and hemodynamics do not differ. (Circ J 2007; 71: 884 - 890)

View full abstract

Background The assessment of patients with chest pain is an important step to make a diagnosis and clinical decision. Coronary flow reserve (CFR) can be used for the screening of significant coronary stenosis. However, the feasibility and limitation of CFR in those patients remains unknown. Methods and Results A total of 100 patients with chest pain were examined. CFR was measured in all 3 major coronary arteries by using transthoracic Doppler echocardiography (TTDE). Coronary angiography was performed 1 to 3 days after TTDE. CFR in all 3 major coronary arteries could be measured in 83 (83%) of 100 patients. The echo-contrast agent was useful in 32 of 49 patients who had unclear color Doppler images. When CFR <2.0 was regarded as the cut-off point, the overall agreement rate between CFR and the results of coronary angiography was 83% (69 of the 83 patients). In addition, CFR could predict the presence of coronary artery disease satisfactorily (sensitivity 85%, specificity 81%, positive predictive value 89%, negative predictive value 93%). Conclusions TTDE seems to be a promising tool for screening patients with chest pain. Moreover, an echo-contrast agent seems to be an effective and supportive tool for patients who have poor visualization of coronary flow. (Circ J 2007; 71: 891 - 896)

View full abstract

Background A transmitral E/septal Ea ratio ≥15 is a predictor of adverse outcome in cardiac disease, so it was hypothesized that a septal E/Ea ≥15 would predict the risk of adverse outcome, including sustained ventricular tachycardia (VT), cardiac arrest, implantable cardioverter defibrillator (ICD) discharge, or sudden death (SD) in patients with hypertrophic cardiomyopathy (HCM). Methods and Results The study group comprised 96 consecutive patients with HCM (median age 53 years) who completed all noninvasive tests for risk stratification. The endpoint of the study was defined as death, cardiac arrest, documented sustained VT, or ICD-discharge. The median follow-up was 20.6 months. All patients were alive at the end of follow-up, although 8 patients had reached the endpoint during the study period. The variables that were predictive of adverse clinical outcome were family history of premature SD (p=0.03), syncope (p<0.001), maximum wall thickness ≥3 cm (p=0.02), and septal E/Ea ≥15 (p<0.001). In a stepwise multivariable model the only independent prognostic indicator was a septal E/Ea ≥15 (relative risk 0.26, 95% confidence interval 0.2-0.58, p<0.001). The cumulative event-free survival rate was 78.9% in patients with septal E/Ea ≥15, and 100% in patients with septal E/Ea <15 (p=0.0003). Conclusions Septal E/Ea ≥15 predicts patients with HCM who are at risk of sustained VT, cardiac arrest, ICD-discharge, or SD. (Circ J 2007; 71: 897 - 903)

View full abstract

Background Adenosine has been available for use in myocardial perfusion single-photon emission computed tomography (SPECT) in Japan since 2005. The purpose of this study was to evaluate the safety of and tolerance to thallium-201 myocardial perfusion SPECT with intravenous adenosine infusion in Japanese patients with suspected coronary artery disease. Methods and Results Two hundred and six consecutive patients who underwent an adenosine infusion (120 μg · kg^-1 · min^-1) SPECT at Sumitomo Besshi Hospital (Niihama, Japan) were investigated. The effects of adenosine infusion were monitored for each patient. A coronary angiography was performed in 81 patients. Adenosine infusion significantly decreased blood pressure and increased heart rate. Adverse reactions were observed in 161 patients (78.2%). Most reactions were transient, disappearing soon after the termination of adenosine infusion. No serious adverse reactions, such as acute myocardial infarction or death, occurred. Adenosine infusion was terminated in 3 patients (1.5%) because of near syncope or sustained 2:1 atrioventricular block. Electrocardiographic changes occurred in 15 patients (7.3%). Self-assessed scoring after SPECT showed that the patients were very tolerant (74.6% of 177 patients) of adenosine infusion myocardial SPECT. The sensitivity and specificity were 75.0% and 69.7%, respectively. Conclusions Adenosine infusion myocardial SPECT is safe and well tolerated in the Japanese population, despite the frequent occurrence of minor adverse reactions. (Circ J 2007; 71: 904 - 910)

View full abstract

Background The ability to evaluate coronary stenosis using multi-detector computed tomography (MDCT) has been well discussed. In contrast, several studies demonstrated that the plaque burden measured by intravascular ultrasound (IVUS) has a relationship to the risk of cardiovascular events. the accuracy of MDCT was studied to determine plaque and vessel size compared with IVUS. Methods and Results Fifty-six proximal lesions (American College of Cardiology/American Heart Association classification: segment 1, 5, 6) from 33 patients were assessed using MDCT and IVUS. The plaque and vessel area were measured from the cross-sectional image using both MDCT and IVUS. Eight coronary artery lesions with motion artifacts and heavily calcified plaques were excluded from the analysis. The vessel and lumen size evaluated using MDCT were closely correlated with those evaluated by IVUS (R²=0.614, 0.750 respectively). Furthermore, there was a strong correlation between percentage plaque area assessed by MDCT and IVUS (R²=0.824). Conclusion MDCT can noninvasively quantify coronary atherosclerotic plaque with good correlation compared with IVUS in patients with atherosclerosis. (Circ J 2007; 71: 911 - 914)

View full abstract

Background Plasma renin activity (PRA) may be limited to angiotensinogen levels, which decrease in patients with heart failure (HF) because of liver congestion. Methods and Results To evaluate whether the plasma active renin concentration (ARC) is a more useful prognostic predictor than PRA, the plasma levels of ARC, PRA, angiotensin II, aldosterone, brain natriuretic peptide (BNP), norepinephrine, and hemodynamic parameters were measured in 214 consecutive HF patients who were already taking angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB). Median follow-up period was 1,197 days. Of the clinical variables, including pulmonary capillary wedge pressure, right atrial pressure, left ventricular ejection fraction, and neurohumoral factors, only high plasma levels of log ARC (p<0.0001) and log BNP (p=0.0009), but not log PRA, were significant independent prognostic predictors. Log ARC/PRA ratio was significantly higher in nonsurvivors than in survivors. Log ARC/PRA significantly correlated with pulmonary capillary wedge pressure (r=0.305, p<0.0001), right atrial pressure (r=0.222, p=0.0011), and log BNP (r=0.242, p=0.0004). Conclusions Plasma ARC is superior to PRA and a high plasma ARC is an independent prognostic predictor in HF patients who are already receiving ACEI or ARB. (Circ J 2007; 71: 915 - 921)

View full abstract

Background Reduced exercise capacity may be related to decreased redistribution of blood flow from the non-exercising tissues to the exercising skeletal muscle in patients with mild chronic heart failure (CHF). Methods and Results In the present study 14 patients with mild CHF and 10 healthy subjects (N) underwent symptom-limited multistage-ergometer exercise, during which forearm vascular resistance (FVR), cardiac index (CI), systemic vascular resistance index (SVRI), and oxygen uptake (VO₂) were measured non-invasively using the plethysmograph, impedance, and respiratory gas analysis methods, respectively. The VO₂ and CI at peak exercise were lower (p<0.01 each), and SVRI and FVR at both rest and peak exercise were higher in the CHF group than in N. However, both the percent increase in FVR and percent decrease in SVRI from the resting state to peak exercise were lower in CHF than N, and both of them correlated with not only peak VO₂, but also the corresponding resting value of FVR and SVRI (p<0.01 each). Conclusions Redistribution of blood flow from the non-exercising tissues to the working skeletal muscles, which may participate in exercise capacity, can be blunted in CHF. The decreased vasoconstrictive response in the non-exercising tissues is intimately related to the increased resting vascular tone in CHF. (Circ J 2007; 71: 922 - 928)

View full abstract

Background Clinical markers to predict adverse outcome have not yet been established for patients with preserved left ventricular (LV) systolic function. The present study was designed to examine whether carboxy-terminal telopeptide of type I collagen (ICTP), a marker of collagen degradation, is useful for determining the prognosis of such patients. Methods and Results Serum levels of ICTP were measured at admission in 156 consecutive patients hospitalized for chronic heart failure (CHF). Patients were divided into 2 groups based on the LV ejection fraction (LVEF): reduced LV systolic function group (LVEF <50%, n=92) and preserved LV systolic function group (LVEF ≥50%, n=64). In preserved LV systolic function group, cardiac event-free rates were significantly lower in high ICTP group than in low ICTP group (p<0.001). The area under the receiver operating characteristic curve of ICTP in the preserved LV systolic function group was markedly larger than that in the reduced LV systolic function group. Cox multivariate analysis also revealed that ICTP was an independent predictor of cardiac events in the preserved LV systolic function group. Conclusion Serum ICTP level is highly reliable for risk stratifying CHF patients with preserved LV systolic function. (Circ J 2007; 71: 929 - 935)

View full abstract

Background Sustained tachycardia causes left ventricular (LV) systolic dysfunction leading to heart failure (HF), which is widely known as "tachycardia-induced cardiomyopathy (TIC)", but its prevalence and prognosis in Japanese remain unclear. Methods and Results Of 213 consecutive patients with HF associated with atrial fibrillation (AF) requiring hospitalization (n=213) between January 1999 and December 2004, and 104 (83 males, 67±12.6 years) were identified as not having any structural heart disease. Of them 41 (39%) had a normal LV ejection fraction (LVEF) at the initial admission, and the remaining patients fell into 2 groups: those with rapid (<6 months) normalization of the LVEF after AF management (presumed TIC, 30 patients, 29%) and those with persistent LV systolic dysfunction (dilated cardiomyopathy (DCM), 33 patients, 32%). Although the B-type natriuretic peptide value and LVEF did not differ between the 2 groups, the LV size on admission was significantly smaller in the TIC group (LV end-diastolic dimension (LVDd) 57.6±7.2, LV end-systolic dimension (LVDs) 49.4±8.0) than in the DCM group (LVDd 63.4 ±8.8, LVDs 55.3±9.6, p<0.05). During a follow-up period of 42.1±21.2 months, cardiac death and recurrent HF hospitalization were significantly less frequent in the TIC group than in the DCM group. Conclusions In AF-associated HF requiring hospitalization, TIC is the presumed cause in approximately one-third of patients without any previously known structural heart disease. That particular group is characterized by a relatively smaller LV and better prognosis under medical treatment. (Circ J 2007; 71: 936 - 940)

View full abstract

Background In vivo redundancy of pro-inflammatory cytokines results in a vicious cycle of systemic inflammatory response syndrome and low cardiac output syndrome (LOS). The purpose of this study was to elucidate the influence of peritoneal fluid (PF) drainage on cytokine dynamics in vivo and the significance of early induction for infants with LOS. Methods and Results Seven infants, who underwent early PF drainage to manage LOS after repair of complex heart defects under cardiopulmonary bypass, were enrolled. The serum and PF levels of the pro- and antiinflammatory cytokines, interleukin (IL)-6, -8, -10 and tumor necrosis factor (TNF)-α, were measured during the perioperative period. Clinical outcomes were observed simultaneously. There were no cases of early or late death, or infectious complications. Drainage volume of PF peaked just after operation, and decreased completely. The amount of proinflammatory cytokines in the PF increased for 3 days after operation. Of the proinflammatory cytokines in the PF IL-6 increased the earliest and cleared the fastest. The amount of cleared IL-8 and TNF-α peaked on the 3rd postoperative day and resembled the course of C-reactive protein (CRP). Serum levels of CRP and proinflammatory cytokines in patients with PF drainage decreased significantly more than those without PF drainage. Conclusions Early initiation of PF drainage is useful in the postoperative critical care of infants with LOS by improving cytokine dynamics in vivo, although there are differences between the severity of patients undergoing PF drainage and those who do not. (Circ J 2007; 71: 941 - 947)

View full abstract

Background The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activation exists in patients with CCHD. Methods and Results Platelet P-selectin as a marker of platelet activation, plasma thrombomodulin level and protein C activity as markers of anticoagulant activity of the endothelium and thrombin - antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma thrombomodulin level (1.1±0.9 vs 2.2±0.3 FU/ml) and protein C activity (71.1±29.8 vs 117.8±24.8%) were significantly lower in patients with CCHD as compared with the control subjects. The levels of plasma TAT (255±811 vs 1.9±0.9 ng/ml) and P-selectin on platelets (6.3 ±4.5 vs 3.3±0.3 mean fluorescence intensity) were significantly higher in the patients with CCHD than in the controls. Four of the CCHD patients who experienced thromboembolic events had elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients without thromboembolic events. Conclusion Platelet activation exists in patients with CCHD and it may play an important role in the thromboembolic events in CCHD. (Circ J 2007; 71: 948 - 953)

View full abstract

Background The relationships between flow reserves in coronary and peripheral circulation and their modification by statin therapy have not been assessed in the same patients, especially females. Methods and Results To assess the effect of pravastatin on both circulation, in 20 postmenopausal female patients with hypercholesterolemia but a low probability of coronary artery disease, the forearm blood flow reserve (FBFR) using the plethysmographic method and coronary flow velocity reserve (CFVR) by Doppler echocardiography were measured before, 4 and 8 weeks after starting the pravastatin and/or diet therapy. At baseline, CFVR and FBFR had a positive linear correlation (r=0.63, p<0.01) while each of them had a negative linear correlation (r=-0.53 to -0.63, p<0.05 each) with total or LDL-cholesterol levels. Four weeks after starting the pravastatin therapy when the decrease in total cholesterol reached a plateau, FBFR increased (p<0.05) by 38±14%, whereas CFVR did not. Such an increase in FBFR by pravastatin was related to the degree of total or LDL-cholesterol lowering. Conclusions In postmenopausal hypercholesterolemic women with a low probability of coronary artery disease, the cholesterol-lowering with pravastatin improved FBFR as early as 4 to 8 weeks after starting the therapy, whereas its effect on CFVR was unclear at that time. (Circ J 2007; 71: 954 - 961)

View full abstract

Background T cells are among the earliest cells to infiltrate the arterial intima during the initial stages of atherosclerosis. Alterations in the peripheral blood lymphocyte distribution might be associated with intensive lymphocytes extravasation and stimulation of atherosclerotic plaque development. Epidemiological data reveal that short-term postprandial hyperglycemia is a significant risk factor for coronary heart disease. Using a parameter that indicates recently-past acute hyperglycemia, 1,5-anhydro-D-glucitol (1,5-AG), the aim of the present study was to elucidate which alterations in peripheral blood T-lymphocytes, if any, are associated with acute hyperglycemia in patients with type 2 diabetes mellitus (DM) and, thus, might be involved in the progression of atherosclerosis. Methods and Results Measurement of fasting glucose level, glycated hemoglobin A_1c, 1,5-AG, lipid profile and lymphocyte receptors expression (CD3⁺, CD4⁺, CD8⁺, CD8⁺28⁺, CD⁺28 ^-) was performed in 97 patients with type 2 DM, 23 patients with coronary heart disease, and 15 healthy controls. The mean CD3⁺, CD4⁺, CD8⁺28 ^- and CD8⁺28⁺ lymphocyte counts were significantly higher in the DM patients than in both control groups. Multiple regression analysis revealed that CD4⁺ and CD8⁺28^- lymphocyte counts primarily were dependent on 1,5-anhydro-D-glucitol plasma levels. Conclusions These results suggest that acute hyperglycemia results in the progression of atherosclerosis in type 2 DM, at least in part through changes in CD4⁺ and CD8⁺28^- lymphocyte subsets. (Circ J 2007; 71: 962 - 967)

View full abstract

Background Valganciclovir (VGC) has recently been proved efficacious for the prophylaxis and treatment of cytomegalovirus (CMV) infection in transplant recipients. Leucopenia is a troublesome complication of VGC but the possible risk factors are unknown. Methods and Results Once a cardiac recipient's quantitative real-time CMV-polymerase chain reaction result showed positive, VGC was administered for 3 months. The 61 cardiac recipients enrolled in this study were divided into 2 groups: non-leucopenia group (n=29) and leucopenia group (n=32). The white blood cell (WBC) counts in the leucopenia group dropped approximately 55.6% in the first month after VGC therapy (pre-VGC WBC count: 5,544 cells/mm³ vs post-VGC WBC count: 2,460 cells/mm³, p<0.0001). The most significant difference between the 2 groups was body mass index (BMI, 23.04 vs 25.84, p=0.008), which was the impact factor of VGC-induced leucopenia. Conclusion Severe leucopenia may develop after VGC therapy in Chinese cardiac recipients, especially those with lower BMI. (Circ J 2007; 71: 968 - 972)

View full abstract

Background During both cardiac maturation and myopathy, elevated levels of circulating catecholamines coincide with alterations in impulse propagation. An in vitro model of cultured cardiomyocytes was used to study the effects of adrenergic stimulation on the conduction characteristics of immature heart cells. Methods and Results Neonatal rat cardiomyocytes were cultured on preparations designed to measure conduction velocity (CV). CV was measured on the same preparation twice at t=0 and at t=24 h. Under control conditions (n=7), CV at t=0 (30.9±1.9 cm/s) and t=24 (32.4±4.4 cm/s) was similar (p=0.70). Immunohistochemistry revealed expression of the gap junction proteins connexin (Cx) 40, Cx43 and Cx45, with Cx43 being highly predominant. Stimulation for 24 h with the β-adrenergic agonist isoproterenol (ISO) significantly increased CV from 28.0 ±2.0 cm/s at t=0 to 34.8±2.2 cm/s at t=24 (p=0.002, n=5). Microelectrode recordings showed a faster upstroke of the action potential (AP) of ISO-treated cells. Reverse transcribed-polymerase chain reactions (RT-PCR) showed that ISO increased expression of SCN5A and α_1c (α-subunit of the cardiac sodium and L-type calcium channel, respectively). Stimulation of cells with ISO did not induce alterations in distribution or expression of Cx40, Cx43 and Cx45 (both mRNA and protein), but slightly increased the phosphorylation of Cx43. Stimulation for 24 h with the α-adrenergic agonist phenylephrine did neither affect CV nor the expression of the connexin isoforms, SCN5A and α_1c. Conclusions Alpha- and β-adrenergic stimulation differently affect propagation of the electric impulse, which is primarily not caused by a differential effect on intercellular coupling. RT-PCR analysis and an enhanced AP upstroke velocity indicate a higher functional expression level of α_1c and SCN5A in β-adrenergic stimulated cells, which may explain the observed increase in CV. (Circ J 2007; 71: 973 - 981)

View full abstract

An 81-year-old woman with emotionally-induced takotsubo cardiomyopathy developed a fatal left ventricular (LV) apical rupture. During the hospitalization persistent ST-segment elevation with no electrocardiographic time evolution was observed on the ECG, characteristic for takotsubo cardiomyopathy. Histopathologically, transmural myocardial necrosis with hemorrhage was found at the rupture site, but there were foci of coagulation and contraction band necrosis with mononuclear lymphocyte infiltrations in other heart regions, and the intensity and distribution of these pathological changes corresponded to the distribution of the LV contraction abnormalities seen on ventriculography. The article concludes that: the LV functional disorder in takotsubo cardiomyopathy may be caused by distracted foci of coagulation and contraction band necrosis in the myocardium; contraction band necrosis (a sign of catecholamine cardiotoxicity) may reflect the sympathetic hyperactivity in this disease; persistent myocardial damage expressed by persistent ST-segment elevation without an electrocardiographic time evolution should be carefully observed with sequential echocardiographic examinations because of the possibility of cardiac rupture. (Circ J 2007; 71: 982 - 985)

View full abstract

A mass was identified in the atrial septum by clinical imaging in a patient who had multiple large lipomas of the skin. Multislice computed tomography and magnetic resonance imaging indicated that the interatrial mass was a fatty infiltration. In order to discriminate the myocardial lesion from myxoma and other benign conditions and malignant tumors, percutaneous transvenous biopsy was performed. Microscopic examination demonstrated the cardiac mass to be lipomatous hypertrophy of the interatrial septum (LHIS), and the skin lesions, simple lipomas. The LHIS is itself a rare condition, and its development in patients having multiple ponderous lipomas, or lipomatosis, could not be found in a previous report. This may be the first published case of LHIS, which likely represents cardiac involvement of lipomatosis. (Circ J 2007; 71: 986 - 989)

View full abstract

Background It is important to differentiate takotsubo cardiomyopathy from other types of transient ventricular dysfunction. These guidelines, resulting from a workshop sponsored by the Ministry of Health, Labour, and Welfare, Idiopathic Cardiomyopathy Research Committee, outline the steps necessary for diagnosis of takotsubo cardiomyopathy. Methods and Results The survey was conducted by mailing a questionnaire to the researchers of the 203 institutions that had made presentations on this disease at scientific meetings of the Japanese Circulation Society from November 1989 to October 2002. The questionnaires were sent and collected on January 10, 2003. Based on the results of the questionnaire, the first edition of the guidelines for diagnosis of takotsubo cardiomyopathy was prepared and evaluated at the 2003 group meeting of the Research Committee. Out of 33 researchers in Japan who had published research papers on this disease, 21 responded to the request and provided their opinions. The guidelines were revised and were approved at the 2004 group meeting. Conclusions This summary provides standard guidelines for patients with takotsubo cardiomyopathy. (Circ J 2007; 71: 990 - 992)

View full abstract